197 results on '"Anil A. Joy"'
Search Results
2. Access to Neoadjuvant Pertuzumab for HER2 Positive Breast Cancer in Canada: A Dilemma Increasingly Difficult to Explain
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Daniel Rayson, Sonal Gandhi, Anil A. Joy, Christine Brezden-Masley, Karen A. Gelmon, Sandeep Sehdev, David Cescon, and Stephen Chia
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breast cancer ,HER2 positive ,neoadjuvant ,pertuzumab ,access ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The addition of pertuzumab to neoadjuvant trastuzumab and chemotherapy for women with early-stage, high-risk, HER2+ breast cancer has been observed to lead to higher pathologic complete response rates (pCR), and improved event-free survival compared to trastuzumab and chemotherapy alone. Based on available data, neoadjuvant pertuzumab is recommended by ESMO, ASCO, and NICE as well as by a Canadian Consensus Guideline Group. We discuss the implications for Canadian patients with HER2+ early breast cancer due to a second and final negative funding decision by the Canadian Agency for Drugs and Technologies in Health (CADTH) related to neoadjuvant pertuzumab. This decision will have adverse impacts for up to 1 in 6 women receiving neoadjuvant therapy for high-risk HER2+ breast cancer, due to suboptimal pCR rates and higher risks of invasive breast cancer recurrent events, resulting in the need for more toxic adjuvant therapy.
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- 2022
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3. Effect of palbociclib plus endocrine therapy on time to chemotherapy across subgroups of patients with hormone receptor‒positive/human epidermal growth factor receptor 2‒negative advanced breast cancer: Post hoc analyses from PALOMA-2 and PALOMA-3
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Hope S. Rugo, Seock-Ah Im, Anil A. Joy, Yaroslav Shparyk, Janice M. Walshe, Bethany Sleckman, Sherene Loi, Kathy Puyana Theall, Sindy Kim, Xin Huang, Eustratios Bananis, Reshma Mahtani, Richard S. Finn, and Véronique Diéras
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Advanced breast cancer ,Chemotherapy ,Palbociclib ,Progression-free survival ,Safety ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: Previous analyses from the PALOMA-2 and PALOMA-3 studies showed that palbociclib (PAL) plus endocrine therapy (ET) prolongs time to first subsequent chemotherapy (TTC) versus placebo (PBO) plus ET in the overall population of patients with hormone receptor‒positive/human epidermal growth factor receptor 2‒negative (HR+/HER2−) advanced breast cancer (ABC). Here, we evaluated TTC in relevant patient subgroups. Methods: These post hoc analyses evaluated TTC by subgroup using data from 2 randomized, phase 3 studies of women with HR+/HER2− ABC. In PALOMA-2, postmenopausal patients previously untreated for ABC were randomized 2:1 to receive PAL (125 mg/day, 3/1-week schedule) plus letrozole (LET; 2.5 mg/day; n = 444) or PBO plus LET (n = 222). In PALOMA-3, premenopausal or postmenopausal patients whose disease had progressed after prior ET were randomized 2:1 to receive PAL (125 mg/day, 3/1-week schedule) plus fulvestrant (FUL; 500 mg; n = 347) or PBO plus FUL (n = 174). Results: First subsequent chemotherapy was received by 35.5% and 56.2% in PALOMA-2 and PALOMA-3 after progression on palbociclib plus ET or placebo plus ET. Across all subgroups analyzed, the median progression-free survival (PFS) was longer in the PAL plus ET arm than the PBO plus ET arm. TTC was longer with PAL plus ET versus PBO plus ET across the same patient subgroups in both studies. Conclusions: Across all subgroups, PAL plus ET versus PBO plus ET had longer median PFS and resulted in prolonged TTC in both the PALOMA-2 and PALOMA-3 studies.Pfizer Inc (NCT01740427, NCT01942135).
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- 2022
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4. Virtual or In-Person: A Mixed Methods Survey to Determine Exercise Programming Preferences during COVID-19
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Kirsten Suderman, Tara Skene, Christopher Sellar, Naomi Dolgoy, Edith Pituskin, Anil A. Joy, Susan Nicole Culos-Reed, and Margaret L. McNeely
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cancer ,exercise ,eHealth ,implementation ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
A survey was conducted to identify barriers and facilitators to engaging in virtual and in-person cancer-specific exercise during COVID-19. A theory-informed, multi-method, cross-sectional survey was electronically distributed to 192 individuals with cancer investigating preferences towards exercise programming during COVID-19. Respondents had previously participated in an exercise program and comprised two groups: those who had experience with virtual exercise programming (‘Virtual’) and those who had only taken part in in-person exercise (‘In-Person’). Quantitative data were summarized descriptively. Qualitative data were thematically categorized using framework analysis and findings were mapped to an implementation model. The survey completion response rate was 66% (N = 127). All respondents identified barriers to attending in-person exercise programming during COVID-19 with concerns over the increased risk of viral exposure. Virtual respondents (n = 39) reported: (1) feeling confident in engaging in virtual exercise; and (2) enhanced motivation, accessibility and effectiveness as facilitators to virtual exercise. In-Person respondents (n = 88) identified: (1) technology as a barrier to virtual exercise; and (2) low motivation, accessibility and exercise effectiveness as barriers towards virtual exercise. Sixty-six percent (n = 58) of In-Person respondents reported that technology support would increase their willingness to exercise virtually. With appropriately targeted support, perceived barriers to accessing virtual exercise—including motivation, accessibility and effectiveness—may become facilitators. The availability of technology support may increase the engagement of individuals with cancer towards virtual exercise programming.
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- 2022
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5. Documenting patients’ and providers’ preferences when proposing a randomized controlled trial: a qualitative exploration
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Devesh Oberoi, Cynthia Kwok, Yong Li, Cindy Railton, Susan Horsman, Kathleen Reynolds, Anil A. Joy, Karen Marie King, Sasha Michelle Lupichuk, Michael Speca, Nicole Culos-Reed, Linda E. Carlson, and Janine Giese-Davis
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Breast cancer ,Cancer survivors ,Transition of care ,Cancer care coordination ,Telephone survivorship clinic ,Oncology nurse ,Medicine (General) ,R5-920 - Abstract
Abstract Background With advances in cancer diagnosis and treatment, women with early-stage breast cancer (ESBC) are living longer, increasing the number of patients receiving post-treatment follow-up care. Best-practice survivorship models recommend transitioning ESBC patients from oncology-provider (OP) care to community-based care. While developing materials for a future randomized controlled trial (RCT) to test the feasibility of a nurse-led Telephone Survivorship Clinic (TSC) for a smooth transition of ESBC survivors to follow-up care, we explored patients’ and OPs’ reactions to several of our proposed methods. Methods We used a qualitative study design with thematic analysis and a two-pronged approach. We interviewed OPs, seeking feedback on ways to recruit their ESBC patients for the trial, and ESBC patients, seeking input on a questionnaire package assessing outcomes and processes in the trial. Results OPs identified facilitators and barriers and offered suggestions for study design and recruitment process improvement. Facilitators included the novelty and utility of the study and simplicity of methods; barriers included lack of coordination between treating and discharging clinicians, time constraints, language barriers, motivation, and using a paper-based referral letter. OPs suggested using a combination of electronic and paper referral letters and supporting clinicians to help with recruitment. Patient advisors reported satisfaction with the content and length of the assessment package. However, they questioned the relevance of some questions (childhood trauma) while adding questions about trust in physicians and proximity to primary-care providers. Conclusions OPs and patient advisors rated our methods for the proposed trial highly for their simplicity and relevance then suggested changes. These findings document processes that could be effective for cancer-patient recruitment in survivorship clinical trials.
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- 2022
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6. Efficacy and safety of palbociclib in patients with estrogen receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer with preexisting conditions: A post hoc analysis of PALOMA-2
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Karen Gelmon, Janice M. Walshe, Reshma Mahtani, Anil A. Joy, Meghan Karuturi, Patrick Neven, Dongrui Ray Lu, Sindy Kim, Patrick Schnell, Eustratios Bananis, and Lee Schwartzberg
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Advanced breast cancer ,Preexisting condition ,Palbociclib ,Progression-free survival ,Safety ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Objective: In the PALOMA-2 trial, palbociclib in combination with letrozole prolonged progression-free survival (PFS) and exhibited an acceptable safety profile in patients with estrogen receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer (ABC). This post hoc analysis of PALOMA-2 evaluated the efficacy and safety of palbociclib plus letrozole in patients with preexisting conditions grouped by Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class (SOC). Methods: Postmenopausal patients without prior treatment for ABC were randomized 2:1 to receive palbociclib (125 mg/d on a 3 weeks on/1 week off schedule) plus letrozole (2.5 mg/d, continuous) or placebo plus letrozole. Patients were grouped by the following MedDRA SOC preexisting conditions: gastrointestinal, musculoskeletal, metabolic, and vascular/cardiac. Median PFS was estimated by the Kaplan-Meier method, and treatment emergent adverse events (AEs) were compared between treatment arms within each preexisting condition subgroup. Results: At baseline, 276 (41.4 %) patients had preexisting gastrointestinal disorders, 390 (58.6 %) had musculoskeletal disorders, 259 (38.9 %) had metabolic disorders, and 382 (57.4 %) had vascular/cardiac disorders. Baseline characteristics were similar between subgroups and between each arm within subgroups. Regardless of baseline preexisting condition, palbociclib plus letrozole prolonged PFS compared with placebo plus letrozole. Treatment-emergent AEs associated with palbociclib plus letrozole and dose modifications due to AEs were similar across preexisting condition subgroups. Conclusion: This post hoc analysis of PALOMA-2 demonstrated a favorable effect of palbociclib on PFS and a safety profile consistent with previous observations, regardless of underlying preexisting condition. Pfizer Inc (NCT01740427).
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- 2021
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7. Rationale and design of the Diet Restriction and Exercise-induced Adaptations in Metastatic breast cancer (DREAM) study: a 2-arm, parallel-group, phase II, randomized control trial of a short-term, calorie-restricted, and ketogenic diet plus exercise during intravenous chemotherapy versus usual care
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Amy A. Kirkham, Karen King, Anil A. Joy, André B. Pelletier, John R. Mackey, Kelvin Young, Xiaofu Zhu, Judith Meza-Junco, Sanraj K. Basi, Julie Price Hiller, Tina Brkin, Bonnie Michalowski, Edith Pituskin, D. Ian Paterson, Kerry S. Courneya, Richard B. Thompson, and Carla M. Prado
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Breast cancer ,Metastatic ,Chemotherapy ,Exercise ,Ketogenic ,Calorie restriction ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background An underlying cause of solid tumor resistance to chemotherapy treatment is diminished tumor blood supply, which leads to a hypoxic microenvironment, dependence on anaerobic energy metabolism, and impaired delivery of intravenous treatments. Preclinical data suggest that dietary strategies of caloric restriction and low-carbohydrate intake can inhibit glycolysis, while acute exercise can transiently enhance blood flow to the tumor and reduce hypoxia. The Diet Restriction and Exercise-induced Adaptations in Metastatic Breast Cancer (DREAM) study will compare the effects of a short-term, 50% calorie-restricted and ketogenic diet combined with aerobic exercise performed during intravenous chemotherapy treatment to usual care on changes in tumor burden, treatment side effects, and quality of life. Methods Fifty patients with measurable metastases and primary breast cancer starting a new line of intravenous chemotherapy will be randomly assigned to usual care or the combined diet and exercise intervention. Participants assigned to the intervention group will be provided with food consisting of 50% of measured calorie needs with 80% of calories from fat and ≤ 10% from carbohydrates for 48–72 h prior to each chemotherapy treatment and will perform 30–60 min of moderate-intensity cycle ergometer exercise during each chemotherapy infusion, for up to six treatment cycles. The diet and exercise durations will be adapted for each chemotherapy protocol. Tumor burden will be assessed by change in target lesion size using axial computed tomography (primary outcome) and magnetic resonance imaging (MRI)-derived apparent diffusion coefficient (secondary outcome) after up to six treatments. Tertiary outcomes will include quantitative MRI markers of treatment toxicity to the heart, thigh skeletal muscle, and liver, and patient-reported symptoms and quality of life. Exploratory outcome measures include progression-free and overall survival. Discussion The DREAM study will test a novel, short-term diet and exercise intervention that is targeted to mechanisms of tumor resistance to chemotherapy. A reduction in lesion size is likely to translate to improved cancer outcomes including disease progression and overall survival. Furthermore, a lifestyle intervention may empower patients with metastatic breast cancer by actively engaging them to play a key role in their treatment. Trial registration ClinicalTrials.gov, NCT03795493 , registered 7 January, 2019.
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- 2021
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8. A multi-centre study comparing granulocyte-colony stimulating factors to antibiotics for primary prophylaxis of docetaxel-cyclophosphamide induced febrile neutropenia
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Mark Clemons, Dean Fergusson, Anil A. Joy, Kednapa Thavorn, Judith Meza-Junco, Julie Price Hiller, John Mackey, Terry Ng, Xiaofu Zhu, Mohammed F.K. Ibrahim, Marta Sienkiewicz, Deanna Saunders, Lisa Vandermeer, Gregory Pond, Bassam Basulaiman, Arif Awan, Lacey Pitre, Nancy A. Nixon, Brian Hutton, and John F. Hilton
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Docetaxel-cyclophosphamide ,Breast cancer ,Febrile neutropenia ,G-CSF ,Ciprofloxacin ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: Primary febrile neutropenia (FN) prophylaxis with ciprofloxacin or granulocyte-colony stimulating factors (G-CSF) is recommended with docetaxel-cyclophosphamide (TC) chemotherapy for early-stage breast cancer (EBC). A pragmatic randomised trial compared the superiority of G-CSF to ciprofloxacin and a cost-utility analysis were conducted. Methods: EBC patients receiving TC chemotherapy were randomised to ciprofloxacin or G-CSF. The primary outcome was a composite of FN and non-FN treatment-related hospitalisation. Secondary outcomes included; rates of FN, non-FN treatment-related hospitalisation, chemotherapy dose reductions/delays/discontinuations. Primary analysis was performed with the intention to treat population. Cost-utility analyses were conducted from the Canadian public payer perspective. Results: 458 eligible patients were randomised: 228 to ciprofloxacin and 230 to G-CSF. For the primary endpoint there was non-statistically significant difference (Risk difference = −6.7%, 95%CI = −13.5%–0.1%, p = 0.061) between ciprofloxacin patients (46,20.2%) and G-CSF (31,13.5%). Patients receiving ciprofloxacin were more likely to experience FN (36/228, 15.8% vs 13/230, 5.7%) than patients receiving G-CSF (p
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- 2021
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9. Phase angle is associated with muscle health and cardiorespiratory fitness in older breast cancer survivors
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Bruna Ramos Da Silva, Amy A. Kirkham, Katherine L. Ford, Mark J. Haykowsky, D. Ian Paterson, Anil A. Joy, Edith Pituskin, Richard Thompson, and Carla M. Prado
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Nutrition and Dietetics ,Endocrinology, Diabetes and Metabolism - Published
- 2023
10. The 'Begin Exploring Fertility Options, Risks and Expectations' (BEFORE) decision aid: development and alpha testing of a fertility tool for premenopausal breast cancer patients.
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Brittany Speller, Kelly Metcalfe, Erin D. Kennedy, Marcia Facey, Ellen Greenblatt, Adena S. Scheer, Ellen Warner, Anil Abraham Joy, Frances C. Wright, and Nancy N. Baxter
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- 2019
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11. Rapid atrophy of cardiac left ventricular mass in patients with non‐small cell carcinoma of the lung
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Seyyed Mohammad Reza Kazemi‐Bajestani, Harald Becher, Charles Butts, Naveen S. Basappa, Michael Smylie, Anil Abraham Joy, Randeep Sangha, Andrea Gallivan, Peter Kavsak, Quincy Chu, and Vickie E. Baracos
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Cardiac atrophy ,Cancer ,Cachexia ,Left ventricular mass ,Diseases of the musculoskeletal system ,RC925-935 ,Human anatomy ,QM1-695 - Abstract
Abstract Background Cancer is a systemic catabolic condition affecting skeletal muscle and fat. We aimed to determine whether cardiac atrophy occurs in this condition and assess its association with cardiac function, symptoms, and clinical outcomes. Methods Treatment naïve metastatic non‐small cell lung cancer patients (n = 50) were assessed prior to and 4 months after commencement of carboplatin‐based palliative chemotherapy. Methods included echocardiography for left ventricular mass (LVM) and LV function [LV ejection fraction, global longitudinal strain (GLS), diastolic function], computed tomography to quantify skeletal muscle and total adipose tissue, Eastern Cooperative Oncology Group Performance Status (ECOG‐PS), validated questionnaires for dyspnoea and fatigue, plasma biomarkers, tumour response to therapy, and overall survival. Results During 112 ± 6 days, the median change in LVM was −8.9% [95% confidence interval (95% CI) −10.8 to −4.8, P < 0.001]. Quartiles of LVM loss were −20.1%, −12.9%, −4.8%, and +5.5%. Losses of muscle, adipose tissue, and LVM were frequently concurrent; LVM loss > median value was associated with loss of skeletal muscle [odds ratio (OR) = 4.5, 95% CI: 1.4–14.8, P=0.01] and loss of total adipose tissue (OR = 10.0, 95% CI: 2.7–36.7, P < 0.001). LVM loss was associated with decreased GLS (OR = 6.6, 95% CI: 1.9–22.7, P=0.003) but not with LV ejection fraction or diastolic function. In the population overall, plasma levels of C‐reactive protein (P=0.008), high sensitivity troponin T (hs‐TnT) (P=0.03), and galectin‐3 (P=0.02) increased over time, while N‐terminal pro B‐type natriuretic peptide and hs‐cTnI did not change over time. C‐reactive protein was the only biomarker associated with LVM loss but at the univariate level only. Independent predictors of LVM loss were prior weight loss (adjusted OR = 10.2, 95% CI: 2.2–46.9, P=0.003) and tumour progression (adjusted OR = 14.6, 95% CI: 1.4–153.9, P=0.02). LVM loss was associated with exacerbations of fatigue (OR = 6.6, 95% CI: 1.9–22.7, P=0.003), dyspnoea (OR = 9.3, 95% CI: 2.4–35.8, P
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- 2019
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12. Time-Restricted Eating in Breast Cancer Survivors: Effects on Body Composition and Nutritional Status
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Bruna Ramos Da Silva, Amy A. Kirkham, Katherine L. Ford, Mark J. Haykowsky, D. Ian Paterson, Anil A. Joy, Edith Pituskin, Richard Thompson, and Carla M. Prado
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Cancer Research ,Nutrition and Dietetics ,Oncology ,Medicine (miscellaneous) - Published
- 2023
13. Implementation of weekday <scp>time‐restricted</scp> eating to improve metabolic health in breast cancer survivors with overweight/obesity
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Amy A. Kirkham, Katherine L. Ford, Bruna Ramos Da Silva, Jordan Topolnyski, Carla M. Prado, Anil A. Joy, D. Ian Paterson, Normand Boulé, Edith Pituskin, Mark J. Haykowsky, and Richard B. Thompson
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Nutrition and Dietetics ,Endocrinology ,Endocrinology, Diabetes and Metabolism ,Medicine (miscellaneous) - Published
- 2023
14. Positive progress: current and evolving role of immune checkpoint inhibitors in metastatic triple-negative breast cancer
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Christine E. Simmons, Christine Brezden-Masley, Joy McCarthy, Deanna McLeod, and Anil Abraham Joy
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: Triple-negative breast cancer (TNBC) represents an aggressive breast cancer subtype with historically poor overall outcomes, due primarily to a lack of effective targeted agents. Chemotherapy has been the primary treatment approach, although immune checkpoint inhibitors (ICIs) are currently being investigated to improve patient outcomes. This review examines the clinical implications of current evidence on the use of ICIs for the treatment of metastatic TNBC. Methods: Our systematic search identified two phase III and five phase I/II trials reporting on the efficacy of ICIs used as monotherapy or combined with chemotherapy for the treatment of metastatic TNBC. Results: The phase III IMpassion 130 trial showed a significant improvement in median progression-free survival in the intent-to-treat (net 1.7 months, p = 0.002) and PD-L1-positive populations (net 2.5 months, p
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- 2020
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15. Chemotherapy-induced weight gain in early-stage breast cancer: a prospective matched cohort study reveals associations with inflammation and gut dysbiosis
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John Walker, Anil Abraham Joy, Larissa J. Vos, Trevor H. Stenson, John R. Mackey, Juan Jovel, Dina Kao, Karen L. Madsen, and Gane Ka-Shu Wong
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General Medicine - Abstract
Background Early-stage breast cancer patients treated with chemotherapy risk the development of metabolic disease and weight gain, which can result in increased morbidity and reduced quality of life in survivorship. We aimed to analyze changes within the gastrointestinal microbiome of early-stage breast cancer patients treated with and without chemotherapy to investigate a potential relationship between dysbiosis, a systemic inflammatory response, and resultant anthropomorphic changes. Methods We undertook an a priori analysis of serially collected stool and plasma samples from 40 patients with early-stage breast cancer who underwent adjuvant endocrine therapy only, adjuvant chemotherapy only, or both. Gut microbiota were assessed by metagenomic comparison of stool samples following deep sequencing. Inflammatory biomarkers were evaluated by proteomic analysis of plasma and measurement of fecal calprotectin. Body composition was investigated by dual-energy X-ray absorptiometry to determine biomass indices. Results As opposed to treatment with endocrine therapy only, chemotherapy resulted in statistically and clinically significant weight gain and an increase in the android to gynoid ratio of fat distribution. Patients treated with chemotherapy gained an average of 0.15% total mass per month, as opposed to a significantly different loss of 0.19% in those patients who received endocrine-only therapy. Concurrently, a twofold increase in fecal calprotectin occurred after chemotherapy that is indicative of interferon-dependent inflammation and evidence of colonic inflammation. These anthropomorphic and inflammatory changes occurred in concert with a chemotherapy-dependent effect on the gut microbiome as evidenced by a reduction in both the abundance and variety of microbial species. Conclusions We confirm the association of chemotherapy treatment with weight gain and potential deleterious anthropometric changes and suggest that alterations of bacterial flora may contribute to these phenomena through the induction of systemic inflammation. Consequently, the gut microbiome may be a future target for intervention in preventing chemotherapy-dependent anthropometric changes.
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- 2023
16. CCTG BR34: A Randomized Phase 2 Trial of Durvalumab and Tremelimumab With or Without Platinum-Based Chemotherapy in Patients With Metastatic NSCLC
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Phillipe Joubert, Anil A. Joy, M. Mates, Ming-Sound Tsao, Glenwood D. Goss, Natasha B. Leighl, Keyue Ding, Normand Blais, Swati Kulkarni, Janet Dancey, Punam Rana, Scott A. Laurie, Martin R. Stockler, Penelope A. Bradbury, Sunil Yadav, Francisco E. Vera-Badillo, David M. Hwang, Craig Underhill, Christopher Lee, Andrea Hiltz, and Brett G.M. Hughes
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Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,Lung Neoplasms ,Durvalumab ,medicine.medical_treatment ,Antibodies, Monoclonal, Humanized ,Chemoimmunotherapy ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Clinical endpoint ,Humans ,Lung cancer ,Platinum ,Chemotherapy ,business.industry ,Antibodies, Monoclonal ,Combination chemotherapy ,Immunotherapy ,medicine.disease ,business ,Tremelimumab ,medicine.drug - Abstract
First-line therapy for patients with metastatic NSCLC includes checkpoint inhibitor monotherapy, dual checkpoint inhibition, or combination with chemotherapy. We compared outcomes with combination chemoimmunotherapy versus dual checkpoint inhibition as first-line treatment for patients with metastatic NSCLC.This open-label, randomized clinical trial was conducted at 44 sites in Canada and Australia. Patients with treatment-naive, metastatic NSCLC without sensitizing EGFR or ALK alterations were randomized (1:1) to receive treatment with durvalumab plus tremelimumab with or without platinum-doublet chemotherapy. The primary end point was overall survival (OS). Secondary end points were progression-free survival, overall response rate, and safety.A total of 301 patients were randomized. Median OS was 16.6 months (95% confidence interval [CI]: 12.6-19.1) with chemotherapy plus immunotherapy and 14.1 months (95% CI: 10.6-18.3) with immunotherapy (hazard ratio = 0.88, 90% CI: 0.67-1.16, p = 0.46). Median progression-free survival with chemotherapy plus immunotherapy was 7.7 months (95% CI: 5.5-8.5) and 3.2 months (95% CI: 2.7-5.1) with immunotherapy (hazard ratio = 0.67, 95% CI: 0.52-0.88). The overall response rate with chemoimmunotherapy was 42.4% and 29.3% with immunotherapy (adjusted OR = 1.69, 95% CI: 1.04-2.76). The percentage of patients with grade 3 or higher adverse events was 82% in the chemotherapy plus immunotherapy group and 70% in the immunotherapy group. Exploratory analyses of programmed death-ligand 1 expression and blood-based tumor mutation burden revealed no differential treatment effect on OS.The addition of chemotherapy to durvalumab plus tremelimumab in the first-line treatment of stage IV NSCLC did not improve survival compared with durvalumab plus tremelimumab alone. Further study is warranted to identify patients that benefit from initial immunotherapy alone versus combination chemotherapy plus immunotherapy as first-line treatment.
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- 2022
17. Abstract OT2-11-06: SERENA-4: A Phase III comparison of AZD9833 (camizestrant) plus palbociclib, versus anastrozole plus palbociclib, for patients with ER-positive/HER2-negative advanced breast cancer who have not previously received systemic treatment for advanced disease
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Fabrice André, Seock-Ah Im, Patrick Neven, Richard D Baird, Johannes Ettl, Matthew P Goetz, Erika Hamilton, Hiroji Iwata, Zefei Jiang, Anil Abraham Joy, Vincent Haddad, Andrew Walding, Manuel Selvi Miralles, Cynthia Huang Bartlett, and Antonio Llombart-Cussac
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Cancer Research ,Oncology - Abstract
Background: More than two thirds of patients with advanced breast cancer (ABC) have estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2−) tumors. In most countries, current standard-of-care first-line treatments include an aromatase inhibitor or fulvestrant, a selective ER degrader, combined with cyclin-dependent kinase 4/6 inhibitors. Concurrent use of luteinizing hormone-releasing hormone agonists is recommended for men and premenopausal women with ABC. Nevertheless, almost all ABCs eventually become resistant to endocrine therapy and the disease is incurable in these cases. New therapies are needed to combat endocrine therapy resistance, maintain patient health-related quality-of-life, and delay the need for chemotherapy. AZD9833 (camizestrant) is a highly potent, next-generation selective ER degrader and pure ER antagonist that has demonstrated anticancer properties across a range of preclinical models, including those with ER-activating mutations (Scott et al, AACR 2020). A Phase I dose-escalation and expansion study (SERENA-1) has demonstrated that AZD9833 is well tolerated and has a promising antitumor activity when administered alone or in combination with the cyclin-dependent kinase 4/6 inhibitor palbociclib (Baird et al, SABCS 2020). SERENA-4 (NCT04711252) is a randomized, multicenter, double-blind, Phase III trial to evaluate the safety and efficacy of AZD9833 in combination with palbociclib for patients with ER+/HER2− ABC who have not received systemic treatment in the advanced disease setting. Methods: SERENA-4 will enroll 1342 patients with de novo or recurrent ER+/HER2− ABC who have not previously received systemic treatment for their locoregionally recurrent or metastatic disease. Patients with recurrent disease must have received adjuvant aromatase inhibitor or tamoxifen therapy for at least 24 months without relapse. Patients will be randomized 1:1 to receive oral treatment with either (a) AZD9833 75 mg once daily, palbociclib 125 mg once daily for 21 days followed by 7 days off treatment and a placebo for anastrozole 1 mg once daily or (b) anastrozole 1 mg once daily, palbociclib (same as active arm) and a placebo for AZD9833 75 mg once daily. Men and premenopausal women will also receive a luteinizing hormone-releasing hormone agonist. The primary endpoint is progression-free survival (PFS; up to 5 years). Secondary endpoints include overall survival (up to 8 years), second PFS, time to chemotherapy, objective response rate, and changes in health-related quality-of-life measures. Enrollment began in January 2021. As of 02 July 2021, the number of open sites is 57 across 15 countries. Acknowledgments: We thank Julia Mawer, PhD, of Oxford PharmaGenesis, Oxford, UK, for providing medical writing support funded by AstraZeneca Funding: The SERENA-4 trial is funded and overseen by AstraZeneca. © 2021 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2021 ASCO Annual Meeting. All rights reserved. Citation Format: Fabrice André, Seock-Ah Im, Patrick Neven, Richard D Baird, Johannes Ettl, Matthew P Goetz, Erika Hamilton, Hiroji Iwata, Zefei Jiang, Anil Abraham Joy, Vincent Haddad, Andrew Walding, Manuel Selvi Miralles, Cynthia Huang Bartlett, Antonio Llombart-Cussac. SERENA-4: A Phase III comparison of AZD9833 (camizestrant) plus palbociclib, versus anastrozole plus palbociclib, for patients with ER-positive/HER2-negative advanced breast cancer who have not previously received systemic treatment for advanced disease [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-11-06.
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- 2022
18. Time-Restricted Eating to Reduce Cardiovascular Risk Among Older Breast Cancer Survivors
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Amy A. Kirkham, Katherine L. Ford, Jordan Topolnyski, Bruna Ramos Da Silva, D. Ian Paterson, Carla M. Prado, Anil A. Joy, Normand G. Boulé, Edith Pituskin, Mark J. Haykowsky, and Richard B. Thompson
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Oncology ,Cardiology and Cardiovascular Medicine - Published
- 2022
19. Efficacy and safety of palbociclib in patients with estrogen receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer with preexisting conditions: A post hoc analysis of PALOMA-2
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Reshma Mahtani, Janice M. Walshe, Eustratios Bananis, Meghan Sri Karuturi, D. Lu, Sindy T. Kim, Patrick Schnell, Anil A. Joy, Karen A. Gelmon, Patrick Neven, and Lee S. Schwartzberg
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Oncology ,medicine.medical_specialty ,Pyridines ,Receptor, ErbB-2 ,MedDRA ,Estrogen receptor ,Breast Neoplasms ,Palbociclib ,Placebo ,Piperazines ,Internal medicine ,Post-hoc analysis ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Progression-free survival ,Adverse effect ,Preexisting condition ,RC254-282 ,Science & Technology ,business.industry ,Letrozole ,Obstetrics & Gynecology ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,General Medicine ,Receptors, Estrogen ,OLDER WOMEN ,Surgery ,Female ,Original Article ,Advanced breast cancer ,Safety ,COMORBIDITY ,business ,Life Sciences & Biomedicine ,medicine.drug - Abstract
Objective In the PALOMA-2 trial, palbociclib in combination with letrozole prolonged progression-free survival (PFS) and exhibited an acceptable safety profile in patients with estrogen receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer (ABC). This post hoc analysis of PALOMA-2 evaluated the efficacy and safety of palbociclib plus letrozole in patients with preexisting conditions grouped by Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class (SOC). Methods Postmenopausal patients without prior treatment for ABC were randomized 2:1 to receive palbociclib (125 mg/d on a 3 weeks on/1 week off schedule) plus letrozole (2.5 mg/d, continuous) or placebo plus letrozole. Patients were grouped by the following MedDRA SOC preexisting conditions: gastrointestinal, musculoskeletal, metabolic, and vascular/cardiac. Median PFS was estimated by the Kaplan-Meier method, and treatment emergent adverse events (AEs) were compared between treatment arms within each preexisting condition subgroup. Results At baseline, 276 (41.4 %) patients had preexisting gastrointestinal disorders, 390 (58.6 %) had musculoskeletal disorders, 259 (38.9 %) had metabolic disorders, and 382 (57.4 %) had vascular/cardiac disorders. Baseline characteristics were similar between subgroups and between each arm within subgroups. Regardless of baseline preexisting condition, palbociclib plus letrozole prolonged PFS compared with placebo plus letrozole. Treatment-emergent AEs associated with palbociclib plus letrozole and dose modifications due to AEs were similar across preexisting condition subgroups. Conclusion This post hoc analysis of PALOMA-2 demonstrated a favorable effect of palbociclib on PFS and a safety profile consistent with previous observations, regardless of underlying preexisting condition. Pfizer Inc (NCT01740427)., Highlights • Preexisting conditions can affect the safety and efficacy of breast cancer therapies. • This is a post hoc analysis of patients with preexisting conditions from PALOMA-2. • Palbociclib prolonged median PFS, regardless of preexisting condition. • Within each treatment arm, AEs were similar regardless of preexisting condition.
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- 2021
20. A multi-centre study comparing granulocyte-colony stimulating factors to antibiotics for primary prophylaxis of docetaxel-cyclophosphamide induced febrile neutropenia
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Julie A. Price Hiller, Nancy A. Nixon, Anil A. Joy, Bassam Basulaiman, John Hilton, Terry L. Ng, Mohammed F.K. Ibrahim, Dean Fergusson, Marta Sienkiewicz, Arif Awan, Brian Hutton, Mark Clemons, Lisa Vandermeer, John R. Mackey, Deanna Saunders, Xiaofu Zhu, Gregory R. Pond, Judith Meza-Junco, Lacey D. Pitre, and Kednapa Thavorn
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Canada ,medicine.medical_specialty ,medicine.drug_class ,medicine.medical_treatment ,Febrile neutropenia ,Population ,Antibiotics ,Breast Neoplasms ,Docetaxel ,G-CSF ,03 medical and health sciences ,Breast cancer ,0302 clinical medicine ,Ciprofloxacin ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Granulocyte Colony-Stimulating Factor ,medicine ,Clinical endpoint ,Humans ,030212 general & internal medicine ,education ,Cyclophosphamide ,RC254-282 ,Chemotherapy ,education.field_of_study ,Intention-to-treat analysis ,Docetaxel-cyclophosphamide ,business.industry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,General Medicine ,medicine.disease ,Anti-Bacterial Agents ,3. Good health ,030220 oncology & carcinogenesis ,Female ,Original Article ,Surgery ,business ,Granulocytes ,medicine.drug - Abstract
Background Primary febrile neutropenia (FN) prophylaxis with ciprofloxacin or granulocyte-colony stimulating factors (G-CSF) is recommended with docetaxel-cyclophosphamide (TC) chemotherapy for early-stage breast cancer (EBC). A pragmatic randomised trial compared the superiority of G-CSF to ciprofloxacin and a cost-utility analysis were conducted. Methods EBC patients receiving TC chemotherapy were randomised to ciprofloxacin or G-CSF. The primary outcome was a composite of FN and non-FN treatment-related hospitalisation. Secondary outcomes included; rates of FN, non-FN treatment-related hospitalisation, chemotherapy dose reductions/delays/discontinuations. Primary analysis was performed with the intention to treat population. Cost-utility analyses were conducted from the Canadian public payer perspective. Results 458 eligible patients were randomised: 228 to ciprofloxacin and 230 to G-CSF. For the primary endpoint there was non-statistically significant difference (Risk difference = −6.7%, 95%CI = −13.5%–0.1%, p = 0.061) between ciprofloxacin patients (46,20.2%) and G-CSF (31,13.5%). Patients receiving ciprofloxacin were more likely to experience FN (36/228, 15.8% vs 13/230, 5.7%) than patients receiving G-CSF (p, Highlights • Primary febrile neutropenia (FN) prophylaxis is indicated for docetaxel-cyclophosphamide (TC) chemotherapy. • In this multicentre trial 458 breast cancer patients receiving TC chemotherapy were randomised to ciprofloxacin or to G-CSF. • For the primary endpoint of FN and non-FN treatment-related hospitalizations, G-CSF was not superior over ciprofloxacin. • While there were reduced FN rates with G-CSF, the incremental cost-effectiveness ratio was C$1,760,796 per one QALYWALY gained.
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- 2021
21. Cost-Effectiveness Analysis of 12-Versus 4-Weekly Administration of Bone-Targeted Agents in Patients with Bone Metastases from Breast and Castration-Resistant Prostate Cancer
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Carol Stober, Mihaela Mates, Terry L. Ng, Olexiy Aseyev, Mark Clemons, Ahwon Jeong, Lisa Vandermeer, Kednapa Thavorn, Anil A. Joy, Gregory R. Pond, Dean Fergusson, Phillip S. Blanchette, and Megan M. Tu
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Male ,Oncology ,Canada ,medicine.medical_specialty ,Cost effectiveness ,Cost-Benefit Analysis ,Bone Neoplasms ,Article ,03 medical and health sciences ,Prostate cancer ,breast cancer ,0302 clinical medicine ,Breast cancer ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,cost-effectiveness ,RC254-282 ,bone metastasis ,business.industry ,zoledronate ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Bone metastasis ,Cancer ,denosumab ,Cost-effectiveness analysis ,prostate cancer ,medicine.disease ,Clinical trial ,Prostatic Neoplasms, Castration-Resistant ,pamidronate ,Denosumab ,030220 oncology & carcinogenesis ,Quality-Adjusted Life Years ,business ,medicine.drug - Abstract
A cost–utility analysis was performed based on the Rethinking Clinical Trials (REaCT) bone-targeted agents (BTA) clinical trial that compared 12-weekly (once every 12 weeks) (n = 130) versus 4-weekly (once every 4 weeks) (n = 133) BTA dosing for metastatic breast and castration-resistant prostate (CRPC) cancer. Using a decision tree model, we calculated treatment and symptomatic skeletal event (SSE) costs as well as quality-adjusted life-years (QALYs) for each treatment option. Deterministic and probabilistic sensitivity analyses were performed to assess the robustness of the study findings. The total cost of BTA treatment in Canadian dollars (C$) and estimated QALYs was C$8965.03 and 0.605 QALY in the 4-weekly group versus C$5669.95 and 0.612 QALY in the 12-weekly group, respectively. De-escalation from 4-weekly to 12-weekly BTA reduces cost (C$3293.75) and improves QALYs by 0.008 unit, suggesting that 12-weekly BTA dominates 4-weekly BTA in breast and CRPC patients with bone metastases. Sensitivity analysis suggests high levels of uncertainty in the cost-effectiveness findings. De-escalation of bone-targeted agents is cost-effective from the Canadian public payer’s perspective.
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- 2021
22. Feasibility of Implementing Cancer-Specific Community-Based Exercise Programming: A Multi-Centre Randomized Trial
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Margaret L. McNeely, Kirsten Suderman, Janice L. Yurick, Kathryn Nishimura, Christopher Sellar, Paula A. Ospina, Edith Pituskin, Harold Lau, Jacob C. Easaw, Matthew B. Parliament, Anil A. Joy, and S. Nicole Culos-Reed
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Cancer Research ,Oncology ,cancer ,exercise ,implementation ,randomized controlled trial - Abstract
Background: There is growing recognition of the importance of reporting preliminary work on the feasibility of a trial. The present study aimed to assess the feasibility of (1) a proposed fitness testing battery, and (2) processes related to the implementation of cancer-specific exercise programming in a community setting. Methods/Design: A randomized controlled implementation feasibility trial was performed in advance of a large-scale implementation study. Eligible participants within 18 months of a cancer diagnosis were randomized to immediate or delayed community-based exercise at YMCA locations in Calgary and Edmonton, Canada for an 8-week period. The primary outcome for the trial was the feasibility of the physical fitness testing battery, defined as a 70% or greater completion rate across the 24-week study period. The Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework was used to evaluate processes related to implementation of the exercise program across the two sites. Results: Eighty participants were recruited, 73 (91%) completed the 8-week trial, and 68 (85%) completed the 16- and 24-week follow-ups. Sixty participants (75%) completed the full physical fitness test battery at each time point, and 59 (74%) completed the patient-reported outcome measures. Statistically significant between-group differences were found in favor of the exercise group for functional aerobic capacity, upper and lower extremity strength, and symptoms. Differences were found between the sites, however, in completion rates and processes related to program implementation. Discussion: Findings suggest the need for minor adaptations to the physical fitness battery and outcome measures to better fit the community context. While findings support feasibility, context-specific challenges related to implementation processes were identified.
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- 2022
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23. Abstract PS10-14: Efficacy and safety of palbociclib (PAL) in patients (pts) with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) with preexisting conditions: A post hoc analysis of PALOMA-2
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Janice M. Walshe, Patrick Schnell, Patrick Neven, D. Lu, Reshma Mahtani, Eustratios Bananis, Lee S. Schwartzberg, Karen A. Gelmon, Meghan Sri Karuturi, Anil A. Joy, and Sindy T. Kim
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Advanced breast ,Estrogen receptor ,Cancer ,Palbociclib ,medicine.disease ,Preexisting Conditions ,Internal medicine ,Post-hoc analysis ,medicine ,In patient ,business ,Human Epidermal Growth Factor Receptor 2 - Abstract
Background: In the PALOMA-2 trial, PAL + letrozole (LET) significantly prolonged progression-free survival (PFS) vs placebo (PBO) + LET in pts with ER+/HER2– ABC. This post hoc analysis assessed efficacy and safety of PAL + LET in pts from PALOMA-2 with baseline preexisting conditions grouped by Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class (SOC). Methods: Postmenopausal pts with ER+/HER2– ABC received PAL (125 mg/d, 3/1 schedule) + LET (2.5 mg/d, continuous) or PBO + LET. Pts were grouped by the following MedDRA SOC preexisting conditions: Gastrointestinal, Musculoskeletal, Metabolism, and Vascular/Cardiac. Baseline characteristics, PFS, and safety were assessed. Results: At baseline, 41.4% of pts had preexisting gastrointestinal disorders, 58.6% musculoskeletal disorders, 38.9% metabolism disorders, and 57.4% vascular/cardiac disorders. Baseline characteristics were similar between treatment arms within each subgroup and also between subgroups. Within each subgroup, ≥40% of pts also had ≥1 of the other coexisting conditions. Median PFS (mPFS) was significantly longer with PAL + LET vs PBO + LET regardless of preexisting condition (Table). In general, adverse events (AEs) were more frequent with PAL + LET in all subgroups; neutropenia was most common. Within each treatment arm, AEs and dose modifications due to AEs were similar regardless of preexisting condition. Conclusion: PAL + LET showed prolonged PFS and a consistent safety profile regardless of baseline preexisting condition in pts with ER+/HER2– ABC. Clinical trial identification: Pfizer Inc (NCT01740427) TablePreexisting ConditionPAL + LETPBO + LETPAL + LET vs PBO + LETnmPFS (95% CI)nmPFS (95% CI)HR (95% CI)P ValueGastrointestinal17627.6 (17.5–33.1)10013.6 (11.0–18.5)0.57 (0.42–0.78) Citation Format: Karen Gelmon, Janice M Walshe, Reshma Mahtani, Anil A Joy, Meghan Karuturi, Patrick Neven, Dongrui Ray Lu, Sindy Kim, Patrick Schnell, Eustratios Bananis, Lee Schwartzberg. Efficacy and safety of palbociclib (PAL) in patients (pts) with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) with preexisting conditions: A post hoc analysis of PALOMA-2 [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-14.
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- 2021
24. Abstract P5-02-27: Serum thymidine kinase activity as a prognostic marker in women with metastatic breast cancer treated with two different schedules of palbociclib plus second-line endocrine therapy within the CCTG MA38 trial
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Amelia McCartney, Chiara Biagioni, Bingshu Chen, Lois Shepherd, Karen Gelmon, Anil A. Joy, Wendy Parulekar, Mattias Bergqvist, Ilenia Migliaccio, Angela Leo, Matteo Benelli, Emanuela Risi, Erica Moretti, Luca Livraghi, Laura Biganzoli, and Luca Malorni
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Cancer Research ,Oncology - Abstract
Background: Thymidine kinase-1 is a cell proliferation marker downstream of the CDK4/6 pathway, whose activity can be measured in serum to reflect tumor proliferation. The CDK4/6 inhibitor palbociclib (P) is approved for the treatment of patients (pts) with hormone receptor positive metastatic breast cancer (MBC) in first or second line endocrine-based treatment settings. Approximately 10-15% of pts exhibit de novo resistance to P, with circulating levels of thymidine kinase activity (TKa) previously shown as a potential marker of early treatment resistance. Therapeutic strategies to address primary resistance to P are currently lacking. Little is known of the clinical efficacy of alternative dosing schedules of P, and its effect on TKa. Here we report serum TKa measured at different timepoints from samples collected within the MA38 (NCT02630693) study. Methods: MA38 is an open label randomised Phase 2 trial comparing two different schedules of P plus second-line ET in pts with ER-positive, HER2-negative MBC. Pts were assigned to receive physician’s choice ET plus either standard P dosing (125mg daily for 21 days on a 28-day cycle), or 100mg daily continuously. Serum samples were collected at baseline (BL; n=135), at 12 weeks (W12; n=122) and 24 weeks (W24; n=95). TKa was measured with DiviTum®, a refined ELISA-based assay (lower limit of detection [LLOD] = 100 DuA). Kaplan-Meier method estimated BL, W12 and W24 (95% CI) median PFS (mPFS; from randomization until progression by RECIST criteria or death) and overall survival (OS; from randomization until death from any cause) in groups of patients defined by dichotomizing TKa as “high” or “low” at the median. Results: MA38 enrolled 180 pts from December 2015 and February 2017 across Canada. Median follow up was 19 months. Overall, the median age was 60, and 90% of pts were post-menopausal. All pts had estrogen receptor-positive disease, and 64% had visceral metastases. On study, 56% received fulvestrant with P, 34% aromatase inhibitor and 10% tamoxifen. TKa was successfully measured in 100% of samples. Median TKa (mTKa) at BL was 234 DuA (IQR 138.5 - 438). BL TKa was not associated with clinical or pathological characteristics. TKa was prognostic at BL with mPFS of 5.5 months (mo) in pts with high TKa vs 16.3 mo with low TKa (HR=2.43; 95% CI, 1.6-3.7; p< 0.001). Similar results were obtained employing other previously reported cut off values. At multivariate analysis, BL TKa was independent from other prognostic factors including age, ECOG status and presence of visceral metastases (adjusted HR= 2.34; 95%CI 1.5- 3.6; p < 0.001). In terms of OS, BL TKa was an independent prognostic factor (adjusted HR=2.0; 95% CI, 1.1-3.7; p=0.02). At 12 mo, OS rate was 68% in pts with high BL TKa vs 92% in low TKa. Both for PFS and OS, no interaction between BL TKa and study arm was observed. At W12 mTKa was 129.5 DuA (IQR 100 - 219.8) and below LLOD (IQR 100 - 180) at W24. At these timepoints, landmark analyses showed no significant difference in PFS according to TKa. However, at W12 high TKa was significantly associated with worse OS (HR 2.0; 95%CI 1.0- 4.0; p=0.03), with a similar trend at W24 (HR 2.5; 95%CI 0.9-6.4; p=0.06). Conclusions: Baseline TKa is a reliable prognostic marker of both PFS and OS in pts treated with P and ET, further substantiating previous data. Monitoring TKa during treatment may provide important clinical information. A significant relationship between TKa and assigned treatment arm was not observed, suggesting TKa is not influenced by P treatment dose or intensity. These data confirm the role of baseline TKa as a new marker for patient stratification, and supports further investigation for the assessment of the clinical utility of TKa as a monitoring biomarker in the advanced setting. Citation Format: Amelia McCartney, Chiara Biagioni, Bingshu Chen, Lois Shepherd, Karen Gelmon, Anil A. Joy, Wendy Parulekar, Mattias Bergqvist, Ilenia Migliaccio, Angela Leo, Matteo Benelli, Emanuela Risi, Erica Moretti, Luca Livraghi, Laura Biganzoli, Luca Malorni. Serum thymidine kinase activity as a prognostic marker in women with metastatic breast cancer treated with two different schedules of palbociclib plus second-line endocrine therapy within the CCTG MA38 trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-02-27.
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- 2023
25. Novel Therapies for the Treatment of HER2-Positive Advanced Breast Cancer: A Canadian Perspective
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Cristiano Ferrario, Anna Christofides, Anil Abraham Joy, Kara Laing, Karen Gelmon, and Christine Brezden-Masley
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Canada ,Brain Neoplasms ,Receptor, ErbB-2 ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Breast Neoplasms ,Female ,Trastuzumab ,skin and connective tissue diseases ,Ado-Trastuzumab Emtansine - Abstract
The advent of anti-HER2 targeted therapies has dramatically improved the outcome of HER2-positive breast cancer; however, resistance to treatment in the metastatic setting remains a challenge, highlighting the need for novel therapies. The arrival of new treatment options and clinical trials examining the efficacy of novel agents may improve outcomes in the metastatic setting, including in patients with brain metastases. In the first-line setting, we can potentially cure a selected number of patients treated with pertuzumab + trastuzumab + taxane. In the second-line setting, clinical trials show that trastuzumab deruxtecan (T-DXd) is a highly effective option, resulting in a shift from trastuzumab emtansine (T-DM1) as the previous standard of care. Moreover, we now have data for patients with brain metastases to show that tucatinib + trastuzumab + capecitabine can improve survival in this higher-risk group and be an effective regimen for all patients in the third-line setting. Finally, we have a number of effective anti-HER2 therapies that can be used in subsequent lines of therapy to improve patient outcomes. This review paper discusses the current treatment options and presents a practical treatment sequencing algorithm in the context of the Canadian landscape.
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- 2022
26. Unwarranted imaging for distant metastases in patients with newly diagnosed ductal carcinoma in situ and stage I and II breast cancer
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Karen King, Brae Surgeoner, Derek Tilley, Anil Abraham Joy, and Sasha M. Lupichuk
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Adult ,Diagnostic Imaging ,0301 basic medicine ,medicine.medical_specialty ,Breast Neoplasms ,Unnecessary Procedures ,Bone and Bones ,Alberta ,Cohort Studies ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Medical imaging ,medicine ,Humans ,Registries ,Neoplasm Metastasis ,Stage (cooking) ,Aged ,Retrospective Studies ,Aged, 80 and over ,medicine.diagnostic_test ,business.industry ,Research ,Magnetic resonance imaging ,Guideline ,Middle Aged ,Ductal carcinoma ,medicine.disease ,Cancer registry ,Carcinoma, Intraductal, Noninfiltrating ,030104 developmental biology ,Positron emission tomography ,030220 oncology & carcinogenesis ,Practice Guidelines as Topic ,Female ,Surgery ,Radiology ,business - Abstract
In 2012, the American Society of Clinical Oncology (ASCO) released a Choosing Wisely Top Five list that included a recommendation against ordering advanced imaging tests to screen for metastases among asymptomatic patients with early breast cancer. Our provincial breast cancer staging guideline was subsequently updated. We report on the use of unwarranted bone scanning (BS), computed tomography (CT), nonbreast magnetic resonance imaging (MRI) and positron emission tomography (PET) among women diagnosed with stage 0–II breast cancer in Alberta in 2011–2015.The cohort was retrospectively ascertained from the Alberta Cancer Registry. We used additional provincial data sources to obtain information about diagnostic imaging tests completed from biopsy to surgical date plus 4 months. The reason for each BS, CT, MRI and PET was abstracted. We calculated the frequency of advanced imaging tests completed for routine metastatic screening.Of 10 142 patients included, 2887 (28.5%) had at least 1 advanced imaging test completed for routine metastatic screening. Of these 2887 patients, 438 (15.2%) had a follow-up BS, CT, MRI or PET, and 28 patients (1.0%) had a nonbreast imageguided biopsy. Use of routine advanced imaging tests did not change clearly over time.Our results demonstrate persistent use of advanced imaging tests for routine metastatic screening among patients with stage 0–II breast cancer despite the release of the ASCO Choosing Wisely recommendations and the update of our provincial breast cancer staging guideline. Investigation of strategies for guideline translation to improve upon value-based care of patients with early breast cancer is warranted.En 2012, l’American Society of Clinical Oncology (ASCO) a publié sa liste de 5 interventions à « Choisir avec soin », dans laquelle elle recommandait notamment de ne pas recourir aux techniques d’imagerie de pointe pour le dépistage des métastases chez les patientes atteintes d’un cancer du sein peu avancé et asymptomatique. Nos lignes directrices provinciales pour la stadification du cancer du sein ont été mises à jour en conséquence. Nous faisons aujourd’hui état de l’utilisation injustifiée de la scintigraphie osseuse (SO), de la tomodensitométrie (TDM), de l’imagerie par résonnance magnétique (IRM) non mammaire et de la tomographie par émission de positrons (TEP) chez les femmes ayant reçu un diagnostic de cancer du sein peu avancé (stade 0-II) en Alberta entre 2011 et 2015.La cohorte a été réunie de manière rétrospective à partir du registre albertain du cancer. Nous avons utilisé d’autres sources de données provinciales pour obtenir des renseignements sur les épreuves d’imagerie diagnostique effectuées entre les dates de la biopsie et les dates de la chirurgie plus 4 mois. Le motif invoqué pour recourir à chaque SO, TDM, IRM et TEP a été recueilli. Nous avons calculé la fréquence des épreuves d’imagerie de pointe effectuées pour un dépistage de routine des métastases.Sur les 10 142 patientes incluses, 2887 (28,5 %) avaient subi au moins 1 épreuve d’imagerie de pointe pour le dépistage de routine des métastases. Parmi ces 2887 patientes, 438 (15,2 %) ont subi une SO, une TDM, une IRM ou une TEP de suivi et 28 patientes (1,0 %) ont subi une biopsie non mammaire guidée par l’imagerie. L’utilisation de routine des épreuves d’imagerie de pointe n’a pas nettement changé avec le temps.Selon nos résultats, l’utilisation des épreuves d’imagerie de pointe pour le dépistage de routine des métastases persiste chez les patientes atteintes d’un cancer du sein de stade 0–II, malgré la publication des recommandations Choisir avec soin de l’ASCO et la mise à jour de nos lignes directrices provinciales concernant la stadification du cancer du sein. Il faudra se pencher sur des stratégies pour améliorer l’adoption de lignes directrices relatives aux soins véritablement utiles pour les patientes atteintes d’un cancer du sein peu avancé.
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- 2020
27. Progression-free Survival Outcome Is Independent of Objective Response in Patients With Estrogen Receptor-positive, Human Epidermal Growth Factor Receptor 2-negative Advanced Breast Cancer Treated With Palbociclib Plus Letrozole Compared With Letrozole: Analysis From PALOMA-2
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Eustratios Bananis, Miguel Martin, Richard S. Finn, Aurelio Castrellon, Anil Abraham Joy, Eric Gauthier, Hirofumi Mukai, Janice M. Walshe, Hope S. Rugo, A. Mori, D. Lu, Nadia Harbeck, Karen A. Gelmon, and Véronique Diéras
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Adult ,0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Pyridines ,Receptor, ErbB-2 ,Population ,Urology ,Breast Neoplasms ,Palbociclib ,Piperazines ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Medicine ,Breast ,Progression-free survival ,education ,Protein Kinase Inhibitors ,Mastectomy ,Response Evaluation Criteria in Solid Tumors ,Aged ,Aged, 80 and over ,education.field_of_study ,Aromatase Inhibitors ,business.industry ,Letrozole ,Hazard ratio ,Middle Aged ,medicine.disease ,Metastatic breast cancer ,Progression-Free Survival ,Intention to Treat Analysis ,030104 developmental biology ,Receptors, Estrogen ,Oncology ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Female ,business ,medicine.drug - Abstract
Background In PALOMA-2, palbociclib + letrozole significantly prolonged progression-free survival (PFS) versus placebo + letrozole in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2−) advanced breast cancer (ABC). We investigated clinical outcomes of patients who achieved or did not achieve a confirmed objective response (OR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (data cutoff: May 31, 2017). Patients and Methods Postmenopausal patients untreated for ER+/HER2− ABC were randomized 2:1 to palbociclib + letrozole or placebo + letrozole. Median PFS, median duration of OR, baseline characteristics, and palbociclib exposure were compared in patients with or without OR by treatment arm. Results In the intent-to-treat population, OR was achieved by 194 (44%) of 444 and 77 (35%) of 222 patients in the palbociclib and placebo arms, respectively (odds ratio, 1.5; 95% confidence interval [CI], 1.0-2.1; P = .0156). Regardless of treatment, more OR than non-OR patients had de novo metastatic disease (47%-50% and 28%-31%, respectively) and no prior endocrine therapy (55% and 35%-37%, respectively). Rates of palbociclib dose reduction owing to adverse events were similar regardless of OR (41% and 38%, respectively). Among the patients with OR during the study, approximately 50% achieved OR within the first 3 months regardless of treatment. The median PFS was significantly prolonged with palbociclib + letrozole versus placebo + letrozole in patients with measurable disease in both OR (37.2 months; 95% CI, 28.1 months to not estimable vs. 27.4 months; 95% CI, 22.2-31.1 months; hazard ratio, 0.66; 95% CI, 0.47-0.94; P = .009) and non-OR groups (10.9 months; 95% CI, 8.2-11.2 months vs. 5.6 months; 95% CI, 5.3-8.3 months; hazard ratio, 0.72; 95% CI, 0.54-0.97; P = .016). Conclusions Palbociclib + letrozole provided significant clinical benefit versus placebo + letrozole to patients with ER+/HER2− ABC regardless of achieving RECIST-defined OR. Pfizer; ClinicalTrials.gov : NCT01740427
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- 2020
28. Abstract P1-19-03: JAVELIN PARP Medley, a phase 1b/2 study of avelumab plus talazoparib: Results from advanced breast cancer cohorts
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Gabor Rubovszky, Aditya Bardia, J. Thaddeus Beck, Ross A. Stewart, Mateusz Opyrchal, Melinda L. Telli, Mustafa Khasraw, Smita S. Saraykar, David R. Wise, Mikhail Dvorkin, Anita Scheuber, Rossano Cesari, Panagiotis A. Konstantinopoulos, Anil A. Joy, Timothy A. Yap, Jame Abraham, Colombe Chappey, Matthew D. Galsky, and Daria Stypinski
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0301 basic medicine ,Oncology ,Cancer Research ,education.field_of_study ,medicine.medical_specialty ,business.industry ,Population ,Cancer ,Neutropenia ,medicine.disease ,03 medical and health sciences ,Regimen ,030104 developmental biology ,0302 clinical medicine ,Breast cancer ,030220 oncology & carcinogenesis ,Internal medicine ,Cohort ,PARP inhibitor ,Medicine ,business ,education ,Progressive disease - Abstract
Background: Avelumab, a human IgG1 anti–PD-L1 monoclonal antibody, has shown antitumor activity and a manageable safety profile in several tumor types. Talazoparib, an orally available PARP inhibitor, is approved for the treatment of patients with deleterious or suspected deleterious germline BRCA1/2-mutated HER2− locally advanced (LA) or metastatic (M) breast cancer (BC). Preclinical data suggest that PARP inhibitors may have synergistic activity when administered in combination with immune checkpoint inhibitors. We report results from patients with LA/MBC enrolled in the phase 1b/2, multicohort JAVELIN PARP Medley study (NCT03330405). Methods: In phase 1b (cohort 1), patients with advanced solid tumors who had received ≥1 prior standard of care chemotherapy (CT) regimen were treated with avelumab 800 mg IV every 2 weeks (Q2W) in combination with talazoparib 1.0 mg orally once daily (QD) (dose de-escalation to 0.75 or 0.5 mg permitted following toxicity). In 2 phase 2 cohorts, eligible patients had either LA/M triple-negative BC (TNBC, cohort 2A) or LA/M hormone receptor positive (HR+), HER2−, DNA damage repair defect-positive BC (cohort 2B). Patients in cohort 2A had received 0 to 2 prior CT regimens (no progression on prior platinum-based CT) and patients in cohort 2B had received prior standard of care hormone therapy in either the adjuvant and/or LA/M setting followed by 0 to 2 prior CT regimens (no progression on prior platinum-based CT). The primary endpoint for phase 1b was first-cycle dose-limiting toxicities (DLTs) and for phase 2 was objective response (investigator assessed per RECIST v1.1). Adverse events (AEs) were characterized using National Cancer Institute Common Terminology Criteria for AEs v4.03. Results: By the data cutoff on December 24, 2018, 34 patients had been treated in cohorts 1 and 2. Twelve patients with advanced solid tumors were treated in cohort 1 (including 2 patients with TNBC); 3 patients (25.0%) had a first-cycle DLT: grade 3 neutropenia, (n=1) and grade 3 thrombocytopenia, (n=2). Best overall response (BOR) was partial response (PR) in 1 patient, stable disease (SD) in 3, progressive disease (PD) in 6, and non-complete response/non-PD in 1 patient with metastatic castration-resistant prostate cancer and non-measurable disease at baseline; 1 patient was not evaluable for response. Both patients with TNBC had a BOR of SD and remained on treatment for ≥9 months. Objective response rate in this pre-treated and heterogenous population was 8.3% (95% CI, 0.2, 38.5). Based on the phase 1b data, the recommended phase 2 dose was avelumab 800 mg Q2W and talazoparib 1 mg QD. By data cutoff, 22 patients had been treated in cohorts 2A (n=19) and 2B (n=3); median age was 56 and 50 years, respectively. In cohort 2A, 12 patients were evaluable for disease assessment; BOR was PR in 1, SD in 6, and PD in 5. All 3 patients in cohort 2B were non-evaluable for response at data cutoff. Treatment-related AEs (TRAEs) of any grade occurred in 11 patients (91.7%) in cohort 1, and 18 (94.7%) patients in cohort 2A. In cohort 2A, the most common TRAEs were anemia (57.9%), nausea (26.3%), fatigue (21.1%) and thrombocytopenia (21.1%); 9 patients (47.4%) had grade ≥3 TRAEs. There were no treatment-related deaths. Safety data from cohort 2B are not reported owing to low patient numbers. Observed pharmacokinetic (PK) data for avelumab 800 mg Q2W were similar to simulated data derived from a population PK model developed using 10 mg/kg dosing. Conclusions: Avelumab 800 mg Q2W administered in combination with talazoparib 1 mg QD in patients with advanced solid tumors, showed preliminary antitumor activity and a manageable safety profile, which was comparable to the safety profiles of the single agents. The study is ongoing; updated safety and efficacy data, and biomarker data will be presented. Citation Format: Timothy A Yap, Panagiotis Konstantinopoulos, Melinda L. Telli, Smita Saraykar, J Thaddeus Beck, Matthew D. Galsky, Jame Abraham, David R. Wise, Mustafa Khasraw, Gabor Rubovszky, Mikhail Dvorkin, Anil A Joy, Mateusz Opyrchal, Daria Stypinski, Colombe Chappey, Ross Stewart, Rossano Cesari, Anita Scheuber, Aditya Bardia. JAVELIN PARP Medley, a phase 1b/2 study of avelumab plus talazoparib: Results from advanced breast cancer cohorts [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-19-03.
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- 2020
29. Avelumab Plus Talazoparib in Patients With Advanced Solid Tumors
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Timothy A, Yap, Aditya, Bardia, Michael, Dvorkin, Matthew D, Galsky, J Thaddeus, Beck, David R, Wise, Oleg, Karyakin, Gábor, Rubovszky, Nikolay, Kislov, Kristoffer, Rohrberg, Anil Abraham, Joy, Melinda L, Telli, Alison M, Schram, Umberto, Conte, Colombe, Chappey, Ross, Stewart, Daria, Stypinski, Elisabete, Michelon, Rossano, Cesari, and Panagiotis A, Konstantinopoulos
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Cancer Research ,Oncology - Abstract
ImportancePreclinical data suggest that poly(ADP-ribose) polymerase (PARP) inhibitors have synergistic activity when combined with immune checkpoint inhibitors (ICIs); however, it is unknown which tumor types or molecular subtypes may benefit from this combination.ObjectiveTo investigate responses associated with the combination of avelumab and talazoparib in different tumor types and/or molecular subtypes.Design, Setting, and ParticipantsIn this phase 1b and 2 basket nonrandomized controlled trial, patients with advanced solid tumors were enrolled in the following cohorts: non–small cell lung cancer (NSCLC); DNA damage response (DDR)–positive NSCLC; triple-negative breast cancer (TNBC); hormone receptor–positive, human epidermal growth factor receptor 2 (ERBB2)–negative, DDR-positive breast cancer; recurrent, platinum-sensitive ovarian cancer (OC); recurrent, platinum-sensitive, BRCA1/2-altered OC; urothelial cancer; metastatic castration-resistant prostate cancer (mCRPC); DDR-positive mCRPC; and BRCA1/2- or ATM-altered solid tumors. Data were analyzed between June 17, 2021, and August 6, 2021.InterventionsAll patients in phases 1b and 2 received avelumab plus talazoparib.Main Outcomes and MeasuresThe phase 1b primary end point was dose-limiting toxic effects. The phase 2 primary end point was objective response, measured as objective response rate (ORR). Secondary end points included safety, time to response, duration of response (DOR), progression-free survival, time to prostate-specific antigen progression and PSA response of 50% or greater (for mCRPC), cancer antigen 125 response (for OC), pharmacokinetics, immunogenicity, and biomarkers.ResultsA total of 223 patients (mean [SD] age, 63.2 [11.0] years; 117 [52.5%] men) were treated, including 12 patients in phase 1b and 211 patients in phase 2. The recommended phase 2 dose was avelumab 800 mg every 2 weeks plus talazoparib 1 mg once daily. In phase 2, the ORR was 18.2% (95% CI, 5.2%-40.3%) in patients with TNBC; 34.8% (95% CI, 16.4%-57.3%) in patients with HR-positive, ERBB2-negative, and DDR-positive BC; and 63.6% (95% CI, 30.8%-89.1%) in patients with platinum-sensitive, BRCA1/2-altered OC. Responses occurred more frequently in patients with BRCA1/2-altered tumors. Durable responses were observed in patients with TNBC (median [range] DOR, 11.1 [3.4-20.4] months); HR-positive, ERBB2-negative, and DDR-positive BC (median [range] DOR, 15.7 [3.9 to ≥20.6] months); and BRCA1/2-altered OC (median DOR not reached; range, 5.6 to ≥18.4 months). The most common grade 3 or greater treatment-related adverse events were anemia (75 patients [33.6%]), thrombocytopenia (48 patients [21.5%]), and neutropenia (31 patients [13.9%]).Conclusions and RelevanceThis nonrandomized controlled trial found that ORRs for avelumab plus talazoparib were comparable with those with PARP inhibitor or ICI monotherapy. Prolonged DOR in patients with TNBC; HR-positive, ERBB2-negative, and DDR-positive BC; and BRCA1/2-altered OC warrant further investigation in randomized clinical trials. These data highlight the importance of prospective patient selection in future studies of ICI and PARP-inhibitor combinations.Trial RegistrationClinicalTrials.gov Identifier: NCT03330405
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- 2023
30. Genome profiles of pathologist-defined cell clusters by multiregional LCM and G&T-seq in one triple-negative breast cancer patient
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Sveta Silverman, Weiwei Wang, Deanna L. Hockley, Lynne M. Postovit, John R. Mackey, Xi Zhang, Zhongyi Zhu, Bo Li, Guibo Li, Qing Zhou, Yong Hou, Chao Chen, Tracy Jordan, Gane Ka-Shu Wong, Si Qiu, Xiuqing Zhang, Anil A. Joy, and Feng Lin
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Ribosomal Proteins ,Pathology ,medicine.medical_specialty ,Medicine (General) ,Axillary lymph nodes ,lymphovascular invasion ,Triple Negative Breast Neoplasms ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Article ,Metastasis ,Young Adult ,Breast cancer ,R5-920 ,Fatal Outcome ,medicine ,metastasis ,Humans ,Cell Lineage ,Lymphocytes ,RNA, Neoplasm ,Triple-negative breast cancer ,Phylogeny ,Laser capture microdissection ,Cell Aggregation ,Lymphatic Vessels ,G&T-seq ,Genome, Human ,Cancer ,High-Throughput Nucleotide Sequencing ,LCM ,Epithelial Cells ,DNA, Neoplasm ,medicine.disease ,Prognosis ,Primary tumor ,Clone Cells ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,Lymphatic system ,Lymphatic Metastasis ,triple-negative breast cancer ,Disease Progression ,Female ,Lymph Nodes - Abstract
Summary Pathological examination is the gold standard for cancer diagnosis, and breast tumor cells are often found in clusters. We report a case study on one triple-negative breast cancer (TNBC) patient, analyzing tumor development, metastasis, and prognosis with simultaneous DNA and RNA sequencing of pathologist-defined cell clusters from multiregional frozen sections. The cell clusters are isolated by laser capture microdissection (LCM) from primary tumor tissue, lymphatic vessels, and axillary lymph nodes. Data are reported for a total of 97 cell clusters. A combination of tumor cell-cluster clonality and phylogeny reveals 3 evolutionarily distinct pathways for this patient, each associated with a unique mRNA signature, and each correlated with disparate survival outcomes. Hub gene analysis indicates that extensive downregulation of ribosomal protein mRNA is a potential marker of poor prognosis in breast cancer., Graphical abstract, Highlights Pathologically diverse cell clusters share genomic and transcriptomic profiles Transcriptome-defined clones are more complex than genome-defined clones Three distinct pathways were inferred, each with disparate survival outcomes Lower expression of ribosomal proteins may be an indicator of poor prognosis, Zhu et al. reveal the complexity of tumor development, metastasis, and prognosis by simultaneous DNA and RNA sequencing of pathologist-defined cell clusters, excised through laser capture microdissection from multiregional frozen sections of a triple-negative breast cancer patient.
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- 2021
31. A Canadian national guideline on the neoadjuvant treatment of invasive breast cancer, including patient assessment, systemic therapy, and local management principles
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Sonal, Gandhi, Muriel, Brackstone, Nicole J Look, Hong, Debjani, Grenier, Elysia, Donovan, Fang-I, Lu, Mia, Skarpathiotakis, Justin, Lee, Jean-Francois, Boileau, Francisco, Perera, Christine, Simmons, Anil A, Joy, William T, Tran, and Shelyna, Khalfan
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Cancer Research ,Canada ,Consensus ,Oncology ,Adjuvants, Immunologic ,Humans ,Breast Neoplasms ,Female ,Neoadjuvant Therapy - Abstract
Purpose The neoadjuvant treatment of breast cancer (NABC) is a rapidly changing area that benefits from guidelines integrating evidence with expert consensus to help direct practice. This can optimize patient outcomes by ensuring the appropriate use of evolving neoadjuvant principles. Methods An expert panel formulated evidence-based practice recommendations spanning the entire neoadjuvant breast cancer treatment journey. These were sent for practice-based consensus across Canada using the modified Delphi methodology, through a secure online survey. Final recommendations were graded using the GRADE criteria for guidelines. The evidence was reviewed over the course of guideline development to ensure recommendations remained aligned with current relevant data. Results Response rate to the online survey was almost 30%; representation was achieved from various medical specialties from both community and academic centres in various Canadian provinces. Two rounds of consensus were required to achieve 80% or higher consensus on 59 final statements. Five additional statements were added to reflect updated evidence but not sent for consensus. Conclusions Key highlights of this comprehensive Canadian guideline on NABC include the use of neoadjuvant therapy for early stage triple negative and HER2 positive breast cancer, with subsequent adjuvant treatments for patients with residual disease. The use of molecular signatures, other targeted adjuvant therapies, and optimal response-based local regional management remain actively evolving areas. Many statements had evolving or limited data but still achieved high consensus, demonstrating the utility of such a guideline in helping to unify practice while further evidence evolves in this important area of breast cancer management.
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- 2021
32. Current and future landscape of targeted therapy in HER2-positive advanced breast cancer: redrawing the lines
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Christine Simmons, Daniel Rayson, Anil Abraham Joy, Jan-Willem Henning, Julie Lemieux, Heather McArthur, Paul B. Card, Rebecca Dent, and Christine Brezden-Masley
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T-DM1 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,tucatinib ,HER2-positive ,T-DXd ,neratinib ,trastuzumab ,breast cancer ,Oncology ,pertuzumab ,advanced disease ,Systematic Review ,skin and connective tissue diseases ,RC254-282 - Abstract
Background: Evidence to date supports continued human epidermal growth factor receptor 2 (HER2) suppression beyond progression on HER2-directed therapy for advanced HER2-positive breast cancer. Data from several phase II and III trials evaluating HER2-directed therapy following second-line T-DM1 have recently become available. Methods: We performed a systematic search of the published and presented literature to identify phase II and phase III trials assessing novel HER2-targeted agents as third-line therapy or beyond for HER2-positive advanced breast cancer using search terms ‘breast cancer’ AND ‘HER2’ AND ‘advanced’ AND (‘phase II’ OR ‘phase III’). Results: Eight clinical trials reporting efficacy outcomes on third-line or greater HER2-directed therapy for HER2-positive advanced breast cancer were identified. In phase III trials, margetuximab and neratinib combinations demonstrated significant 1.3-month (hazard ratio, HR = 0.71, p Conclusion: Tucatinib plus trastuzumab and capecitabine significantly prolongs OS, and promising preliminary response outcomes for trastuzumab-deruxtecan suggest that sequencing of these regimens following second-line therapy is reasonable.
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- 2021
33. Advanced Cancer as a Chronic Disease: Introduction
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Edith Pituskin, Anil A. Joy, and Alysa Fairchild
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medicine.medical_specialty ,Chronic disease ,Text mining ,Oncology (nursing) ,business.industry ,Neoplasms ,Chronic Disease ,MEDLINE ,Medicine ,Humans ,business ,Intensive care medicine ,Advanced cancer - Published
- 2021
34. Two-year results of a randomised trial comparing 4- versus 12-weekly bone-targeted agent use in patients with bone metastases from breast or castration-resistant prostate cancer
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Christopher M. Booth, Mashari Alzahrani, Lisa Vandermeer, Michelle Liu, Anil A. Joy, Michael Ong, Megan Tu, Mark Clemons, Carol Stober, REaCT investigators, Gregory R. Pond, Mihaela Mates, Olexiy Aseyev, Phillip S. Blanchette, Scott Ernst, Dean Fergusson, and Kednapa Thavorn
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Oncology ,medicine.medical_specialty ,Prostate cancer ,business.industry ,Hazard ratio ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Bisphosphonates ,Diseases of the musculoskeletal system ,medicine.disease ,Breast cancer ,Denosumab ,RC925-935 ,Internal medicine ,Toxicity ,Post-hoc analysis ,medicine ,Cumulative incidence ,Dosing ,business ,RC254-282 ,medicine.drug - Abstract
Background We present the 2-year results of a randomised trial comparing 4- versus 12-weekly bone-targeting agents (BTAs) in patients with bone metastases from breast or castration-resistant prostate cancer (CRPC). Patients and Methods Patients with bone metastases from breast or CRPC, who were going to start or were already receiving BTAs, were randomised to 4- or 12-weekly BTA treatment for 2 years. The endpoints were: symptomatic skeletal events (SSE) rates, time to SSEs, toxicity and cost-effectiveness. Results Of 263 patients (160 breast cancer, 103 CRPC), 133 (50.6%) and 130 (49.4%) were randomised to the 4- and 12-weekly groups, respectively. BTAs included denosumab (56.3%), zoledronate (24.0%) and pamidronate (19.8%). After 2 years, the cumulative incidence rate (95% CI) of SSEs was 32.7% (24.6% to 41.1%) and 28.1% (20.3% to 36.4%) for the 4- and 12-weekly intervention groups respectively. The hazard ratio for time to first SSE was 0.96 (95% CI = 0.63 to 1.47). However, in a post hoc analysis, those patients who had an on-study SSE, there was a small non-statistical increased risk of subsequent SSEs among patients on the 12-weekly dosing arm (HR = 1.14; 95% CI – 0.90–1.44). BTA-related toxicity rates were similar between study arms. A cost-utility analysis showed that 12-weekly BTA is cost-effective from a public payer’s perspective. Conclusion These results in addition to those previously reported for de-escalating zoledronate, would support that de-escalation of commonly used BTAs is a reasonable and economically valid treatment option. While not statistically significant, the increase in subsequent SSEs in the 12-weekly arm requires further exploration.
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- 2021
35. Rapid atrophy of cardiac left ventricular mass in patients with non‐small cell carcinoma of the lung
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Charles Butts, Randeep Sangha, Naveen S. Basappa, Andrea Gallivan, Peter A. Kavsak, Quincy Chu, Vickie E. Baracos, Seyyed Mohammad Reza Kazemi-Bajestani, Michael Smylie, Harald Becher, and Anil Abraham Joy
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0301 basic medicine ,Male ,lcsh:Diseases of the musculoskeletal system ,Cachexia ,Lung Neoplasms ,Left ventricular mass ,Electrocardiography ,Ventricular Dysfunction, Left ,0302 clinical medicine ,Weight loss ,Carcinoma, Non-Small-Cell Lung ,Orthopedics and Sports Medicine ,Cancer ,education.field_of_study ,Ejection fraction ,Cardiac atrophy ,lcsh:Human anatomy ,Organ Size ,Middle Aged ,Prognosis ,3. Good health ,Muscular Atrophy ,Echocardiography ,030220 oncology & carcinogenesis ,Cardiology ,Original Article ,Female ,medicine.symptom ,Cardiac function curve ,medicine.medical_specialty ,Heart Ventricles ,Population ,lcsh:QM1-695 ,03 medical and health sciences ,Atrophy ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,education ,Aged ,Performance status ,business.industry ,Odds ratio ,Original Articles ,medicine.disease ,030104 developmental biology ,lcsh:RC925-935 ,business ,Biomarkers - Abstract
Background Cancer is a systemic catabolic condition affecting skeletal muscle and fat. We aimed to determine whether cardiac atrophy occurs in this condition and assess its association with cardiac function, symptoms, and clinical outcomes. Methods Treatment naïve metastatic non‐small cell lung cancer patients (n = 50) were assessed prior to and 4 months after commencement of carboplatin‐based palliative chemotherapy. Methods included echocardiography for left ventricular mass (LVM) and LV function [LV ejection fraction, global longitudinal strain (GLS), diastolic function], computed tomography to quantify skeletal muscle and total adipose tissue, Eastern Cooperative Oncology Group Performance Status (ECOG‐PS), validated questionnaires for dyspnoea and fatigue, plasma biomarkers, tumour response to therapy, and overall survival. Results During 112 ± 6 days, the median change in LVM was −8.9% [95% confidence interval (95% CI) −10.8 to −4.8, P < 0.001]. Quartiles of LVM loss were −20.1%, −12.9%, −4.8%, and +5.5%. Losses of muscle, adipose tissue, and LVM were frequently concurrent; LVM loss > median value was associated with loss of skeletal muscle [odds ratio (OR) = 4.5, 95% CI: 1.4–14.8, P=0.01] and loss of total adipose tissue (OR = 10.0, 95% CI: 2.7–36.7, P < 0.001). LVM loss was associated with decreased GLS (OR = 6.6, 95% CI: 1.9–22.7, P=0.003) but not with LV ejection fraction or diastolic function. In the population overall, plasma levels of C‐reactive protein (P=0.008), high sensitivity troponin T (hs‐TnT) (P=0.03), and galectin‐3 (P=0.02) increased over time, while N‐terminal pro B‐type natriuretic peptide and hs‐cTnI did not change over time. C‐reactive protein was the only biomarker associated with LVM loss but at the univariate level only. Independent predictors of LVM loss were prior weight loss (adjusted OR = 10.2, 95% CI: 2.2–46.9, P=0.003) and tumour progression (adjusted OR = 14.6, 95% CI: 1.4–153.9, P=0.02). LVM loss was associated with exacerbations of fatigue (OR = 6.6, 95% CI: 1.9–22.7, P=0.003), dyspnoea (OR = 9.3, 95% CI: 2.4–35.8, P
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- 2019
36. Fine‐mapping of a novel premenopausal breast cancer susceptibility locus at Chr4q31.22 in Caucasian women and validation in African and Chinese women
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Carol E. Cass, Sunita Ghosh, Sambasivarao Damaraju, Mahalakshmi Kumaran, John R. Mackey, Wei Zheng, Yutaka Yasui, and Anil Abraham Joy
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Adult ,Cancer Research ,Black People ,Datasets as Topic ,Breast Neoplasms ,Locus (genetics) ,Genome-wide association study ,Biology ,Polymorphism, Single Nucleotide ,White People ,genome‐wide association studies ,Alberta ,Young Adult ,fine‐mapping ,03 medical and health sciences ,Age Distribution ,breast cancer ,0302 clinical medicine ,Breast cancer ,Asian People ,medicine ,Humans ,SNP ,Genetic Predisposition to Disease ,Promoter Regions, Genetic ,Enhancer ,Gene ,Aged ,menopausal status ,Aged, 80 and over ,Genetics ,Chromosome Mapping ,Odds ratio ,Middle Aged ,medicine.disease ,Postmenopause ,Minor allele frequency ,Enhancer Elements, Genetic ,Premenopause ,Oncology ,Genetic Loci ,Case-Control Studies ,030220 oncology & carcinogenesis ,Female ,susceptibility variants ,Chromosomes, Human, Pair 4 ,Cancer Epidemiology - Abstract
We previously identified a novel breast cancer susceptibility variant on chromosome 4q31.22 locus (rs1429142) conferring risk among women of European ancestry. Here, we report replication of findings, validation of the variant in diverse populations and fine‐mapping of the associated locus in Caucasian population. The SNP rs1429142 (C/T, minor allele frequency 18%) showed association for the overall breast cancer risk in Stages 1–4 (n = 4,331 cases/4271 controls; p = 4.35 × 10−8; odds ratio, ORC‐allele,1.25), and an elevated risk among premenopausal women (n = 1,503 cases/4271 controls; p = 5.81 × 10−10; ORC‐allele 1.40) in European populations. SNP rs1429142 was associated with premenopausal breast cancer risk in women of African (T/C; p‐value 1.45 × 10−02; ORC‐allele 1.2) but not from Chinese ancestry. Fine‐mapping of the locus revealed several potential causal variants which are present within a single association signal, revealed from the conditional regression analysis. Functional annotation of the potential causal variants revealed three putative SNPs rs1366691, rs1429139 and rs7667633 with active enhancer functions inferred based on histone marks, DNase hypersensitive sites in breast cell line data. These putative variants were bound by transcription factors (C‐FOS, STAT1/3 and POL2/3) with known roles in inflammatory pathways. Furthermore, Hi‐C data revealed several short‐range interactions in the fine‐mapped locus harboring the putative variants. The fine mapped locus was predicted to be within a single topologically associated domain, potentially facilitating enhancer–promoter interactions possibly leading to the regulation of nearby genes., What's new? To date, genome‐wide association studies have addressed familial or postmenopausal breast cancer susceptibility variants. However, genetic predisposition for sporadic premenopausal breast cancer risk is unknown. This study reports a novel variant (at 4q31.22) associated with elevated risk for premenopausal breast cancer among women from European and African ancestry. The fine‐mapped locus was predicted to be within a single topologically associated domain, potentially facilitating enhancer‐promoter interactions leading to the regulation of nearby genes.
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- 2019
37. Creating a pragmatic trials program for breast cancer patients: Rethinking Clinical Trials (REaCT)
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Kednapa Thavorn, Anil Abraham Joy, Mark Clemons, Carol Stober, Arif Awan, Bassam Basulaiman, Angel Arnaout, Brian Hutton, Nadia Califaretti, John Hilton, Dean Fergusson, Andrew Robinson, Marta Sienkiewicz, and Lisa Vandermeer
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0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Accrual ,business.industry ,Patient-centered outcomes ,Psychological intervention ,medicine.disease ,3. Good health ,law.invention ,Clinical trial ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Breast cancer ,Systematic review ,Oncology ,Randomized controlled trial ,law ,030220 oncology & carcinogenesis ,Family medicine ,Medicine ,business ,Healthcare providers - Abstract
The proportion of breast cancer patients enrolled in clinical trials is falling. The Rethinking Clinical Trials (REaCT) program was developed to challenge some of the contemporary barriers responsible for this fall in accrual. In this article, we review the successes and challenges our program has faced. The REaCT program was created to improve care and outcomes for cancer patients through surveys of patients and healthcare providers, systematic reviews, economic evaluations, and the performance of pragmatic randomized trials with patient-centered outcomes. Likely, the greatest difference to conventional trial methodologies has been our widespread use of the integrated consent model (ICM) incorporating oral consent. Between 2014 and 2018, the program has recruited over 2000 patients to 15 randomized studies at 11 Canadian cancer centers. The REaCT program has completed and published five patient surveys, six healthcare provider surveys, ten systematic reviews, performed four economic evaluations, opened 15 clinical trials comparing standard of care interventions (two surgical, two adjuvant chemotherapy, five adjuvant supportive care, one radiology, two vascular devices, two palliative supportive care, and one molecular diagnostics). Patient surveys have shown high levels of satisfaction with the ICM. The REaCT program was developed to tackle important practice questions that will better guide optimal practice and to increase the availability of pragmatic clinical trials. While many challenges remain, future strategies will involve including more study sites and efforts to integrate novel information technology strategies.
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- 2019
38. Abstract P4-13-06: Real-world experience using exemestane and everolimus in patients with hormone receptor positive/HER2 negative breast cancer with and without prior CDK4/6 inhibitor exposure
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SM Lupichuk, B Recaldin, Anil A. Joy, NA Nixon, and A Mututino
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Oncology ,Cancer Research ,medicine.medical_specialty ,Everolimus ,Aromatase inhibitor ,business.industry ,medicine.drug_class ,Cancer ,medicine.disease ,Metastatic breast cancer ,chemistry.chemical_compound ,Breast cancer ,Exemestane ,chemistry ,Hormone receptor ,Internal medicine ,medicine ,Hormonal therapy ,business ,medicine.drug - Abstract
Background: For patients with metastatic hormone receptor (HR)-positive, HER2-negative breast cancer who progress on a non-steroidal aromatase inhibitor (NSAI), exemestane plus everolimus (EE) has been shown to prolong progression-free survival in comparison to exemestane alone. In the current era, many patients are now receiving a CDK4/6 inhibitor with first-line NSAI therapy. There is limited data describing the utilization and effectiveness of treatments following hormonal therapy - CDK4/6 inhibitor combinations, including EE. The aim of this study was to describe the real-world clinical experience and outcomes associated with EE amongst patients with and without prior CDK4/6 inhibitor exposure treated in our provincial jurisdiction. Methods: All patients prescribed EE from January 1, 2016 through May 10, 2018 were obtained from the Alberta Health Services CancerControl Breast Data Mart (BDM). Patients with HER2+ disease, had received Results: There were 110 patients extracted and 88 eligible for analysis (3 excluded for HER2+ disease, 14 for receipt of Conclusion: In a cohort of patients who have progressed on hormonal therapy + CDK4/6 inhibitor within 2 years, subsequent EE is a clinically meaningful treatment option in the setting of HR-positive/HER2-negative metastatic breast cancer. TOT was similar for CDK4/6 inhibitor exposed and naïve patients. Citation Format: Lupichuk SM, Recaldin B, Nixon NA, Mututino A, Joy AA. Real-world experience using exemestane and everolimus in patients with hormone receptor positive/HER2 negative breast cancer with and without prior CDK4/6 inhibitor exposure [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-13-06.
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- 2019
39. Abstract PD1-10: Randomized phase II study comparing two different schedules of palbociclib plus second line endocrine therapy in women with estrogen receptor positive, HER2 negative advanced/metastatic breast cancer: CCTG MA38 (NCT02630693)
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Anil A. Joy, S Taylor, M. Mates, David W. Cescon, Y Rahim, Louise Bordeleau, Mark Clemons, Bingshu E. Chen, Karen A. Gelmon, Julie Lemieux, Wendy R. Parulekar, J-P Ayoub, John D. Bartlett, Christine Desbiens, C Winch, and Timothy J. Whelan
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,education.field_of_study ,business.industry ,Population ,Phases of clinical research ,Palbociclib ,Neutropenia ,medicine.disease ,Metastatic breast cancer ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Breast cancer ,Tolerability ,030220 oncology & carcinogenesis ,Internal medicine ,Medicine ,business ,education ,Febrile neutropenia - Abstract
Background: Palbociclib is approved for treatment of ER+, HER2- ABC at a standard dose of 125 mg po daily 3 weeks on/1 week off (STD). We evaluated the efficacy, safety, quality of life (QOL) and compliance of a 100 mg continuous daily dose (CDD) of palbociclib based on modeling data that suggested efficacy and tolerability. Methods: Canadian Cancer Trials Group (CCTG) led a randomized phase II trial (CCTG MA38) to estimate the efficacy of palbociclib 100 mg po on CDD schedule (Arm 1) relative to 125 mg po STD schedule (Arm 2) with physician choice endocrine therapy. Eligible patients had ER+, HER2- ABC, post progression on first line metastatic endocrine therapy or progressed while on/within 12 months of completion of adjuvant endocrine therapy. One line of palliative chemotherapy in ABC was allowed. Stratification factors were: visceral metastases, duration of prior endocrine therapy and planned endocrine therapy. Primary Outcome measure was investigator reported PFS; secondary outcome measures included: RR, OS, safety (CTCAE V4.0), and QOL (EORTC QLQ-C30). The sample size was 180 to enable estimation of the HR between arms with the upper bound of the 90% CI 1.36 times the estimated HR and the lower bound is 0.74 times the estimated HR. Results: 180 patients were enrolled across Canada from Dec 2015 to Feb 2017. The database was locked April 16 2018 after prespecified PFS events reached at a median follow-up of 19 months for all patients. For the whole population: median age was 60.5 years (21% ≥ 70 years); ECOG 0/1 95%; postmenopausal 91%; visceral metastases 67%. Planned endocrine therapy: aromatase inhibitor 33%, fulvestrant 57%, tamoxifen 10%. Efficacy analyses CDD vs STD: PFS stratified univariate HR 0.93 (90% CI 0.66-1.30); multivariate Cox model analysis (covariates ECOG PS, age, histology, grade): HR 0.92 (90% CI 0.67-1.25). Median PFS CDD: 9.33 months (90% CI 6.93-13.90) and STD: 11.30 months (90% CI 8.08- 13.83) Secondary analyses CDD vs STD: OS stratified univariate HR: 1.07 (90% CI 0.67-1.69); multivariate HR 1.14 (90%CI 0.75-1.75); median OS for CDD: 20.73 months (90% CI 19.29-23.30) and 21.39 months (90% CI 19.65 to 26.68) for STD. RR and median duration of response: 11.1% vs 12.4% (p=0.84) and 126 vs 169 days (p=0.86), respectively. Palbociclib drug exposure CDD vs STD: median daily dose (mg) 87 vs 125; median dose intensity (mg/week) 571.2 vs 613.5; ≥ 90% planned dose intensity, 41% vs 54%. Dose modification (withhold and/or reduction) rate CDD vs STD for neutropenia was 70% vs 40%. Grade 3/4 neutropenia 69% vs 53%; febrile neutropenia 3% each arm. Non-hematological toxicity profiles were comparable for both arms. No significant differences were seen in QOL domains. Conclusion: Palbociclib is active and tolerable when administered on either a 100 mg CDD or a 125 mg STD schedule. CDD schedule had higher rates of grade 3/4 neutropenia and dose modifications. Post approval evaluation of alternate dosing schedules for targeted therapies provides useful information regarding drug activity, toxicity and adherence. Citation Format: Parulekar WR, Joy AA, Gelmon K, Mates M, Desbiens C, Clemons M, Taylor S, Lemieux J, Bartlett J, Whelan T, Ayoub J-P, Cescon D, Bordeleau L, Rahim Y, Winch C, Chen BE. Randomized phase II study comparing two different schedules of palbociclib plus second line endocrine therapy in women with estrogen receptor positive, HER2 negative advanced/metastatic breast cancer: CCTG MA38 (NCT02630693) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD1-10.
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- 2019
40. Heal-me PiONEer (personalized online nutrition and exercise): An RCT assessing 2 levels of app-based programming in individuals with chronic disease
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Puneeta, Tandon, Graeme, Purdy, Kathleen P, Ismond, Christofer, Cruz, Evelyn, Etruw, Kirsten, Suderman, Ashley, Hyde, Michael, Stickland, John C, Spence, Dale C, Lien, Rahima, Bhanji, Carla M, Prado, Antonio Miguel, Cruz, Anil A, Joy, Maryna, Yaskina, Jeff, Round, Kate, Harback, Raj, Padwal, and Margaret L, McNeely
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Adult ,Chronic Disease ,Quality of Life ,Humans ,Pharmacology (medical) ,General Medicine ,Exercise ,Mobile Applications ,Exercise Therapy - Abstract
Background App-based strategies are a promising solution to deliver nutrition and exercise interventions during social distancing. With limited RCT data in individuals with chronic disease, further information is required both to determine impact, and to guide delivery. The Heal-Me app is an evidence-based, theoretically informed nutrition and exercise solution that can be tailored for use across a range of individuals with chronic disease. As compared to controls receiving educational material, the aim of this study is to assess the acceptability, effectiveness, and cost of Heal-Me app programming delivered alongside two levels of dietitian and exercise-specialist support. Methods Heal-Me PiONEer is a 12-week, 3-arm RCT with randomization to one of three study groups (n=72 per group, 216 total). Group 1 (control: educational material), Group 2 (Heal-Me app + virtual group dietitian/exercise-specialist sessions), Group 3 (Heal-Me app + virtual group and 1-to-1 dietitian/exercise-specialist sessions). Inclusion criteria: adults with cancer, chronic lung disease or status post-transplantation from liver or lung transplant; previous completion of an exercise rehabilitation program; access to an internet-connected device. Study outcomes measured at study weeks 0 and 12 include: Primary - Lower Extremity Functional Scale; Secondary - virtual physical function tests, loneliness, resilience, anxiety, well-being and health-related quality of life; Exploratory outcomes - protein intake, behavioral beliefs around exercise and nutrition, adherence, adverse events, acceptability, and cost-utility. Conclusions The Heal-Me PiONEer RCT holds promise to provide a comprehensive understanding of the delivery and impact of app-based nutrition and exercise programming in a diverse group of participants with chronic disease.
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- 2022
41. Documenting patients' and providers' preferences when proposing a randomized controlled trial: a qualitative exploration
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Kathleen Reynolds, Susan Horsman, Sasha M. Lupichuk, Cynthia Kwok, Devesh Oberoi, Nicole Culos-Reed, Linda E. Carlson, Yong Li, Cindy Railton, Michael Speca, Anil A. Joy, Janine Giese-Davis, and Karen Marie King
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Epidemiology ,Aftercare ,Health Informatics ,Breast Neoplasms ,Medical Oncology ,law.invention ,Nursing ,Randomized controlled trial ,law ,Surveys and Questionnaires ,Humans ,Female ,Survivors ,Psychology - Abstract
Background With advances in cancer diagnosis and treatment, women with early-stage breast cancer (ESBC) are living longer, increasing the number of patients receiving post-treatment follow-up care. Best-practice survivorship models recommend transitioning ESBC patients from oncology-provider (OP) care to community-based care. While developing materials for a future randomized controlled trial (RCT) to test the feasibility of a nurse-led Telephone Survivorship Clinic (TSC) for a smooth transition of ESBC survivors to follow-up care, we explored patients’ and OPs’ reactions to several of our proposed methods. Methods We used a qualitative study design with thematic analysis and a two-pronged approach. We interviewed OPs, seeking feedback on ways to recruit their ESBC patients for the trial, and ESBC patients, seeking input on a questionnaire package assessing outcomes and processes in the trial. Results OPs identified facilitators and barriers and offered suggestions for study design and recruitment process improvement. Facilitators included the novelty and utility of the study and simplicity of methods; barriers included lack of coordination between treating and discharging clinicians, time constraints, language barriers, motivation, and using a paper-based referral letter. OPs suggested using a combination of electronic and paper referral letters and supporting clinicians to help with recruitment. Patient advisors reported satisfaction with the content and length of the assessment package. However, they questioned the relevance of some questions (childhood trauma) while adding questions about trust in physicians and proximity to primary-care providers. Conclusions OPs and patient advisors rated our methods for the proposed trial highly for their simplicity and relevance then suggested changes. These findings document processes that could be effective for cancer-patient recruitment in survivorship clinical trials.
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- 2021
42. Optimising weight-loss interventions in cancer patients-A systematic review and network meta-analysis
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Wei Cheng, Dianna Wolfe, Brian Hutton, Mona Hersi, Nadera Ahmadzai, Risa Shorr, Pauline Barbeau, Nathalie LeVasseur, Mark Clemons, Sasha Mazzarello, Lee W. Jones, Anil A. Joy, John Hilton, Carol Stober, and Lisa Vandermeer
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Physiology ,Cancer Treatment ,Psychological intervention ,law.invention ,Randomized controlled trial ,law ,Weight loss ,Neoplasms ,Medicine and Health Sciences ,Public and Occupational Health ,Intervention Duration ,Randomized Controlled Trials as Topic ,Multidisciplinary ,Anthropometry ,Prostate Cancer ,Prostate Diseases ,Prognosis ,Sports Science ,Physiological Parameters ,Oncology ,Meta-analysis ,Medicine ,Anatomy ,medicine.symptom ,Research Article ,medicine.medical_specialty ,Waist ,Urology ,Science ,Internal medicine ,Weight Loss ,medicine ,Humans ,Sports and Exercise Medicine ,Exercise ,Life Style ,Nutrition ,business.industry ,Body Weight ,Biology and Life Sciences ,Cancers and Neoplasms ,Physical Activity ,Diet ,Genitourinary Tract Tumors ,Physical Fitness ,business ,Body mass index - Abstract
Background Excess weight has been associated with increased morbidity and a worse prognosis in adult patients with early-stage cancer. The optimal lifestyle interventions to optimize anthropometric measures amongst cancer patients and survivors remain inconsistent. Objective To conduct a systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing the effects of exercise and dietary interventions alone or in combination on anthropometric measures of adult cancer patients and survivors. Methods A systematic search of Medline, Embase and the Cochrane Trials Registry was performed. Outcomes of interest included changes in weight, body mass index (BMI), and waist circumference. Screening and data collection were performed by two reviewers. Bayesian NMAs were performed. Results Overall, 98 RCTs were included; 75 were incorporated in NMAs (n = 12,199). Groups of intervention strategies included: 3 exercise interventions, 8 dietary interventions, 7 combination interventions of diet and exercise and standard care. Median intervention duration was 26 weeks. NMA suggested that diet alone (mean difference [MD] -2.25kg, 95% CrI -3.43 to -0.91kg) and combination strategies (MD -2.52kg, 95% CrI -3.54 to -1.62kg) were associated with more weight loss compared to standard care. All dietary interventions achieved a similar magnitude of weight loss (MD range from -2.03kg to -2.52kg). Both diet alone and combination strategies demonstrated greater BMI reductions versus standard care, and each of diet alone, exercise alone and combination strategies demonstrated greater reductions in waist circumference than standard care. Conclusion Diet and exercise alone or in combination are effective lifestyle interventions to improve anthropometric measures in cancer patients and survivors. All reputable diets appear to be similarly effective to achieve weight loss.
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- 2021
43. Uridine Glucuronosyltransferase 2B7 Polymorphism-Based Pharmacogenetic Dosing of Epirubicin in FEC Chemotherapy for Early-Stage Breast Cancer
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Sarah F. Cook, Anil A. Joy, Ann Vlahadamis, Karen King, Vijaya L. Damaraju, Avalyn Stanislaus, Larissa J. Vos, Michael B. Sawyer, Judith Meza-Junco, Edith Pituskin, Sanraj Basi, Robert R. Bies, Sambasivarao Damaraju, and John R. Mackey
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0301 basic medicine ,Adult ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Antineoplastic Agents ,Breast Neoplasms ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Internal medicine ,Genotype ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Glucuronosyltransferase ,Cyclophosphamide ,Epirubicin ,Chemotherapy ,Leukopenia ,Polymorphism, Genetic ,business.industry ,Middle Aged ,medicine.disease ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Toxicity ,Female ,medicine.symptom ,business ,Pharmacogenetics ,Febrile neutropenia ,medicine.drug - Abstract
Background Epirubicin is metabolized by uridine glucuronosyltransferase 2B7 (UGT2B7). Patients homozygous for the minor allele (CC) in the UGT2B7 -161 promoter polymorphism have lower clearance and significantly higher rates of leukopenia compared to wild-type homozygote (TT) or heterozygote (CT) patients. This study was designed to determine if TT and CT genotype patients could tolerate a higher epirubicin dose compared to CC genotype patients. Patients and Methods We studied women with histologically confirmed non-metastatic, invasive breast cancer who were scheduled to receive at least three cycles of FE100C in the (neo)adjuvant setting. Patients received standard-dose FE100C during the first 21-day cycle. Based on genotype, the epirubicin dose was escalated in the second and third cycles to 115 and 130 mg/m2 or to 120 and 140 mg/m2 for CT and TT genotype patients, respectively. The main outcome measurements were myelosuppression and dose-limiting toxicity. These were analyzed for relationships with the three genotypes. Results Forty-five patients were enrolled (10 CC, 21 CT, and 14 TT genotypes) and received 100 mg/m2 of epirubicin in the first cycle. Twelve and 10 TT patients were dose escalated at the second and third cycles, respectively; 16 CT patients were dose escalated at the second and third cycles. Leukopenia, but not febrile neutropenia, was genotype and dose dependent and increased in patients with CT and TT genotypes as their dose was increased. However, the third-cycle leukopenia rates were comparable to patients with the CC genotype receiving standard-dose epirubicin. Conclusion Pharmacogenetically guided epirubicin dosing is well tolerated and allowed dose escalation without increased toxicity.
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- 2020
44. Frequency, Timing, and Predictors of Palliative Care Consultation in Patients with Advanced Cancer at a Tertiary Cancer Center: Secondary Analysis of Routinely Collected Health Data
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Alysa Fairchild, Konrad Fassbender, Anil Abraham Joy, Asifa Mawani, Viane Faily, Sharon M. Watanabe, Karen M. King, Ann Huot, Vickie E. Baracos, Yoko Tarumi, A. B. Potapov, Christopher P. Venner, and Wilson Roa
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Adult ,Cancer Research ,medicine.medical_specialty ,Canada ,Palliative care ,Logistic regression ,03 medical and health sciences ,0302 clinical medicine ,Secondary analysis ,Neoplasms ,medicine ,Humans ,In patient ,030212 general & internal medicine ,Referral and Consultation ,Retrospective Studies ,business.industry ,Medical record ,Palliative Care ,Cancer ,medicine.disease ,Advanced cancer ,Cancer registry ,Oncology ,Symptom Management and Supportive Care ,030220 oncology & carcinogenesis ,Family medicine ,business ,Routinely Collected Health Data - Abstract
Introduction Early integration of palliative care (PC) with oncological care is associated with improved outcomes in patients with advanced cancer. Limited information exists on the frequency, timing, and predictors of PC consultation in patients receiving oncological care. The Cross Cancer Institute (CCI) is the sole tertiary cancer center serving the northern half of the Canadian province of Alberta, located in the city of Edmonton. The objectives of this study were to estimate the proportion of patients with advanced cancer at the CCI who received consultation by the CCI PC program and the comprehensive integrated PC program in Edmonton, and to determine the timing and predictors of consultation. Materials and Methods In this secondary analysis of routinely collected health data, adult patients who died between April 2013 and March 2014, and had advanced disease while under the care of a CCI oncologist, were eligible. Data from the Alberta Cancer Registry, electronic medical records, and Edmonton PC program database were linked. Results Of 2,253 eligible patients, 810 (36%) received CCI PC consultation. Median time between consultation and death was 2 months (range, 1.1–5.4). In multivariable logistic regression analysis, age, residence, income, cancer type, and interval from advanced cancer diagnosis to death influenced odds of receiving consultation. Among 1,439 patients residing in Edmonton, 1,121 (78%) were referred to the Edmonton PC program. Conclusion A minority of patients with advanced cancer received PC consultation at the tertiary cancer center, occurring late in the disease trajectory. Frequency and timing of PC consultation varied significantly, according to multiple factors. Implications for Practice Clinical and demographic factors are associated with variations in frequency and timing of palliative care consultation at a cancer center and may, in some cases, reflect barriers to access that warrant attention.
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- 2020
45. A Practical Approach to Using Integrated Knowledge Translation to Inform a Community-Based Exercise Study
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Christopher M. Sellar, Kirsten Suderman, S. Nicole Culos-Reed, Anil Abraham Joy, Naomi Dolgoy, Margaret L. McNeely, Kathryn C. Nishimura, and Janice L. Yurick
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Male ,knowledge translation ,Referral ,Health, Toxicology and Mutagenesis ,barriers ,Stakeholder engagement ,lcsh:Medicine ,Article ,law.invention ,Alberta ,Translational Research, Biomedical ,03 medical and health sciences ,0302 clinical medicine ,Nursing ,Randomized controlled trial ,Cancer Survivors ,law ,Knowledge translation ,Health care ,Humans ,cancer ,physical therapy ,Survivors ,implementation ,Community based ,Cancer survivor ,Descriptive statistics ,exercise ,business.industry ,lcsh:R ,Public Health, Environmental and Occupational Health ,030229 sport sciences ,030220 oncology & carcinogenesis ,Female ,business ,Psychology - Abstract
Background: Our aim was to understand cancer survivor needs prior to, and following the Alberta Cancer Exercise (ACE) pilot randomized trial as a means to inform implementation of a province-wide cancer-specific, community-based exercise program. Methods: Questionnaires and semi-structured stakeholder engagement sessions were conducted with cancer survivors to explore preferences, barriers and facilitators/benefits at two timepoints: (1) pre-ACE: prior to initiation of the ACE pilot trial (n = 13 survivors and n = 5 caregivers), and (2) post-ACE: following participation in the ACE pilot trial (n = 20 survivors). Descriptive statistics were used to summarize quantitative data from questionnaires. Stakeholder engagement data were analyzed using a framework analysis approach. Emergent themes were then mapped to actionable outcomes. Results: Pre-ACE, survivors indicated a preference for exercise programs that were (1) supervised by exercise specialists knowledgeable about cancer, (2) included support from other health care providers, (3) were held in community locations that were easily accessible. Post-ACE, participants identified (1) a lack of exercise counseling from health care providers, (2) the need for earlier introduction of exercise in the care pathway, and (3) supported referral to exercise programming. Conclusions: An integrated knowledge translation approach identified actionable outcomes to address survivor needs related to exercise in clinical cancer and community-based contexts.
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- 2020
46. A randomised trial of 4- versus 12-weekly administration of bone-targeted agents in patients with bone metastases from breast or castration-resistant prostate cancer
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Christina Canil, Christopher M. Booth, Ahwon Jeong, Igal Kushnir, Dean Fergusson, Phillip S. Blanchette, Mihaela Mates, Michael Ong, Scott Ernst, John Hilton, Anil A. Joy, Andrew Robinson, Lisa Vandermeer, Mark Clemons, Sasha Mazzarello, Gregory R. Pond, Olexiy Aseyev, Carol Stober, REaCT investigators, and Brian Hutton
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0301 basic medicine ,Oncology ,Male ,Cancer Research ,medicine.medical_specialty ,Bone Neoplasms ,Breast Neoplasms ,Drug Administration Schedule ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Breast cancer ,breast cancer ,Quality of life ,Internal medicine ,Clinical endpoint ,medicine ,Humans ,bone metastasis ,Aged ,Bone Density Conservation Agents ,business.industry ,zoledronate ,Cancer ,Bone metastasis ,denosumab ,Middle Aged ,medicine.disease ,prostate cancer ,Clinical Trial ,Confidence interval ,humanities ,3. Good health ,pamidronate ,Prostatic Neoplasms, Castration-Resistant ,030104 developmental biology ,Denosumab ,030220 oncology & carcinogenesis ,Female ,business ,medicine.drug - Abstract
Background Optimal dosing of bone-targeted agents (BTAs), in patients with bone metastases remains an important clinical question. This trial compared 4-weekly versus 12-weekly therapy. Patients and methods Patients with bone metastases from breast or castration-resistant prostate cancer (CRPC), who were going to start or already on BTAs, were randomised 1:1 to 4-weekly or 12-weekly BTA treatment for one year. Primary end point was change in health-related quality of life (HRQoL)-physical function European Organisation for Research and Treatment of Cancer (EORTC)-QLQ-C30). Secondary end points included pain (EORTC-QLQ-BM22), global health status (EORTC-QLQ-C30), symptomatic skeletal events (SSEs) rates and time to SSEs. Primary analysis was per protocol and a non-inferiority margin of 5 points was used. Results Of 263 patients (160 breast cancer, 103 CRPC), 133 (50.6%) and 130 (49.4%) were randomised to the 4- and 12-weekly groups, respectively. BTAs included denosumab (56.3%), zoledronate (24.0%) and pamidronate (19.8%). Using repeated-measures analysis, across all time points, patients in the 4-weekly arm had a mean HRQL-physical subdomain score which was 1.2 (95% confidence interval: -1.6 to 4.0) higher than the 12-weekly arm. The study met the definition of non-inferiority for our primary outcome. Secondary outcomes showed no significant difference in scores for pain, global health status, SSE rates and SSE-free survival between arms. Subgroup analyses for cancer type, prior BTA use or BTA type showed no significant difference between arms. Conclusion These results in addition to those previously reported for de-escalating zoledronate and systematic reviews in both breast and prostate cancers, would support that de-escalation of commonly used BTAs is a reasonable treatment option., Highlights • Four- versus 12-weekly therapy of bone-targeting agents in patients with bone metastases from breast or prostate cancer. • BTAs used in the study are pamidronate, zoledronate and denosumab. • Twelve-weekly therapy was non-inferior to 4-weekly therapy for the primary outcome of health-related quality of life. • No significant difference was seen in symptomatic skeletal event (SSE) rates and SSE-free survival between arms. • Results consistent with previous studies, suggests that de-escalation of BTAs is a reasonable treatment option.
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- 2020
47. Positive progress: current and evolving role of immune checkpoint inhibitors in metastatic triple-negative breast cancer
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Deanna McLeod, Christine Brezden-Masley, Anil Abraham Joy, Joy McCarthy, and Christine E. Simmons
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business.industry ,medicine.medical_treatment ,Immune checkpoint inhibitors ,Anti pd 1 ,Breast cancer subtype ,Immunotherapy ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,lcsh:RC254-282 ,Breast cancer ,Oncology ,Atezolizumab ,medicine ,Cancer research ,business ,Triple-negative breast cancer - Abstract
Background: Triple-negative breast cancer (TNBC) represents an aggressive breast cancer subtype with historically poor overall outcomes, due primarily to a lack of effective targeted agents. Chemotherapy has been the primary treatment approach, although immune checkpoint inhibitors (ICIs) are currently being investigated to improve patient outcomes. This review examines the clinical implications of current evidence on the use of ICIs for the treatment of metastatic TNBC. Methods: Our systematic search identified two phase III and five phase I/II trials reporting on the efficacy of ICIs used as monotherapy or combined with chemotherapy for the treatment of metastatic TNBC. Results: The phase III IMpassion 130 trial showed a significant improvement in median progression-free survival in the intent-to-treat (net 1.7 months, p = 0.002) and PD-L1-positive populations (net 2.5 months, p Conclusions: Atezolizumab plus nab-paclitaxel represents a potential new first-line standard of care for patients with metastatic PD-L1-positive TNBC. Other ICIs used as monotherapy, or combined with chemotherapy for advanced TNBC, as well as their use for earlier stage disease, are areas of ongoing investigation.
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- 2020
48. Palbociclib plus endocrine therapy in older women with HR+/HER2– advanced breast cancer: a pooled analysis of randomised PALOMA clinical studies
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Stephen R. D. Johnston, Xin Huang, Hope S. Rugo, Wan Sun, Patrick Schnell, Richard S. Finn, Sunil Verma, Nadia Harbeck, Shrividya Iyer, Seock-Ah Im, Cynthia Huang Bartlett, Sindy T. Kim, Nicholas C. Turner, Norikazu Masuda, and Anil A. Joy
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Pyridines ,Receptor, ErbB-2 ,Breast Neoplasms ,Palbociclib ,Disease-Free Survival ,Piperazines ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Double-Blind Method ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Fulvestrant ,Aged ,Randomized Controlled Trials as Topic ,business.industry ,Letrozole ,Incidence (epidemiology) ,Hazard ratio ,Cancer ,medicine.disease ,Confidence interval ,030104 developmental biology ,Receptors, Estrogen ,030220 oncology & carcinogenesis ,Quality of Life ,Female ,business ,medicine.drug - Abstract
Because incidence of breast cancer and comorbidities increase with age, it is important to determine treatment benefit in elderly patients. We evaluated outcomes with palbociclib plus endocrine therapy in patients aged ≥65 years.Data were pooled from three randomised studies (NCT00721409, NCT01740427 and NCT01942135) of women with HR+/HER2- advanced breast cancer (ABC). In PALOMA-1 (open-label) and PALOMA-2 (double-blind, placebo-controlled), treatment-naïve patients received palbociclib plus letrozole or letrozole alone. In PALOMA-3 (double-blind, placebo-controlled), patients with endocrine-resistant disease received palbociclib plus fulvestrant or fulvestrant alone.Among 528 patients treated with palbociclib plus letrozole and 347 treated with palbociclib plus fulvestrant, 218 (41.3%) and 86 (24.8%), respectively, were aged ≥65 years. Versus endocrine therapy alone, median progression-free survival was significantly improved in patients aged 65-74 years (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.45-0.97; P = 0.016) and ≥75 years (HR, 0.31; 95% CI, 0.16-0.61; P0.001) receiving palbociclib plus letrozole and in patients aged 65-74 years (HR, 0.27; 95% CI, 0.16-0.48; P0.001) receiving palbociclib plus fulvestrant; few patients aged ≥75 years received palbociclib plus fulvestrant (HR, 0.59; 95% CI, 0.19-1.8; P = 0.18). Patient-reported functioning and quality of life was maintained. No clinically relevant differences in palbociclib exposure were observed between age groups. Although myelosuppression was more common among patients aged ≥75 years, incidence of grade ≥III myelosuppression was similar across age groups, and febrile neutropenia was uncommon (≤2.4%); no new safety concerns were identified in older patients.Palbociclib plus endocrine therapy is an effective, well-tolerated treatment for older patients with ABC.
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- 2018
49. Feasibility of using a pragmatic trials model to compare two primary febrile neutropenia prophylaxis regimens (ciprofloxacin versus G-CSF) in patients receiving docetaxel-cyclophosphamide chemotherapy for breast cancer (REaCT-TC)
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Anil A. Joy, Carol Stober, John Hilton, Julie Price-Hiller, Brian Hutton, Anne Kehoe, Xiaofu Zhu, Ranjeeta Mallick, Mark Clemons, Sasha Mazzarello, Mohammed F.K. Ibrahim, Lisa Vandermeer, Marta Sienkiewicz, Shailendra Verma, and Dean Fergusson
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Adult ,medicine.medical_specialty ,medicine.medical_treatment ,Breast Neoplasms ,Filgrastim ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Patient satisfaction ,Ciprofloxacin ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Granulocyte Colony-Stimulating Factor ,medicine ,Clinical endpoint ,Humans ,030212 general & internal medicine ,Febrile Neutropenia ,Chemotherapy ,business.industry ,Antibiotic Prophylaxis ,Middle Aged ,medicine.disease ,Discontinuation ,Primary Prevention ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,Feasibility Studies ,Female ,business ,Febrile neutropenia ,medicine.drug - Abstract
Optimal primary febrile neutropenia (FN) prophylaxis (i.e. ciprofloxacin or granulocyte-colony stimulating factors [G-CSF]) for patients receiving docetaxel-cyclophosphamide (TC) chemotherapy is unknown. We assessed the feasibility of using a novel pragmatic comparative effectiveness trial to compare these standard-of-care options. Early-stage breast cancer patients receiving TC chemotherapy were randomised to either ciprofloxacin or G-CSF. Trial methodology consists of broad eligibility criteria, simply-defined endpoints, integrated consent model incorporating oral consent, and web-based randomisation in the clinic. Primary feasibility endpoints included patient and physician engagement (if > 50% of patients approached agree to participate and if > 50% of physicians approached patients for the study). Secondary clinical endpoints included the following: first occurrence rates of FN, treatment-related hospitalisation, or chemotherapy dose reduction/delay/discontinuation, as well as patient satisfaction with the oral consent process. Of 204 patients approached, 91.2% (186/204) agreed to randomisation. Sixteen of twenty (80%) participating medical oncologists randomised patients. Median patient age was 57.7 (range 31.8–84.1). The 186 patients received 557 cycles of chemotherapy. Overall incidences of first events by patient (n = 186) were as follows: FN (18/186, 21.43%), treatment-related hospitalisation (11/186, 13.10%), chemotherapy reduction (19/186, 22.62%), chemotherapy discontinuation (16/186, 19.05%), and chemotherapy delays (5/186, 5.95%). A total of 37.77% (69/186) of patients and 12.39% (69/557) of chemotherapy cycles had at least one of these first events. Patients were highly satisfied with the oral consent process. This study met its feasibility endpoints. This model offers a means of comparing standard-of-care treatments in a practical and cost-efficient manner. Trial registration: ClinicalTrials.gov : NCT02173262
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- 2018
50. Abstract P5-21-03: Palbociclib (PAL) + letrozole (LET) as first-line therapy in estrogen receptor–positive (ER+)/human epidermal growth factor receptor 2–negative (HER2−) advanced breast cancer (ABC): Efficacy and safety updates with longer follow-up across patient subgroups
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Johannes Ettl, HS Rugo, Eric Gauthier, A. Mori, Aurelio Castrellon, Karen A. Gelmon, C-S Huang, Oleg Lipatov, Nadia Harbeck, DJ Slamon, Anil A. Joy, Richard S. Finn, and Véronique Diéras
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,education.field_of_study ,business.industry ,medicine.drug_class ,Letrozole ,Population ,Estrogen receptor ,Cancer ,Phases of clinical research ,Palbociclib ,medicine.disease ,030227 psychiatry ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Estrogen ,030220 oncology & carcinogenesis ,Internal medicine ,Medicine ,business ,education ,medicine.drug - Abstract
BACKGROUND: Endocrine therapy (ET) has been the primary first-line (1L) therapy for ER+ ABC. In the PALOMA-2 study (NCT01740427), PAL (P)+LET (L) significantly prolonged progression-free survival (PFS; HR=0.58, P METHODS: Postmenopausal pts w/ ER+/HER2- ABC and no prior systemic therapy in the ABC setting were randomized 2:1 to P (125 mg/d) + L (2.5 mg QD) or placebo (PBO) + L. Key endpoints: investigator-assessed PFS and safety. Median PFS (mPFS) was estimated (intent-to-treat population). RESULTS: 666 pts (444, P+L; 222, PBO+L) were enrolled. Arms were well balanced: visceral (48%)/nonvisceral (52%) disease and prior ET (56%)/no prior ET (44%). After a median FU of 38 mo w/ P+L and 37 mo w/ PBO+L, mPFS was 27.6 and 14.5 mo, respectively, in the overall population (HR=0.56, P TABLE. mPFS overall and by relevant subgroupsP+LPBO+LP+L vs PBO+LmPFS, mo (95% CI)mPFS, mo (95% CI)HR (95% CI)P* Overall27.6 (22.4–30.3)14.5 (12.3–17.1)0.56 (0.46–0.69) All subgroups benefited from addition of P to L. Notably, pts w/ low disease burden (bone only, nonvisceral disease, few disease sites) derived significant PFS benefit, including those w/ both nonvisceral disease and no prior ET (mPFS, 36.2 vs 27.6 mo; HR=0.59, P CONCLUSIONS: This is the longest FU of a phase 3 study of a cyclin-dependent kinase 4/6 inhibitor for ABC. P+L continues to consistently improve PFS vs PBO+L across all subgroups while toxicity remains manageable; notably P+L delays time to starting 2nd subsequent anticancer therapies by 10 mo. Pts w/ low disease burden or sensitivity to ET alone had PFS >3 y (significant vs PBO+L), demonstrating the clinical benefit of P+ET. These data confirm P+L should be a 1L therapy option for pts w/ HR+/HER2- ABC. Funding: Pfizer Citation Format: Rugo HS, Finn RS, Dieras V, Ettl J, Lipatov O, Joy A, Harbeck N, Castrellon A, Lu DR, Mori A, Gauthier ER, Huang C, Gelmon KA, Slamon DJ. Palbociclib (PAL) + letrozole (LET) as first-line therapy in estrogen receptor–positive (ER+)/human epidermal growth factor receptor 2–negative (HER2−) advanced breast cancer (ABC): Efficacy and safety updates with longer follow-up across patient subgroups [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-21-03.
- Published
- 2018
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