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Introduction: Cancer-related fatigue (CRF) is a common symptom in patients with metastatic breast cancer (MBC), who receive taxane-based chemotherapy, and is associated with poor outcomes. Current guidelines recommend regular screening for fatigue from the time of cancer diagnosis, during treatment, and after treatment is completed to identify CRF early, lessen its negative impact on quality of life, and prevent potential treatment interruptions. Fatigue is a subjective symptom and is assessed through patient questionnaires such as the FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) survey. However, there is currently no gold standard or recommended survey to assess CRF. Methods: A prospective, non-interventional, multicenter trial is ongoing to validate the FACIT-Fatigue scale in patients with locally advanced or metastatic breast cancer who are eligible to receive taxane-based chemotherapy. Adult patients who have documented locally advanced or metastatic breast cancer (not amenable to surgical resection), and mild-to-moderate CRF indicated by a score of 1 to 6 on a scale from 0 to 10 (10 being most severe), who are candidates to receive cycle one of taxane chemotherapy will be included. Patients who are unable to take oral medications, have other cancer-related causes of fatigue, are using oral morphine ≥60 mg/day, or are participating in another clinical trial will be excluded. The primary objective is to evaluate the change in FACIT-Fatigue scores at baseline and at the end of the study (16 weeks). Secondary endpoints include evaluation of quality-of-life outcomes. A subgroup of patients will participate in a phone-based cognitive interview at the end of study visit or within 2 weeks of this visit to explore fatigue factors deemed important to patients. Results: The total planned sample size is estimated to be 60 patients to allow for a minimum clinically important difference (MCID) with a minimum precision of 1.9 points, and standard deviation of 3 points. The qualitative assessment will be conducted as part of a substudy inclusive of data from 30 patients. Conclusions: This study is currently ongoing to determine the MCID in FACIT-Fatigue scores in patients with locally advanced or MBC receiving treatment with taxane-based chemotherapy. Contact usmedinfo@dompe.com for information related to clinical trial sites and this study. Citation Format: Alessandra Fabi, Steven Hager, Laura Lourdes, Rebecca Pedersini, Paola Malaguti, Elizabeth M. Gavioli, Renuka Wakade, Pier Adelchi Ruffini, Francesco Sergio, Manuela Leone, Flavio Mantelli, Marcello Allegretti, Anne Blaes. Trial In Progress: An Evaluation of FACIT-Fatigue in Patients with Locally Advanced or Metastatic Breast Cancer receiving Treatment with Taxane-based Chemotherapy [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 OT1-16-01.

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Among pre- and postmenopausal women with hormone receptor-positive (HR+) breast cancer (BC), combinations of an aromatase inhibitor (AI) or fulvestrant with a CDK 4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) have demonstrated improved progression-free survival (PFS) and overall survival (OS) compared to standard single-agent hormone therapy alone as first-line therapy for de novo metastatic disease or relapse during or after adjuvant therapy and no previous therapies in an advanced setting. We here reviewed clinical data about ribociclib in advanced and early BC. Also, we shed light on patient selection and special settings in which medical oncologists urgently await an advance in treatment. Ribociclib was FDA-approved in combination with letrozole based on a Phase III study in which 668 postmenopausal women with HR+, HER2-negative recurrent or metastatic BC were treated with first-line letrozole with or without ribociclib. For patients with metastatic disease at presentation or after a course of AIs, the results of the MONALEESA-3 trial suggest ribociclib's efficacy in combination with fulvestrant, and this combination is FDA-approved for initial- and subsequent-line endocrine therapy for postmenopausal women with metastatic hormone receptor-positive, HER2-negative BC. In adjuvant and neoadjuvant settings, the use of CDK 4/6 inhibitors may be useful to boost outcomes in high-risk patients with HR+ BC, but data contrast with those of a phase III study, which produced positive results. New combinations are being explored in upfront disease (neoadjuvant) or in association with other targeted agents in metastatic disease. Compared to other CDK 4/6 available, ribociclib has a higher incidence of liver function test abnormalities than the other agents and can cause QTc prolongation, and therefore may be prudently avoided in patients with cardiac morbidities or other risk factors for QTc prolongation (drugs, interactions). In these cases, different agents (palbociclib or abemaciclib) may be used. In conclusion, ribociclib with letrozole or with fulvestrant is effective for the entire spectrum of patients with HR+ BC in the advanced setting. Ribociclib has all the characteristics of an innovative drug able to change the clinical practice and most BC patients' prognoses.

Introduction. Antibody-drug conjugates (ADCs) represent a new class of molecular-targeted drugs, which are being developed to selectively target tumor cells and minimize toxicities. Three ADCs, namely trastuzumab emtansine (TDM-1), sacituzumab govitecan, and trastuzumab deruxtecan, are currently approved for the treatment of metastatic breast cancer (MBC). Acute gastrointestinal toxicities are relatively frequent with these agents. We performed a pooled analysis evaluating gastrointestinal adverse events (AEs) in patients with MBC treated with ADCs. Methods. PubMed, Embase, and the Cochrane Library were searched from inception until December 2020 for phase 2 and 3 trials reporting frequency and severity of gastrointestinal AEs in patients treated with ADCs. Data were collected for nausea, vomiting, diarrhea, constipation, and abdominal pain: overall and grade 3-4 toxicity rates according to NCI-CTCAE were described and expressed as proportions. A pre-specified subgroup analysis according to type of agent was also performed. Results. Ten studies, involving a total of 4020 patients, were included in the analysis. Gastrointestinal AEs were very frequent with sacituzumab govitecan and trastuzumab deruxtecan but were mostly low-grade. These novel ADCs were characterized by a significantly higher incidence of nausea (65.6% with sacituzumab govitecan, 77.2% with trastuzumab deruxtecan), vomiting (43.7% and 46.6%), and diarrhea (59.7% and 30.2%) compared to TDM-1. Diarrhea was the main AEs associated with sacituzumab govitecan (grade 3 in 7.5% of patients). Abdominal pain and constipation were reported less frequently. Conclusions. Gastrointestinal AEs, especially nausea and diarrhea, are common in patients with MBC treated with novel ADCs. Prevention and treatment of these side effects are essential to maintain the dose intensity of ADCs and optimize the treatment compliance of patients. Table. Gastrointestinal toxicities of the different ADCs in MBC patients in the current pooled analysis.Gastrointestinal toxicities Toxicity pooled % (CI 95%)Sacituzumab govitecanTDM-1Trastuzumab deruxtecanp*p**p#NauseaAll gradesG3-G457.8 (46.9-68)2.2 (1-4.9)65.6 (61-70)4.3 (2.2-8.3)38.1 (32-44.5)0.8 (0.5-1.2)77.2 (72-81.6)2.6 (0.2-30.6)< 0.01< 0.01< 0.01< 0.01< 0.010.71DiarrheaAll grades G3-G434 (21.8-48.8)2.4 (1.7-3.3)59.7 (52.4-66.6)7.5 (4.3-12.7)17.5 (11.-25.4)0.9 (0.6-1.6)30.2 (25.3-35.7)2.4 (1.1-4.9)< 0.01< 0.01< 0.010.03< 0.010.015VomitingAll grades G3-G432.5 (23.6-42.8)2.7 (1.4-5)43.7 (33.5-54.5)4.4 (1.7-10.8)18.2 (15.3-21.4)1.3 (0.9-1.8)46.6 (41-52.3)4.4 (2.5-7.4)< 0.01< 0.01< 0.01< 0.01NSNSAbdominal painAll grades G3-G414.8 (9.4-22.5)1.2 (0.7-2.1)20.1 (11.9-31.8)1.3 (0.4-3.9)6.2 (4.2-9)1.2 (0.5-2.9)14.5 (9.8-21)0.9 (0.3-3.1)< 0.01NS< 0.01NSNSNSConstipationAll grades G3-G428.7 (20.4-38.9)0.6 (0.4-0.9)32.2 (18.6-49.6)0.8 (0.3-2.6)18 (12-26.1)0.5 (0.3-0.9)35.9 (30.7-41.5)0.7 (0.2-2.7)< 0.01NS< 0.01°NSNSNS* Statistically significant difference (p < 0.05) among the three ADCs.** Statistically significant difference (p < 0.05) for TDM-1 versus the other two ADCs.# Statistically significant difference (p < 0.05) for sacituzumab govitecan versus trastuzumab deruxtecan.° This value was not significant for T-DM1 versus sacituzumab govitecan comparison.CI, confidence interval; NS, not significant. Citation Format: Pierluigi di Mauro, Rebecca Pedersini, Fausto Petrelli, Antonio Ghidini, Vito Amoroso, Lara Laini, Maria Chiara Parati, Paolo Bossi, Alfredo Berruti. Gastrointestinal toxicity of antibody-drug conjugates (ADCs) in metastatic breast cancer: A pooled analysis [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 P5-18-15.

Introduction: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) are the standard first-line treatment for patients with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (HR+/HER2- aBC). HER2-low BC, which is defined by an IHC score for HER2 of 1+ or 2+ with negative ISH assay, accounts for more than half of all HR+/HER2- aBC cases, and it is associated with remarkable clinical benefit from the novel anti-HER2 antibody drug conjugate (ADC) trastuzumab-deruxtecan. Evidence on the prognostic impact of HER2-low status is controversial in both limited-stage and advanced BC. Here, we sought to investigate the possible prognostic relevance of HER2-low status in a population of aBC patients treated with CDK4/6i plus ET. Methods: We conducted a retrospective-prospective study in six Italian Cancer Centers to investigate the impact of HER2 status (low vs. 0) on the progression-free survival (PFS) and overall survival (OS) of consecutive HR+/HER2- aBC patients treated with CDK4/6i plus ET (aromatase inhibitors or fulvestrant) as a first-line therapy. In the main study analysis, we considered HER2 status in the last tumor assessment (i.e., primary tumor, or, when available, a metastatic lesion). We also performed a subgroup analysis including only patients with HER2 status evaluation in a metastatic lesion collected before CDK4/6i plus ET therapy initiation. The association between HER2 status (low vs. 0) and PFS or OS was evaluated using log-rank test and Cox regression modeling. Results: We evaluated 767 consecutive HR+/HER2- aBC patients treated with CDK4/6i plus ET between January 2017 and January 2022. Of these, 436 patients (56.8%) received CDK4/6i plus ET as a first-line therapy, and they were included in this analysis. Median age was 63 years (range 27-87), and 362 patients (83.0%) were postmenopausal. The majority of patients were treated with palbociclib (68.3%), while 91 (20.9%) and 47 (10.8%) patients received ribociclib and abemaciclib, respectively. Regarding HER2 status, 269 (62.9%) patients had HER2-low tumors, while 159 (37.1%) patients had HER2-0 neoplasms. HER2-low status was associated with significantly lower PFS when compared to HER2-0 status [median PFS (mPFS) 23.6 vs. 32.3 months, respectively; p=0.014]. HER2-low status was also associated with significantly worse OS (mOS 48.7 vs 58.3 months, respectively; p=0.025). These results were confirmed in multivariable models adjusting the impact of HER2 status for clinically-relevant covariates, namely estrogen receptor status, Ki-67, age, number of metastatic sites, presence of liver metastases, disease free interval, ECOG Performance Status. In this analysis, HER2-low status, compared with HER2-0 status, was independently associated with worse PFS [adjusted Hazard Ratio (aHR): 1.62; 95% confidence interval (CI): 1.17-2.24; p< 0.01] and OS (aHR: 1.74; 95% CI: 1.09-2.76; p=0.019). Subgroup analysis conducted in the subset of 256 patients with available metastatic tumor samples collected before CDK4/6i plus ET initiation confirmed that HER2-low status (n=157), when compared to HER2-0 status (n=99), was independently associated with worse PFS (mPFS 24.5 vs 35.2 months, p=0.01; aHR 2.07; 95% CI: 1.28-3.34, p< 0.01) and worse OS (mPFS 48.7 vs 72.3 months, p=0.027; aHR 3.12; 95% CI 1.44-6.77, p< 0.01). Conclusions: This multicenter Italian study revealed that HER2-low status has independent, negative prognostic value in patients with HR+/HER2- aBC treated with CDK4/6i plus ET in the first-line setting. Our results suggest that HER2-low status might be associated with different clinical benefit from standard anticancer therapies in specific clinical settings. The definition of treatment algorithms also taking into account HER2 status is a clinical priority in patients with HR+/HER2- aBC. Citation Format: Emma Zattarin, Caterina Sposetti, Rita Leporati, Luigi Mariani, Alice Menichetti, Chiara Corti, Chiara Benvenuti, Giovanni Fucà, Riccardo Lobefaro, Francesca Ligorio, Daniele Presti, Leonardo Provenzano, Andrea Vingiani, Gaia Griguolo, Marianna Sirico, Ottavia Bernocchi, Antonio Marra, Paola Zagami, Elisa Agostinetto, Flavia Jacobs, Pierluigi Di Mauro, Andrea Esposito, Carlo Alberto Giorgi, Luca Lalli, Laura Boldrini, Pier Paolo Maria Berton Giachetti, Ambra Carnevale Schianca, Valentina Guarneri, Rebecca Pedersini, Agnese Losurdo, Alberto Zambelli, Daniele Giulio Generali, Giuseppe Curigliano, Giancarlo Pruneri, Filippo de Braud, Maria Vittoria Dieci, Claudio Vernieri. HER2-02 HER2-Low Status is Associated with Worse Clinical Outcomes in Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer Patients Treated With First-Line Cyclin-Dependent Kinase 4/6 Inhibitors Plus Endocrine Therapy [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 HER2-02.

Bone-active drugs are recommended to protect the skeleton from detrimental actions of aromatase inhibitors (AIs). However, most of literature data are focused on bone mineral density (BMD), whereas data on fractures are scant. The aim of this prospective study was to investigate the real-life effectiveness of denosumab, oral bisphosphonates (BPs) and intravenous zoledronate on risk of vertebral fractures (VFs) induced by AIs. 567 consecutive women (median age 62 years, range 28-83) with early breast cancer undergoing treatment with AIs were evaluated for morphometric VFs and BMD at baseline and after 18-24 months of follow-up. After enrollment, 268 women (47.3%) started denosumab 60 mg subcutaneously every 6 months, 115 (20.3%) BPs (59 with oral BPs and, 56 with intravenous zoledronate 5 mg/12 months), whereas 184 women (32.5%) were not treated with bone-active drugs for several reasons. During follow-up, 54 women (9.5%) developed incident VFs in association with age of subjects (P lt; 0.001), baseline FRAX scores for major fractures (P lt; 0.001) and hip fractures (P = 0.003), pre-existing VFs (P lt; 0.001), change in BMD at lumbar spine (P = 0.015), femoral neck (P = 0.003) and total hip (P lt; 0.001). Risk of VFs was higher in subjects who were untreated as compared to those treated with bone-active drugs (32/184 vs. 22/383; P lt; 0.001). Specifically, fracture risk was significantly decreased by denosumab [odds ratio (OR) 0.22; P lt; 0.001] and zoledronate (OR 0.27; P = 0.035), but not by oral BPs (P = 0.317). These data suggest that in real-world clinical practice, denosumab and zoledronate can reduce AI-related risk of VFs after only 24 months of treatment.

Purpose Eribulin mesylate (EM) is a non-taxane microtubule inhibitor approved for use in patients with metastatic breast cancer. With this pooled analysis of retrospective studies, we evaluated the efficacy and toxicity profile of EM in older patients with breast cancer in the real-world setting. Methods We performed a systematic database search for studies published up to March 2019 and reporting outcome and adverse events with EM in older patients (≥70 years). Overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) were described and aggregated in a pooled analysis. Main toxicity rates (G1-2 and G3-4) were also described. Results The analysis included five studies for a total of 301 patients. The median age was 71 to 74 years. Pooled ORR, median PFS and OS were 23.2%, 4.8 and 13.1 months, respectively. The disease control rate was 47%. Grade 3-4 neutropenia was 0 to 49%, G3-4 anemia and thrombocytopenia were rare. The most frequent G3-4 adverse events among non-hematological toxicities were fatigue (5-16.5%) and neurotoxicity (0-10.1%). Dose reduction rate was reported in three studies and carried out in 40% of patients (18.6-84%). Conclusions This pooled analysis shows that the median OS in older patients with breast cancer is 13 months, with an ORR of 23%. Control of disease was achieved in about 50% of patients. Dose reduction was relatively frequent and severe toxicities were rare. EM treatment of older patients with breast cancer is feasible and reflects the outcomes for the general population.

Dysgeusia and taste alterations (TAs) are side effects of cytotoxic chemotherapy and affect patients' quality of life; however, the prevalence, types, and duration of TAs and their potential relationship with other clinical disturbances are not well-described. Our primary aim was to prospectively evaluate the characteristics of TAs in early breast cancer (EBC) patients during (neo)adjuvant chemotherapy and up to 1 year after its completion.From April 2014 to June 2018, 182 EBC patients entered the study and received (neo)adjuvant chemotherapy, mostly with taxane and anthracycline-containing regimens (65% of cases). A dietitian performed TAs assessment through the Common Terminology Criteria for Adverse Event v4.0 (CTCAE) and the Chemotherapy-induced Taste Alteration Scale (CiTAS) questionnaire during chemotherapy and follow-up according to defined time points: at baseline (T0, before starting chemotherapy); at the first follow-up visit, (T1, 2 months after starting chemotherapy); at the final follow-up visit (T2, 1 week after completing chemotherapy); after that, every 3 months up to 12 months.Dysgeusia was reported by 69.8% of patients at T1 and declined subsequently; salty flavor distortion was the most frequently reported TA (51.6% of cases). CiTAS was significantly different between T0 and T2 (p 0.001). Dysgeusia occurred more frequently in patients reporting nausea, mucositis, diarrhea, and appetite modification.TAs are common but transient during chemotherapy and occurred frequently with other distressing gastrointestinal side effects. The assessment of these side effects is crucial in managing EBC patients during (neo)adjuvant chemotherapy.

ObjectiveTo evaluate the efficacy of clinical triage of oncological patients for safe continuation of cancer therapy implemented during the first SARS-CoV-2 outbreak.MethodsBetween 25 February and 21 April 2020, patients attending the Medical Oncology Unit, Spedali Civili Hospital, Brescia (Italy) for cancer therapy underwent triage to identify those with no signs and symptoms suspicious for SARS-CoV-2 infection in which antineoplastic treatment could be continued as scheduled. Triage questions investigated common symptoms (e.g., fever, cough, dyspnea, anosmia, dysgeusia, headache, nasal congestion, conjunctival congestion, sore throat, diarrhea, nausea and vomiting); body temperature and pulse oximetry were also recorded. All patients were followed-up for overt SARS-CoV-2 through to 18th May 2020.ResultsOverall, 1180 patients (median age 65 years) underwent triage during the study period. The most frequent primary malignances were breast (32%), gastrointestinal (18%), and lung (16.5%) cancer. Thirty-one (2.5%) presented with clinically evident SARS-CoV-2 infection and tested positive on nasopharyngeal swab testing and/or radiological imaging. Triage identified 69 (6%) grey zone patients with symptoms suspicious for SARS-CoV-2; 5 (7.2%) subsequently developed symptomatic disease. Neither the symptomatic nor the grey zone patients received their scheduled treatment; instead, they were referred for hospitalization or home quarantine.ConclusionTriage of oncological patients at our Unit provided for safe continuation of scheduled cancer treatment in 91.5% of patients during the initial SARS-CoV-2 outbreak.

Context Patients with adrenocortical carcinoma (ACC) are frequently on mitotane therapy for a long time period. The drug exerts adrenolytic activity requiring glucocorticoid supplementation, which can be potentially detrimental for bone. Objective To explore whether mitotane with/without chemotherapy is associated with an increased proportion of morphometric vertebral fractures (VFs) in ACC patients. Secondary objectives were proportion of patients with VF progression, or worsening of the spinal deformity index (SDI) during mitotane therapy; and to explore predictive factors of VF progression and a prognostic role of VF progression. Methods Multicenter, retrospective cohort study of patients with ACC who received mitotane alone or in association to chemotherapy, recruited from January 2010 to January 2020 in 2 reference centers in Italy and France. Results A significant increase in the frequency of VFs before and after mitotane therapy was seen both in Italian (28.3% vs 47.8%, P = .04) and French (17.8% vs 35.6%, P = .04) series. VF progression was observed in 39.1%, and 28.9% of patients, respectively. Baseline VFs and increased patient body mass index, but not the dose of cortisol supplementation, showed an independent association with VF progression at multivariate analysis. Among the 72 advanced ACC patients, progression of VFs was associated with a poorer survival. Conclusion The administration of mitotane with/without chemotherapy in ACC patients impairs bone health independently from cortisol supplementation. Appropriate preventive measures to decrease the fracture risk should be implemented in these patients.

Change in eating habits in early breast cancer (EBC) patients during chemotherapy has been poorly studied in the literature. The primary aim of this study was to prospectively evaluate food preferences and weight change in EBC patients before and after adjuvant chemotherapy. From April 2014 to June 2018, 205 EBC patients underwent a dietary assessment according to the following timeline: baseline evaluation (one week before starting chemotherapy, T0); first follow-up (approximately 2–3 months after starting chemotherapy, T1); final follow-up (one week after chemotherapy end, T2). A statistically significant reduction of the following foods was reported after the start of chemotherapy: pasta or rice, bread, breadsticks/crackers, red meat, fat and lean salami, fresh and aged cheese, milk, yogurt, added sugar, soft drinks, alcoholic beverages (wine, beer, and schnapps), and condiments (oil and butter). Conversely, fruit consumption consistently increased. As a result of these changes, a Healthy Eating Index (HEI) specifically developed for this study and suggestive of a balanced diet, significantly increased. Body weight did not increase, despite reduction in physical activity. This prospective study shows that EBC patients tend to adopt “healthier dietary patterns” during adjuvant chemotherapy, leading to a non-change in weight, despite reduction in physical activity.

Purpose: The mTOR complex C1 (mTORC1) inhibitor everolimus in combination with the aromatase inhibitor exemestane is an effective treatment for patients with hormone receptor—positive (HR+), HER2-negative (HER2−), advanced breast cancer (HR+/HER2− aBC). However, everolimus can cause hyperglycemia and hyperinsulinemia, which could reactivate the PI3K/protein kinase B (AKT)/mTORC1 pathway and induce tumor resistance to everolimus. Experimental Design: We conducted a multicenter, retrospective, Italian study to investigate the impact of baseline and on-treatment (i.e., during first 3 months of therapy) blood glucose levels on progression-free survival (PFS) in patients with HR+/HER2− aBC treated with everolimus-exemestane. Results: We evaluated 809 patients with HR+/HER2− aBC treated with everolimus-exemestane as any line of therapy for advanced disease. When evaluated as dichotomous variables, baseline and on-treatment glycemia were not significantly associated with PFS. However, when blood glucose concentration was evaluated as a continuous variable, a multivariable model accounting for clinically relevant patient- and tumor-related variables revealed that both baseline and on-treatment glycemia are associated with PFS, and this association is largely attributable to their interaction. In particular, patients who are normoglycemic at baseline and experience on-treatment diabetes have lower PFS compared with patients who are already hyperglycemic at baseline and experience diabetes during everolimus-exemestane therapy (median PFS, 6.34 vs. 10.32 months; HR, 1.76; 95% confidence interval, 1.15–2.69; P = 0.008). Conclusions: The impact of on-treatment glycemia on the efficacy of everolimus-exemestane therapy in patients with HR+/HER2− aBC depends on baseline glycemia. This study lays the foundations for investigating novel therapeutic approaches to target the glucose/insulin axis in combination with PI3K/AKT/mTORC1 inhibitors in patients with HR+/HER2− aBC.

Background The DigniCap System is an effective scalp cooling device for the prevention of chemotherapy-induced alopecia in early breast cancer patients. Aim This prospective study was designed to confirm the efficacy and tolerability of the device, to explore potential factors associated with its efficacy and to collect data on patient perceptions and satisfaction. Methods Between January 2016 and June 2018, 163 early breast cancer patients eligible for adjuvant chemotherapy were enrolled. Hair loss was assessed using the Dean scale, where a score of 0-2 (hair loss ≤50%) was defined as successful. Results Hair preservation was successful in 57% of patients in the overall series. The proportion was even higher (81%) in the patient subgroup treated with a paclitaxel and trastuzumab regimen. Side effects (feeling cold, headache, head heaviness, scalp and cervical pain) were mild to moderate and did not correlate with the rate of hair loss. Lifestyle, anthropometric factors and hair characteristics failed to be associated with device efficacy. Conclusions The DigniCap System was well tolerated and found to be effective in preventing alopecia in early breast cancer patients. Our study failed to identify factors other than type of chemotherapy regimen associated with hair preservation.

Background: During the SARS-COV-2 pandemic, cancer patients (pts) who are infected may develop severe disease if their systemic treatment is not temporarily stopped Nasopharyngeal swab was not extensively available to screen cancer pts for SARS-COV-2 infection in northern Italy, the most area in the country most affected by the pandemic From the beginning of the outbreak onwards, all pts admitted to the Medical Oncology Unit at Spedali Civili Hospital, Brescia, underwent a triage investigating the presence of symptoms and signs suggestive of SARS-COV-2 infection Triage results were used to decide which pts should continue antineoplastic treatments Methods: All consecutive cancer pts being admitted for systemic treatment from February 24th to April 21st 2020 were considered Triage, performed by a trained nurse, consisted of questions regarding the presence of fever, cough, dyspnea, anosmia, dysgeusia, headache, nasal congestion, conjunctival congestion, sore throat, diarrhoea, nausea and vomiting, measurement of body temperature and pulse oximetry All enrolled pts were followed-up for overt SARS-COV-2 development until May 18th Results: Overall, 1180 pts were included, 54% female and median age 65 years Most represented primary malignancies were breast (32%), gastroenteric (18%) and lung (16 5%) Thirty-one (2 5%) presented with clinically evident SARS-COV-2 disease and infection was proven by positive nasopharyngeal swab and/or radiological imaging The triage identified 69 (6%) “grey zone” pts, with suspicious symptoms (i e fever 41%, cough 30%, dyspnea 19%) The nasopharyngeal swab was negative in 48% of them and was not performed in the remaining 52% of pts, as well as in all pts who were triage negative Both SARS-COV-2 positive and “grey zone” pts did not receive treatment and were addressed to hospitalisation or home quarantine All the 1080 pts (91 5%) who resulted negative at triage continued their antineoplastic therapy as scheduled, none of them presenting symptoms of SARS-COV-2 infection during the follow-up Conclusions: Accurate triage allowed safe continuation of anticancer treatment in 91 5% of pts during the SARS-COV-2 outbreak Legal entity responsible for the study: The authors Funding: Has not received any funding Disclosure: All authors have declared no conflicts of interest

Patients with cancer are at a higher risk of developing serious disease-related complications in case of contracting SARS-CoV-2. Oncology units should implement all possible preventive measures to reduce the risk of viral transmission by healthcare professionals (HCPs) to patients. We conducted a surveillance for SARS-CoV-2 infection among the staff members of the Medical Oncology Unit of ASST Spedali Civili in Brescia, one of the Italian areas most affected by the SARS-CoV-2 pandemic. The aim of this study was to demonstrate whether the recommended preventive measures, promptly implemented by the unit, have been effective in reducing the spread of the virus among the HCPs. Between February 24 and May 19, 2020, SARS-CoV-2 infection was detected in 10 out of 76 healthy HCPs (13%). Six of them developed a symptomatic disease, leading to home quarantine, and four remained asymptomatic. The infection was revealed when a serology test was performed on all staff members of the unit. In seven HCPs, in which it was possible to trace the person-to-person infection, the contagion occurred as a result of unprotected contacts or partially protected with surgical masks. In particular, four asymptomatic HCPs did not stop working, but a widespread outbreak in the unit was avoided. Adherence to the recommended preventive strategies, in particular, wearing of surgical masks by both the HCPs and the patients, is effective in reducing and preventing the viral spread.

Background Limited data are available regarding the use of nab-paclitaxel in older patients with breast cancer. A weekly schedule is recommended, but there is a paucity of evidence regarding the optimal dose. We evaluated the efficacy of two different doses of weekly nab-paclitaxel, with a specific focus on their corresponding impact on patient function, in order to address the lack of data specifically relating to the older population. Methods EFFECT is an open-label, phase II trial wherein 160 women with advanced breast cancer aged ≥ 65 years were enrolled from 15 institutions within Italy. Patients were randomly assigned 1:1 to receive nab-paclitaxel 100 mg/m2 (arm A) or 125 mg/m2 (arm B) on days 1, 8, and 15 on a 28-day cycle, as first-line treatment for advanced disease. The primary endpoint was event-free survival (EFS), wherein an event was defined as disease progression (PD), functional decline (FD), or death. In each arm, the null hypothesis that the median EFS would be ≤ 7 months was tested against a one-sided alternative according to the Brookmeyer Crowley test. Secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), and safety. Results After a median follow-up of 32.6 months, 140 events were observed in 158 evaluable patients. Median EFS was 8.2 months (90% CI, 5.9–8.9; p = 0.188) in arm A vs 8.3 months (90% CI, 6.2–9.7, p = 0.078) in arm B. Progression-free survival, overall survival, and response rates were similar in both groups. A higher percentage of dose reductions and discontinuations due to adverse events (AEs) was noted in arm B. The most frequently reported non-haematological AEs were fatigue (grade [G] 2–3 toxicity occurrence in arm A vs B, 43% and 51%, respectively) and peripheral neuropathy (G2–3 arm A vs B, 19% and 38%, respectively). Conclusion Pre-specified outcomes were similar in both treatment arms. However, 100 mg/m2 was significantly better tolerated with fewer neurotoxicity-related events, representing a more feasible dose to be recommended for older patients with advanced disease. Trial registration EudraCT, 2012-002707-18. Registered on June 4, 2012. NIH ClinicalTrials.gov, NCT02783222. Retrospectively registered on May 26, 2016.

Cyclin dependent kinases 4/6 (CDK4/6) inhibitors gained an essential role in the treatment of metastatic breast cancer. Nevertheless, data regarding their use in combination with radiotherapy are still scarce. We performed a retrospective preliminary analysis of breast cancer patients treated at our Center with palliative radiation therapy and concurrent CDK4/6 inhibitors. Toxicities were measured according to CTCAE 4.0, local response according to RECIST 1.1 or PERCIST 1.0 and pain control using verbal numeric scale. 18 patients (32 treated sites) were identified; 50% received palbociclib, 33.3% ribociclib and 16.7% abemacliclib. Acute non-hematologic toxicity was fair, with the only exception of a patient who developed G3 ileitis. During 3 months following RT, 61.1% of patients developed G 3–4 neutropenia; nevertheless no patient required permanent suspension of treatment. Pain control was complete in 88.2% of patients three months after radiotherapy; 94.4% of patients achieved and maintained local control of disease. Radiotherapy concomitant to CDK4/6 inhibitors is feasible and characterized by a fair toxicity profile, with isolated episodes of high-grade reversible intestinal toxicity. Rate of G 3–4 neutropenia was comparable with that measured for CDK4/6 inhibitors alone. Promising results were reported in terms of pain relief and local control of disease.

Aromatase inhibitors (AIs) induce depletion of estrogen levels, causing bone loss and increased fracture risk in women with breast cancer. High‐fat body mass (FBM) emerged as an independent factor associated with the prevalence of morphometric vertebral fractures (VFs) in patients undergoing AIs. We explored the role of lean body mass (LBM) and the interaction of LBM with FBM in predicting the occurrence of VFs in postmenopausal women who were either AI‐naïve or AI‐treated. A total of 684 consecutive breast cancer patients were enrolled in this cross‐sectional study. Each woman underwent a dual‐energy X‐ray absorptiometry (DXA) scan, measuring bone mineral density (BMD), LBM, and FBM; VFs were assessed using a quantitative morphometric analysis of DXA images. After propensity score matching, the study population was restricted to 480 women, 240 AI‐naïve and 240 AI‐treated. We used multivariable logistic regression models to explore the associations between baseline characteristics, VF prevalence and the interaction between LBM, FBM and AI therapy. No interaction between LBM and AI therapy on VF prevalence was shown. Conversely, we reported a significant interaction between LBM, FBM and AI therapy (p = .0311). Among AI‐treated women having LBM below and FBM above or equal the median value, VF prevalence was numerically higher (15/31; 48.4%) than in other subgroups (VF prevalence: 35.7% in high‐LBM and low‐FBM group, 23.2% in high‐LBM and high‐FBM group, and 19.8% in low‐LBM and low‐FBM group). Among AI‐naïve women, the greatest VF proportion was observed in the subgroup with LBM and FBM below median value (25/92; 27.2%). This study suggests a synergism between LBM and FBM in predicting the morphometric VF in women with early breast cancer undergoing AIs. This observation is new and deserves further investigation. The assessment of body composition by DXA might be useful when estimating fracture risk in this population. © 2020 American Society for Bone and Mineral Research © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Background: W taxanes (T) are commonly used in the treatment of older BC pts, with neurotoxicity (NTX) and fatigue being dose-limiting toxicities with a possible negative impact on function. No prospective data exists on the safety and efficacy of W NP in this population. NP might be of particular value in older pts, due to no need for premedication with steroids and shorter time to recovery from neurotoxicity than conventional T, resulting in a reduced risk of exacerbation of comorbidities such as hypertension and diabetes, and possibly of functional decline (FD). Methods: Pts aged ≥ 65 years (y) with Her-2 negative or Her-2 positive (+), but contraindicated to anti-Her-2 therapy, advanced BC were randomized to receive NP as first-line chemotherapy at either 100 (Arm A) or 125 mg/m2 (Arm B), days 1, 8, 15 q 28. The primary end-point was event-free survival (EFS). An event was either disease progression (PD), death, or FD - defined as a decrease of at least 1 point from baseline values of activities of daily living (ADL) or instrumental ADL (IADL), deemed by the investigator as treatment-related and confirmed at the subsequent cycle. Secondary endpoints included progression-free survival (PFS), response rate (RR) in pts with measurable disease, and incidence of adverse events (AEs). Results: From January 2013 to September 2016, 160 pts were randomized in 15 Italian centres; all but 2 who never started NP were eligible for final analysis. Pts median age was 72y (range 65-84) in Arm A and 73y (range 65-88) in Arm B. Median ECOG performance status was 0 (range 0-2). Baseline IADL impairment was reported in 20 pts (25%) in both arms. >80% pts had ER+ tumors; 2 pts had HER2+ disease. Visceral disease was present in 71% (Arm A) and 70% (Arm B) of pts. Prior exposure to T in the neo/adjuvant setting was 14% (Arm A) and 13% (Arm B). Median number of delivered cycles of NP was 6 (range 1-28 in Arm A, and 1-22 in Arm B), with 3 pts still on treatment. Dose reductions were similarly reported (72% of pts Arm A, 78% of pts Arm B). At a median follow-up of 21 months (mos) (Interquartile range 14-28.4) 140 events were observed. Arm A/Arm B: PD n=53(67%)/n=52(66%); FD n=13(15%)/n=14(18%), death n=3(4%)n=5(6%). Outcomes data are reported in the following table: Outcomes Arm AArm BMedian EFS, mos (90% CI)6.2 (5.5-8.4)6.4 (5.8-7.7)Median PFS, mos (95% CI)8.3 (5.9-10.5)8.8 (7.4-10.3)RR (95% CI)37% (25-50)42% (30-54) Fatigue (Arm A: grade (G)2 29%, G3 11%; Arm B: G2 46%, G3 5%) and NTX (Arm A: G2 15%, G3 4%; Arm B: G2 28%, G3 8%) were the most frequently reported AEs. No G4 AEs were reported with the exception of neutropenia (1 pt in arm A) and leucopenia (3 pts in Arm A, 1 pt in arm B). 1 G5 (sepsis) was recorded in Arm B. NTX was reported as the reason for treatment discontinuation in 21 pts (13%) of whom 16 (21%) in arm B. Conclusion: Looking at classical study endpoints (PFS, RR), both doses of NP are active in older pts. However, 17% of pts had to stop treatment due to FD, assessed according to predefined criteria. Due to similar efficacy and reduced NTX, W NP 100 is the suggested dose to be used in older pts with advanced BC. Citation Format: Biganzoli L, Berardi R, Pedersini R, Minisini AM, Caremoli ER, Spazzapan S, Lima JS, Baldari D, Orlando L, Magnolfi E, Pistelli M, Brunello A, Zafarana E, Bernardo A, Leo S, Colleoni M, Donati S, De Placido S, Parolin V, Vitale S, Di Leo A, Puglisi F, Boni L, Cinieri S. The effect trial: A randomized phase II trial evaluating two different doses of weekly (W) NAB-paclitaxel (NP) as first-line chemotherapy in older breast cancer (BC) patients (pts) [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 P6-14-01.

Background: Alopecia is a common and distressing adverse effect in breast cancer (BC) patients (pts) receiving adjuvant chemotherapy. The aim of the study was to assess the effectiveness and safety of this device to prevent chemotherapy-induced alopecia in early breast cancer patients (EBCP) receiving adjuvant treatment. The quality of life of pts was also evaluated. Patients and methods: From January to December 2016, a sensor-controlled scalp cooling system (DigniCap:Sysmex Europe GmbH, Norderstedt, Germany) was proposed to a consecutive group of EBCP submitted to adjuvant chemotherapy at the Breast Unit of Spedali Civili Hospital of Brescia. Degree of hair loss was assessed by two nurse using Dean's alopecia scale by digital photographs at baseline and each chemotherapy cycle. EORTC QLQ-C30 questionnaire and self-reported visual analogical scale (VAS) of symptoms (anxiety, tone of mood, fatigue, nausea,well-being, activity) were collected at baseline and after the first two cycles of chemotherapy. Results: 70 pts were enrolled and 49 (70%) completed the chemotherapy plan and were evaluable. Median age was 51 years, 8 pts (16%) received neoadjuvant and 41 pts (84%) adjuvant chemotherapy, 21 (43%) were treated with 4 cycle of chemotherapy (TC, EC or paclitaxel alone), and 28 (57%) with sequential chemotherapy with antracycline and taxane +- trastuzumab. Fifteen pts (30%) stopped the treatment because of loss of hair in 9 pts, for headache in 4 pts and for other problems in 2 pts. At the end of chemotherapy, 13 pts (27%) had no loss of hair (Dean score 0), 25 pts (51%) had a minimal loss of hair (Dean score 1), 9 pts (18%) had a 50% hair loss (Dean score 2), 2 pts (4%) had a 75% hair loss (Dean score 3). No pts reported hair loss more than 75% (Dean score 4). There wasn't a significant difference between mean score value of QLQ-C30 at baseline and after chemotherapy and between the groups with and without hair loss. VAS documented an increase of fatigue and decrease of anxiety from baseline to final evaluation. The side effects presented with the use of DigniCap were the following: headache in 32% of pts and cold feeling in 57 % of pts. Conclusion: Scalp cooling with cold caps appears to be effective in preventing CIA among the majority of women undergoing treatment chemotherapy. The quality of life did not change in scalp-cooled patients. Acknowledgments: a thank you to the ESA association that donated Dignicap to Oncology Department. Citation Format: Vassalli L, Pedersini R, Romelli M, Claps M, Fornaro C, Conti E, Tagliani M, Baronchelli A, Ragni D, Lombardi E, Rodella F, Amoroso V, Berruti A, Simoncini EL. Efficacy and patient acceptability of the DigniCaP ScalpCooler to prevent hair loss in breast cancer patients receiving adjuvant chemotherapy [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 P6-11-19.

Background: Dysgeusia is a frequent side effect in breast cancer patients undergoing adjuvant chemotherapy. The effect of dysgeusia on changes in diet and patient weight has been poorly investigated. We evaluated prospectively dysgeusia in a consecutive series of early breast cancer patients (EBCP) with the aim to explore its impact on food selection and weight changes. Patients and methods: From May 2014 to April 2017, 130 consecutive EBCP were enrolled at the Oncology and Breast Units at Spedali Civili in Brescia. Dysgeusia was categorized as present or absent, changes in types and frequencies of food consumptions during chemotherapy were assessed by a specific questionnaire and photography atlas. Evaluations were performed at baseline, after 3 cycles, at the end of chemotherapy plan and during follow-up. Results: all 130 pts were evaluable. Median age was 53 years (range 26-76), median weight 64 Kg (range 45-115), median BMI 23,86 Kg/m2 (range 17,01-35,49), 73 pts (56%) performed physical activity, 57 pts (44%) were abstemious, 22 pts (17%) received neoadjuvant and 108 pts (83%) adjuvant chemotherapy, 25 pts (19%) were treated with antracycline based schemes, 83 (64%) with antracycline and taxane plus or minus trastuzumab, and 22 pts (17%) other regimens. Seventy-three per cent of pts developed dysgeusia during chemotherapy (p=< 0.001), and in 19% this side effect persisted three months after chemotherapy. Dysgeusia was associated with the length of chemotherapy treatment and taxane use. A statistically significant increase of taste alteration was reported for all metallic, sweet, bitter, salted and acid taste (p Conclusion: Dysgeusia was frequent in EBCP undergoing adjuvant chemotherapy. It directly correlated with fatigue and meteorism and inversely correlated with mucositis. This adverse event had no impact on weight and BMI but significantly influenced food intake with a preference of glucose containing instead of fat containing foods. Acknowledgments: a thank you to Beretta foundation for the costant support to Breast Unit and Oncology Department. Citation Format: Pedersini R, Zanini A, Romelli M, Coccoli V, Guerra M, Bosio S, Schivardi G, Rodella F, Vassalli L, Amoroso V, Claps M, Simoncini EL, Berruti A. Dysgeusia, weight and eating habits changes in breast cancer patients undergoing chemotherapy: A prospective cohort study [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 P6-11-16.

Nab-P is widely used in MBC, but limited data from clinical practice are available. This is an open-label, multicentre prospective cohort study prospectively collecting data of MBC pts treated with weekly, or every 3 week administration of Nab-P. For this survey a convenience sample was used. An attempt was made to get at least a sample of 200 pts, which guarantees a standard error of 3.5% for estimation of survival time at 1 year, overall response rate and grade 3-4 toxicity. Overall response rate was 32.1% in the whole population, without any significant difference according to schedule, previous paclitaxel exposure, presence of visceral metastases or line of treatment. Median time to progression was 6 months (95% confidence interval, 1-34), with no differences according to the schedule of treatment. No new data on toxicity were reported. Results from this real life experience suggest that Nab-P can be safely used with both the weekly and the 3-weekly schedule with comparable efficacy, leaving the choice to the physician according to the patient's needs and preference, with a carefully balance between activity and potential toxicity. Background Few data are available regarding efficacy and safety of nanoparticle albumin-bound (nab)-paclitaxel in advanced breast cancer patients outside a controlled trial, especially for the weekly schedule. Patients and Methods We prospectively collected data of advanced breast cancer patients who were candidates to be treated with weekly (125 mg/m2 for 3 consecutive weeks followed by a 1-week rest) or every 3 weeks (260 mg/m2) schedules of nab-paclitaxel, according to physician's decision. Results The study enrolled 209 patients, of whom 92 (39.3%) received weekly nab-paclitaxel. The median age was 58 (range, 31-84) years; 21.8% of the patients were classified as triple-negative breast cancer (estrogen-recetor/progesteron-receptor-negative). The median number of cycles was 5.5. The overall response rate was 32.1% in the whole population, without any significant difference according to schedule, previous paclitaxel exposure, presence of visceral metastases, or line of treatment. The median time to disease progression was 6 months (95% confidence interval, 1-34), with no differences according to the schedule of treatment. Severe adverse events (Grade 3-4) were observed in 60.6% of the patients. The main toxicities were alopecia (53.4%), neutropenia (3%), and sensory neuropathy (2.1%). Conclusion Our real-life data indicate that both schedules of nab-paclitaxel are manageable and safe in advanced breast cancer patients, even if previously treated with other taxanes.

INTRODUCTION Second line treatment of recurrent or progressive glioblastoma multiforme (GBM) is not standardized. Anti-angiogenic strategies with tyrosine-kinase inhibitors have been tested with conflicting results. We tested the association of sunitinib plus irinotecan (CPT-11) in a phase II trial in terms of response rate (RR) and 6-months progression-free survival (6-PFS). We also reviewed the clinical evidence from all the trials with sunitinib in this setting published to date and summarized it in a meta-analysis. EVIDENCE ACQUISITION Patients with GBM recurrent or progressive after surgery and standard chemo-radiotherapy were treated with sunitinib 37.5 mg/day for 14 days + CPT-11 125 mg/sqm every 14 days in a Simon's two-stage phase II study. A summary data meta-analysis was performed to establish the 6-PFS in patients with ascertained histological diagnosis of GBM treated with sunitinib. EVIDENCE SYNTHESIS Six patients were enrolled in the stage I of the trial and only one had a stable disease. The overall response rate was 17% and 6-PFS was not reached. Therefore, the trial was stopped early for insufficient activity. All toxicities were grade 1-2. Systematic review of the literature identified 9 studies (including the present one) for a total of 221 patients. Pooled 6-PFS was 15.1% (95% CI: 9.0-24.4). Subgroup analysis by different schedule revealed a 6-PFS of 17.5% (95% CI: 10.3-28.1) in the weekly setting which was consistent across all the studies (I2=0%, P=0.66) and a pooled 6-PFS of 12.7% (95% CI: 4.9-29.1) in the daily setting with a substantial amount of heterogeneity (I2=65%, P=0.01). CONCLUSIONS Results of this trial and those of the systematic review indicate that, compared to conventional chemotherapy or bevacizumab, sunitinib has insufficient activity in the setting of recurrent GBM. Better patient's molecular stratification for second-line treatment in GBM is warranted.

Several trials have demonstrated the benefit of anti-CDK4/6 inhibitors plus endocrine therapy in estrogen receptor-positive (ER+) advanced breast cancer (BC), in first or subsequent lines of therapy. However, due to the lack of direct/indirect comparisons, there are no data demonstrating the superiority of one drug over the other. We compared the effectiveness of palbociclib, ribociclib, and abemaciclib in advanced ER + BC via an indirect adjusted analysis. We performed electronic searches in the PubMed, EMBASE, and Cochrane databases for prospective phase 3 randomized trials evaluating anti-CDK4/6 inhibitors plus endocrine agents. We compared the results with an adjusted indirect analysis of randomized-controlled trials. Outcomes of interest were progression-free survival (PFS), overall response rate (ORR) and G3–4 toxicities occurring in ≥ 5% of patients. Six trials and six treatment arms including a total of 3743 participants, were included. For PFS and ORR analysis, the three agents were similar in both first- and second-line studies. All G3–4 toxicities were similar, with reduced risk of diarrhea for palbociclib versus abemaciclib (relative risk [RR] 0.13, 95% CI 0.02–0.92; P = 0.04) and of QTc prolongation for palbociclib versus ribociclib (RR 0.02, 95% CI 0–0.83; P = 0.03). Despite different inclusion criteria and length of follow-up, similar features were noticed among second-line studies with the exception of increased risk of anemia G3–4 and diarrhea G3–4 for abemaciclib. Based on PFS and ORR results of this indirect meta-analysis, palbociclib, ribociclib, and abemaciclib are equally effective in either first- or second-line therapy for advanced ER + BC. They, however, ported different toxicity profiles.