12 results on '"Sonke G."'
Search Results
2. Additional file 2 of BluePrint molecular subtypes predict response to neoadjuvant pertuzumab in HER2-positive breast cancer
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Liefaard, M. C., van der Voort, A., van Ramshorst, M. S., Sanders, J., Vonk, S., Horlings, H. M., Siesling, S., de Munck, L., van Leeuwen, A. E., Kleijn, M., Mittempergher, L., Kuilman, M. M., Glas, A. M., Wesseling, J., Lips, E. H., and Sonke, G. S.
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Additional file 2. Supplementary Tables.
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- 2023
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3. Effect of physical exercise on cognitive function after chemotherapy in patients with breast cancer: a randomized controlled trial (PAM study)
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Koevoets, E. W., Schagen, S. B., de Ruiter, M. B., Geerlings, M. I., Witlox, L., van der Wall, E., Stuiver, M. M., Sonke, G. S., Velthuis, M. J., Jobsen, J. J., Menke-Pluijmers, M. B. E., Göker, E., van der Pol, C. C., Bos, M. E. M. M., Tick, L. W., van Holsteijn, N. A., van der Palen, J., May, A. M., Monninkhof, E. M., Haringhuizen, Annebeth W., van der Steeg, Wim A., Sommeijer, Dirkje W., Terheggen, Frederiek, Blanken-Peeters, Charlotte, Fliervoet, Harold, Schlooz-Vries, Margrethe S., Frakking, Tanja G., van Tilburg, Marc W. A., Oldenhuis, Corina, Sier, Maartje F., VU University medical center, APH - Quality of Care, APH - Health Behaviors & Chronic Diseases, Medical Oncology, Cognition, Data and Education, Psychology Other Research (FMG), Radiology and Nuclear Medicine, General practice, Master Evidence Based Practice, CCA - Cancer Treatment and Quality of Life, Oncology, APH - Personalized Medicine, and APH - Aging & Later Life
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Strength exercise ,Cognitive complaints ,Physical exercise ,Breast Neoplasms ,Physical fitness ,Oxygen ,Exercise training ,Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10] ,Oxygen Consumption ,Treatment Outcome ,Breast cancer ,Cognition ,SDG 3 - Good Health and Well-being ,Quality of Life ,Humans ,Female ,Exercise ,Fatigue ,Aerobic exercise ,Cancer-related cognitive impairment - Abstract
Background Up to 60% of breast cancer patients treated with chemotherapy is confronted with cognitive problems, which can have a significant impact on daily activities and quality of life (QoL). We investigated whether exercise training improves cognition in chemotherapy-exposed breast cancer patients 2–4 years after diagnosis. Methods Chemotherapy-exposed breast cancer patients, with both self-reported cognitive problems and lower than expected performance on neuropsychological tests, were randomized to an exercise or control group. The 6-month exercise intervention consisted of supervised aerobic and strength training (2 h/week), and Nordic/power walking (2 h/week). Our primary outcome was memory functioning (Hopkins Verbal Learning Test-Revised; HVLT-R). Secondary outcomes included online neuropsychological tests (Amsterdam Cognition Scan; ACS), self-reported cognition (MD Anderson Symptom Inventory for multiple myeloma; MDASI-MM), physical fitness (relative maximum oxygen uptake; VO2peak), fatigue (Multidimensional Fatigue Inventory), QoL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; EORTC QLQ C-30), depression (Patient Health Questionnaire-9, Hospital Anxiety and Depression Scale; HADS), and anxiety (HADS). HVLT-R total recall was analyzed with a Fisher exact test for clinically relevant improvement (≥ 5 words). Other outcomes were analyzed using multiple regression analyses adjusted for baseline and stratification factors. Results We randomized 181 patients to the exercise (n = 91) or control group (n = 90). Two-third of the patients attended ≥ 80% of the exercise sessions, and physical fitness significantly improved compared to control patients (B VO2peak 1.4 ml/min/kg, 95%CI:0.6;2.2). No difference in favor of the intervention group was seen on the primary outcome. Significant beneficial intervention effects were found for self-reported cognitive functioning [MDASI-MM severity (B-0.7, 95% CI − 1.2; − 0.1)], fatigue, QoL, and depression. A hypothesis-driven analysis in highly fatigued patients showed positive exercise effects on tested cognitive functioning [ACS Reaction Time (B-26.8, 95% CI − 52.9; − 0.6) and ACS Wordlist Learning (B4.4, 95% CI 0.5; 8.3)]. Conclusions A 6-month exercise intervention improved self-reported cognitive functioning, physical fitness, fatigue, QoL, and depression in chemotherapy-exposed breast cancer patients with cognitive problems. Tested cognitive functioning was not affected. However, subgroup analysis indicated a positive effect of exercise on tested cognitive functioning in highly fatigued patients. Trial Registration Netherlands Trial Registry: Trial NL5924 (NTR6104). Registered 24 October 2016, https://www.trialregister.nl/trial/5924.
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- 2022
4. Additional file 1 of Effect of physical exercise on cognitive function after chemotherapy in patients with breast cancer: a randomized controlled trial (PAM study)
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Koevoets, E. W., Schagen, S. B., de Ruiter, M. B., Geerlings, M. I., Witlox, L., van der Wall, E., Stuiver, M. M., Sonke, G. S., Velthuis, M. J., Jobsen, J. J., Menke-Pluijmers, M. B. E., Göker, E., van der Pol, C. C., Bos, M. E. M. M., Tick, L. W., van Holsteijn, N. A., van der Palen, J., May, A. M., and Monninkhof, E. M.
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Additional file 1. Table S1. Intervention effects on cognitive functioning. Table S2. Intervention effects on cognitive functioning, per protocol. Table S3. Intervention effects, separately for patients with and without endocrine therapy. Table S4. Intervention effects, separately for patients of different age categories (30-44, 45-59, 60-75 years). Table S5. Intervention effects, separately for patients of with pre- and peri- menopausal status and patients with postmenopausal status. Table S6. Intervention effects on cognitive functioning, stratified for low versus high levels of fatigue measured with the EORTC QLQ C-30 fatigue scale. Table S7. Intervention effects on patient-reported outcomes.
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- 2022
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5. Effect of physical exercise on the hippocampus and global grey matter volume in breast cancer patients: A randomized controlled trial (PAM study)
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Koevoets, E. W., Geerlings, M. I., Monninkhof, E. M., Mandl, R., Witlox, L., van der Wall, E., Stuiver, M. M., Sonke, G. S., Velthuis, M. J., Jobsen, J. J., van der Palen, J., Bos, M. E. M. M., Göker, E., Menke-Pluijmers, M. B. E., Sommeijer, D. W., May, A. M., Haringhuizen, Annebeth W., van der Steeg, Wim A., Terheggen, Frederiek, Blanken-Peeters, Charlotte, Fliervoet, Harold, Schlooz-Vries, Margrethe S., Frakking, Tanja G., van Tilburg, Marc W. A., Oldenhuis, Corina, Sier, Maartje F., van der Pol, Carmen C., Tick, Lidwine W., van Holsteijn, Nel A., de Ruiter, M. B., Schagen, S. B., Psychology Other Research (FMG), Medical Oncology, General practice, Master Evidence Based Practice, CCA - Cancer Treatment and Quality of Life, APH - Quality of Care, APH - Health Behaviors & Chronic Diseases, Oncology, Radiology and Nuclear Medicine, and Rehabilitation medicine
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Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10] ,All institutes and research themes of the Radboud University Medical Center ,Breast cancer ,SDG 3 - Good Health and Well-being ,Neurology ,Cognitive Neuroscience ,Radiology, Nuclear Medicine and imaging ,Neurology (clinical) ,Grey matter volume ,Exercise ,Hippocampus ,Fatigue ,Cortical thickness - Abstract
Contains fulltext : 291410.pdf (Publisher’s version ) (Open Access) BACKGROUND: Physical exercise in cancer patients is a promising intervention to improve cognition and increase brain volume, including hippocampal volume. We investigated whether a 6-month exercise intervention primarily impacts total hippocampal volume and additionally hippocampal subfield volumes, cortical thickness and grey matter volume in previously physically inactive breast cancer patients. Furthermore, we evaluated associations with verbal memory. METHODS: Chemotherapy-exposed breast cancer patients (stage I-III, 2-4 years post diagnosis) with cognitive problems were included and randomized in an exercise intervention (n = 70, age = 52.5 ± 9.0 years) or control group (n = 72, age = 53.2 ± 8.6 years). The intervention consisted of 2x1 hours/week of supervised aerobic and strength training and 2x1 hours/week Nordic or power walking. At baseline and at 6-month follow-up, volumetric brain measures were derived from 3D T1-weighted 3T magnetic resonance imaging scans, including hippocampal (subfield) volume (FreeSurfer), cortical thickness (CAT12), and grey matter volume (voxel-based morphometry CAT12). Physical fitness was measured with a cardiopulmonary exercise test. Memory functioning was measured with the Hopkins Verbal Learning Test-Revised (HVLT-R total recall) and Wordlist Learning of an online cognitive test battery, the Amsterdam Cognition Scan (ACS Wordlist Learning). An explorative analysis was conducted in highly fatigued patients (score of ≥ 39 on the symptom scale 'fatigue' of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire), as previous research in this dataset has shown that the intervention improved cognition only in these patients. RESULTS: Multiple regression analyses and voxel-based morphometry revealed no significant intervention effects on brain volume, although at baseline increased physical fitness was significantly related to larger brain volume (e.g., total hippocampal volume: R = 0.32, B = 21.7 mm(3), 95 % CI = 3.0 - 40.4). Subgroup analyses showed an intervention effect in highly fatigued patients. Unexpectedly, these patients had significant reductions in hippocampal volume, compared to the control group (e.g., total hippocampal volume: B = -52.3 mm(3), 95 % CI = -100.3 - -4.4)), which was related to improved memory functioning (HVLT-R total recall: B = -0.022, 95 % CI = -0.039 - -0.005; ACS Wordlist Learning: B = -0.039, 95 % CI = -0.062 - -0.015). CONCLUSIONS: No exercise intervention effects were found on hippocampal volume, hippocampal subfield volumes, cortical thickness or grey matter volume for the entire intervention group. Contrary to what we expected, in highly fatigued patients a reduction in hippocampal volume was found after the intervention, which was related to improved memory functioning. These results suggest that physical fitness may benefit cognition in specific groups and stress the importance of further research into the biological basis of this finding.
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- 2023
6. Study protocols of three parallel phase 1 trials combining radical radiotherapy with the PARP inhibitor olaparib
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de Haan, R, van Werkhoven, E, van den Heuvel, M M, Peulen, H M U, Sonke, G S, Elkhuizen, P, van den Brekel, M W M, Tesselaar, M E T, Vens, C, Schellens, J H M, van Triest, B, Verheij, M, Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Arbeids- en Organisatie Psychologie (Psychologie, FMG), FMG, MKA AMC (OII, ACTA), Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, CCA - Cancer Treatment and quality of life, Academic Medical Center, and Maxillofacial Surgery (AMC)
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0301 basic medicine ,Oncology ,Cancer Research ,Lung Neoplasms ,medicine.medical_treatment ,Piperazines ,Study Protocol ,chemistry.chemical_compound ,Olaparib ,0302 clinical medicine ,TITE-CRM ,Surgical oncology ,Carcinoma, Non-Small-Cell Lung ,Neoplasms ,Doselimiting toxicity ,Dose limiting toxicity ,Common Terminology Criteria for Adverse Events ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Tolerability ,Head and Neck Neoplasms ,030220 oncology & carcinogenesis ,PARP inhibitor ,Carcinoma, Squamous Cell ,Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] ,medicine.medical_specialty ,Maximum Tolerated Dose ,Antineoplastic Agents ,Breast Neoplasms ,Phase 1 ,Poly(ADP-ribose) Polymerase Inhibitors ,Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9] ,lcsh:RC254-282 ,03 medical and health sciences ,Breast cancer ,SDG 3 - Good Health and Well-being ,Internal medicine ,Genetics ,medicine ,Humans ,Radiotherapy ,Dose escalation ,business.industry ,Radiosensitisation ,medicine.disease ,Head and neck squamous-cell carcinoma ,Radiation therapy ,030104 developmental biology ,chemistry ,Phthalazines ,Radiotherapy, Adjuvant ,business - Abstract
BackgroundPoly (ADP-ribose) Polymerase (PARP) inhibitors are promising novel radiosensitisers. Pre-clinical models have demonstrated potent and tumour-specific radiosensitisation by PARP inhibitors. Olaparib is a PARP inhibitor with a favourable safety profile in comparison to clinically used radiosensitisers including cisplatin when used as single agent. However, data on safety, tolerability and efficacy of olaparib in combination with radiotherapy are limited.MethodsOlaparib is dose escalated in combination with radical (chemo-)radiotherapy regimens for non-small cell lung cancer (NSCLC), breast cancer and head and neck squamous cell carcinoma (HNSCC) in three parallel single institution phase 1 trials. All trials investigate a combination treatment of olaparib and radiotherapy, the NSCLC trial also investigates a triple combination of olaparib, radiotherapy and concurrent low dose cisplatin. The primary objective is to identify the maximum tolerated dose of olaparib in these combination treatments, defined as the dose closest to but not exceeding a 15% probability of dose limiting toxicity. Each trial has a separate dose limiting toxicity definition, taking into account incidence, duration and severity of expected toxicities without olaparib. Dose escalation is performed using a time-to-event continual reassessment method (TITE-CRM). TITE-CRM enables the incorporation of late onset toxicity until one year after treatment in the dose limiting toxicity definition while maintaining an acceptable trial duration. Olaparib treatment starts two days before radiotherapy and continues during weekends until two days after radiotherapy. Olaparib will also be given two weeks and one week before radiotherapy in the breast cancer trial and HNSCC trial respectively to allow for translational research. Toxicity is scored using common terminology criteria for adverse events (CTCAE) version 4.03. Blood samples, and tumour biopsies in the breast cancer trial, are collected for pharmacokinetic and pharmacodynamic analyses.DiscussionWe designed three parallel phase 1 trials to assess the safety and tolerability of the PARP inhibitor olaparib in combination with radical (chemo-)radiotherapy treatment regimens. PARP inhibitors have the potential to improve outcomes in patients treated with radical (chemo-)radiotherapy, by achieving higher locoregional control rates and/or less treatment associated toxicity.Trial registrationClinicalTrials.govIdentifiers: NCT01562210 (registered March 23, 2012), NCT02227082 (retrospectively registered August 27, 2014), NCT02229656 (registered September 1, 2014).
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- 2019
7. Overall Survival With Maintenance Olaparib at a 7-Year Follow-up in Patients With Newly Diagnosed Advanced Ovarian Cancer and a BRCA Mutation: The SOLO1/GOG 3004 Trial
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Paul DiSilvestro, Susana Banerjee, Nicoletta Colombo, Giovanni Scambia, Byoung-Gie Kim, Ana Oaknin, Michael Friedlander, Alla Lisyanskaya, Anne Floquet, Alexandra Leary, Gabe S. Sonke, Charlie Gourley, Amit Oza, Antonio González-Martín, Carol Aghajanian, William Bradley, Cara Mathews, Joyce Liu, John McNamara, Elizabeth S. Lowe, Mei-Lin Ah-See, Kathleen N. Moore, Institut Català de la Salut, [DiSilvestro P] Program in Women's Oncology, Women & Infants Hospital, Providence, RI. [Banerjee S] The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, United Kingdom. [Colombo N] University of Milan-Bicocca and Istituto Europeo di Oncologia IRCCS, Milan, Italy. [Scambia G] Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. [Kim BG] Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. [Oaknin A] Gynaecologic Cancer Programme, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d'Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Disilvestro, P, Banerjee, S, Colombo, N, Scambia, G, Kim, B, Oaknin, A, Friedlander, M, Lisyanskaya, A, Floquet, A, Leary, A, Sonke, G, Gourley, C, Oza, A, González-Martín, A, Aghajanian, C, Bradley, W, Mathews, C, Liu, J, Mcnamara, J, Lowe, E, Ah-See, M, and Moore, K
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Cancer Research ,Otros calificadores::/uso terapéutico [Otros calificadores] ,Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms [DISEASES] ,Genetic Phenomena::Genetic Variation::Mutation [PHENOMENA AND PROCESSES] ,Medicaments antineoplàstics - Ús terapèutic ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos [COMPUESTOS QUÍMICOS Y DROGAS] ,Obstetrics and Gynecology ,General Medicine ,Ovaris - Càncer - Tractament ,neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas [ENFERMEDADES] ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,Ovarian Cancer ,Olaparib ,Settore MED/40 - GINECOLOGIA E OSTETRICIA ,Anomalies cromosòmiques ,Oncology ,SOLO1/GOG 3004 Trial ,Other subheadings::/therapeutic use [Other subheadings] ,Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [CHEMICALS AND DRUGS] ,BRCA Mutation ,fenómenos genéticos::variación genética::mutación [FENÓMENOS Y PROCESOS] - Abstract
PURPOSE In SOLO1/GOG 3004 (ClinicalTrials.gov identifier: NCT01844986 ), maintenance therapy with the poly(ADP-ribose) polymerase inhibitor olaparib provided a sustained progression-free survival benefit in patients with newly diagnosed advanced ovarian cancer and a BRCA1 and/or BRCA2 (BRCA) mutation. We report overall survival (OS) after a 7-year follow-up, a clinically relevant time point and the longest follow-up for any poly(ADP-ribose) polymerase inhibitor in the first-line setting. METHODS This double-blind phase III trial randomly assigned patients with newly diagnosed advanced ovarian cancer and a BRCA mutation in clinical response to platinum-based chemotherapy to maintenance olaparib (n = 260) or placebo (n = 131) for up to 2 years. A prespecified descriptive analysis of OS, a secondary end point, was conducted after a 7-year follow-up. RESULTS The median duration of treatment was 24.6 months with olaparib and 13.9 months with placebo, and the median follow-up was 88.9 and 87.4 months, respectively. The hazard ratio for OS was 0.55 (95% CI, 0.40 to 0.76; P = .0004 [ P < .0001 required to declare statistical significance]). At 7 years, 67.0% of olaparib patients versus 46.5% of placebo patients were alive, and 45.3% versus 20.6%, respectively, were alive and had not received a first subsequent treatment (Kaplan-Meier estimates). The incidence of myelodysplastic syndrome and acute myeloid leukemia remained low, and new primary malignancies remained balanced between treatment groups. CONCLUSION Results indicate a clinically meaningful, albeit not statistically significant according to prespecified criteria, improvement in OS with maintenance olaparib in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation and support the use of maintenance olaparib to achieve long-term remission in this setting; the potential for cure may also be enhanced. No new safety signals were observed during long-term follow-up.
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- 2023
8. Efficacy and safety of olaparib according to age in BRCA1/2-mutated patients with recurrent platinum-sensitive ovarian cancer: Analysis of the phase III SOLO2/ENGOT-Ov21 study
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Fabian Trillsch, Sven Mahner, Beyhan Ataseven, Rebecca Asher, Nanda Aryal, Coraline Dubot, Andrew Clamp, Richard T. Penson, Amit Oza, Amnon Amit, Tomasz Huzarski, Antonio Casado, Giovanni Scambia, Michael Friedlander, Nicoletta Colombo, Keiichi Fujiwara, Gabe S. Sonke, Hannelore Denys, Elizabeth S. Lowe, Chee K. Lee, Eric Pujade-Lauraine, Trillsch, F, Mahner, S, Ataseven, B, Asher, R, Aryal, N, Dubot, C, Clamp, A, Penson, R, Oza, A, Amit, A, Huzarski, T, Casado, A, Scambia, G, Friedlander, M, Colombo, N, Fujiwara, K, Sonke, G, Denys, H, Lowe, E, Lee, C, and Pujade-Lauraine, E
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Ovarian Neoplasms ,Age dependency ,Quality of life ,BRCA1 Protein ,Obstetrics and Gynecology ,Carcinoma, Ovarian Epithelial ,Piperazines ,Settore MED/40 - GINECOLOGIA E OSTETRICIA ,Olaparib ,PARP inhibitor ,Oncology ,Ovarian cancer ,Child, Preschool ,Mutation ,Humans ,Phthalazines ,Female ,Neoplasm Recurrence, Local ,PARP inhibitors ,Aged - Abstract
Background: Olaparib has significantly improved outcome and patient-centered endpoints in BRCA1/2-mutated patients with recurrent platinum-sensitive ovarian cancer (PSOC). Specific information on efficacy and safety of olaparib for older patients appears of special interest. Methods: 295 patients from the SOLO2 trial randomly assigned to olaparib or placebo were categorized according to age-cutoff at 65 years. Efficacy, tolerability, and quality of life (QoL) of olaparib relative to placebo within in each age group was analyzed. Results: Baseline characteristics were similar in patients ≥65 years (N = 62;21.0%) compared to patients
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- 2022
9. Tolerability of maintenance olaparib in newly diagnosed patients with advanced ovarian cancer and a BRCA mutation in the randomized phase III SOLO1 trial
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Gabe S. Sonke, Cara Mathews, Carol Aghajanian, Nicoletta Colombo, Alexandra Leary, Ana Oaknin, Joyce F. Liu, Giovanni Scambia, William H. Bradley, Elizabeth S. Lowe, Jae Weon Kim, Alla Lisyanskaya, Antonio González-Martín, Anne Floquet, Michael Friedlander, Kathleen N. Moore, Ralph Bloomfield, Amit M. Oza, Charlie Gourley, Susana Banerjee, Paul DiSilvestro, Colombo, N, Moore, K, Scambia, G, Oaknin, A, Friedlander, M, Lisyanskaya, A, Floquet, A, Leary, A, Sonke, G, Gourley, C, Banerjee, S, Oza, A, Gonzalez-Martin, A, Aghajanian, C, Bradley, W, Kim, J, Mathews, C, Liu, J, Lowe, E, Bloomfield, R, Disilvestro, P, Institut Català de la Salut, [Colombo N] University of Milan-Bicocca and IEO European Institute of Oncology IRCCS, Milan, Italy. [Moore K] Stephenson Cancer Center at the University of Oklahoma, Oklahoma City, OK, United States. [Scambia G] Fondazione Policlinico Universitario A. Gemelli IRCCS Università Cattolica, Rome, Italy. [Oaknin A] Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Friedlander M] University of New South Wales Clinical School, Prince of Wales Hospital, Randwick, Australia. [Lisyanskaya A] St Petersburg City Oncology Dispensary, St Petersburg, Russia, and Vall d'Hebron Barcelona Hospital Campus
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medicine.medical_specialty ,Nausea ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas [ENFERMEDADES] ,Neutropenia ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,Piperazines ,Olaparib ,chemistry.chemical_compound ,Double-Blind Method ,Ovarian cancer ,Internal medicine ,Humans ,Medicine ,Adverse effect ,BRCA2 Protein ,Ovarian Neoplasms ,BRCA1 Protein ,business.industry ,Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms [DISEASES] ,BRCA mutation ,Obstetrics and Gynecology ,Ovaris - Càncer - Tractament ,Middle Aged ,Tolerability ,medicine.disease ,Newly diagnosed ,Discontinuation ,Oncology ,chemistry ,Mutation ,Avaluació de resultats (Assistència sanitària) ,Vomiting ,Phthalazines ,Female ,Safety ,medicine.symptom ,business - Abstract
Olaparib; Ovarian cancer; Tolerability Olaparib; Cáncer de ovarios; Tolerabilidad Olaparib; Càncer d'ovaris; Tolerabilitat Objectives In the phase III SOLO1 trial (NCT01844986), maintenance olaparib provided a substantial progression-free survival benefit in patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation who were in response after platinum-based chemotherapy. We analyzed the timing, duration and grade of the most common hematologic and non-hematologic adverse events in SOLO1. Methods Eligible patients were randomized to olaparib tablets 300 mg twice daily (N = 260) or placebo (N = 131), with a 2-year treatment cap in most patients. Safety outcomes were analyzed in detail in randomized patients who received at least one dose of study drug (olaparib, n = 260; placebo, n = 130). Results Median time to first onset of the most common hematologic (anemia, neutropenia, thrombocytopenia) and non-hematologic (nausea, fatigue/asthenia, vomiting) adverse events was
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- 2021
10. Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer
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Alla Lisyanskaya, Giovanni Scambia, Amit M. Oza, Ralph Bloomfield, Cara Mathews, Paul DiSilvestro, Alexandra Leary, Michael Friedlander, Ana Oaknin, Anne Floquet, Nicoletta Colombo, Carol Aghajanian, Susana Banerjee, Kathleen N. Moore, William H. Bradley, Elizabeth S. Lowe, Byoung Gie Kim, Antonio González-Martín, Gabe S. Sonke, Charlie Gourley, Joyce F. Liu, Moore, K, Colombo, N, Scambia, G, Kim, B, Oaknin, A, Friedlander, M, Lisyanskaya, A, Floquet, A, Leary, A, Sonke, G, Gourley, C, Banerjee, S, Oza, A, González-Martín, A, Aghajanian, C, Bradley, W, Mathews, C, Liu, J, Lowe, E, Bloomfield, R, and Disilvestro, P
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0301 basic medicine ,Oncology ,endocrine system diseases ,medicine.medical_treatment ,Genes, BRCA2 ,Genes, BRCA1 ,Phases of clinical research ,Kaplan-Meier Estimate ,Piperazines ,Poly(ADP-ribose) Polymerase Inhibitor ,Antineoplastic Agent ,chemistry.chemical_compound ,0302 clinical medicine ,Peritoneal Neoplasms ,Phthalazine ,Ovarian Neoplasms ,Standard treatment ,Obstetrics and Gynecology ,General Medicine ,Middle Aged ,Combined Modality Therapy ,Progression-Free Survival ,female genital diseases and pregnancy complications ,030220 oncology & carcinogenesis ,Female ,Cytoreductive surgery ,Peritoneal Neoplasm ,Carcinoma, Endometrioid ,Adjuvant ,Human ,Adult ,medicine.medical_specialty ,Antineoplastic Agents ,Newly diagnosed ,Poly(ADP-ribose) Polymerase Inhibitors ,Maintenance Chemotherapy ,Olaparib ,03 medical and health sciences ,Double-Blind Method ,Internal medicine ,Platinum chemotherapy ,medicine ,Carcinoma ,Fallopian Tube Neoplasms ,Humans ,In patient ,Fallopian Tube Neoplasm ,Progression-free survival ,Rucaparib ,Piperazine ,Germ-Line Mutation ,Advanced ovarian cancer ,Chemotherapy ,business.industry ,Ovarian Neoplasm ,medicine.disease ,Clinical trial ,030104 developmental biology ,chemistry ,Phthalazines ,business - Abstract
BACKGROUND: Most women with newly diagnosed advanced ovarian cancer have a relapse within 3 years after standard treatment with surgery and platinum-based chemotherapy. The benefit of the oral poly(adenosine diphosphate–ribose) polymerase inhibitor olaparib in relapsed disease has been well established, but the benefit of olaparib as maintenance therapy in newly diagnosed disease is uncertain.METHODS: We conducted an international, randomized, double-blind, phase 3 trial to evaluate the efficacy of olaparib as maintenance therapy in patients with newly diagnosed advanced (International Federation of Gynecology and Obstetrics stage III or IV) high-grade serous or endometrioid ovarian cancer, primary peritoneal cancer, or fallopian-tube cancer (or a combination thereof) with a mutation in BRCA1, BRCA2, or both (BRCA1/2) who had a complete or partial clinical response after platinum-based chemotherapy. The patients were randomly assigned, in a 2:1 ratio, to receive olaparib tablets (300 mg twice daily) or placebo. The primary end point was progression-free survival.RESULTS: Of the 391 patients who underwent randomization, 260 were assigned to receive olaparib and 131 to receive placebo. A total of 388 patients had a centrally confirmed germline BRCA1/2 mutation, and 2 patients had a centrally confirmed somatic BRCA1/2 mutation. After a median follow-up of 41 months, the risk of disease progression or death was 70% lower with olaparib than with placebo (Kaplan–Meier estimate of the rate of freedom from disease progression and from death at 3 years, 60% vs. 27%; hazard ratio for disease progression or death, 0.30; 95% confidence interval, 0.23 to 0.41; PCONCLUSIONS: The use of maintenance therapy with olaparib provided a substantial benefit with regard to progression-free survival among women with newly diagnosed advanced ovarian cancer and a BRCA1/2 mutation, with a 70% lower risk of disease progression or death with olaparib than with placebo. (Funded by AstraZeneca and Merck; SOLO1 ClinicalTrials.gov number, NCT01844986. opens in new tab.)
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- 2018
11. Phase III Randomized Study of Ribociclib and Fulvestrant in Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer: MONALEESA-3
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Xavier Pivot, Michelle Miller, Seock-Ah Im, Francisco J. Esteva, Yingbo Wang, Miguel Martin, Arnd Nusch, Luis de la Cruz-Merino, Karen Rodriguez Lorenc, Patrick Neven, Dennis J. Slamon, K. Petrakova, Peter A. Fasching, J. Thaddeus Beck, Stephen Chia, Michelino De Laurentiis, Gena Vidam, Guy Jerusalem, Giulia Val Bianchi, Gabe S. Sonke, Tetiana Taran, Slamon, D. J., Neven, P., Chia, S., Fasching, P. A., De Laurentiis, M., Im, S. -A., Petrakova, K., Val Bianchi, G., Esteva, F. J., Martin, M., Nusch, A., Sonke, G. S., De La Cruz-Merino, L., Beck, J. T., Pivot, X., Vidam, G., Wang, Y., Lorenc, K. R., Miller, M., Taran, T., and Jerusalem, G.
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Adult ,0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Receptor, ErbB-2 ,Aminopyridines ,Anastrozole ,Breast Neoplasms ,Kaplan-Meier Estimate ,Palbociclib ,Gene mutation ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Progression-free survival ,Fulvestrant ,Purine ,Aged ,Aged, 80 and over ,Antineoplastic Combined Chemotherapy Protocol ,business.industry ,Goserelin ,Middle Aged ,medicine.disease ,Metastatic breast cancer ,Progression-Free Survival ,Aminopyridine ,030104 developmental biology ,Receptors, Estrogen ,Purines ,030220 oncology & carcinogenesis ,Hormonal therapy ,Female ,Receptors, Progesterone ,business ,Breast Neoplasm ,Human ,medicine.drug - Abstract
Purpose This phase III study evaluated ribociclib plus fulvestrant in patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer who were treatment naïve or had received up to one line of prior endocrine therapy in the advanced setting. Patients and Methods Patients were randomly assigned at a two-to-one ratio to ribociclib plus fulvestrant or placebo plus fulvestrant. The primary end point was locally assessed progression-free survival. Secondary end points included overall survival, overall response rate, and safety. Results A total of 484 postmenopausal women were randomly assigned to ribociclib plus fulvestrant, and 242 were assigned to placebo plus fulvestrant. Median progression-free survival was significantly improved with ribociclib plus fulvestrant versus placebo plus fulvestrant: 20.5 months (95% CI, 18.5 to 23.5 months) versus 12.8 months (95% CI, 10.9 to 16.3 months), respectively (hazard ratio, 0.593; 95% CI, 0.480 to 0.732; P < .001). Consistent treatment effects were observed in patients who were treatment naïve in the advanced setting (hazard ratio, 0.577; 95% CI, 0.415 to 0.802), as well as in patients who had received up to one line of prior endocrine therapy for advanced disease (hazard ratio, 0.565; 95% CI, 0.428 to 0.744). Among patients with measurable disease, the overall response rate was 40.9% for the ribociclib plus fulvestrant arm and 28.7% for placebo plus fulvestrant. Grade 3 adverse events reported in ≥ 10% of patients in either arm (ribociclib plus fulvestrant v placebo plus fulvestrant) were neutropenia (46.6% v 0%) and leukopenia (13.5% v 0%); the only grade 4 event reported in ≥ 5% of patients was neutropenia (6.8% v 0%). Conclusion Ribociclib plus fulvestrant might represent a new first- or second-line treatment option in hormone receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer.
- Published
- 2018
12. Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: a randomised phase 2 trial
- Author
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Barbara Schmalfeldt, Michael Friedlander, Helen Mackay, Gabe S. Sonke, H. Hirte, Jacqui Rowbottom, Christopher J. Poole, Ron H.J. Mathijssen, Amit M. Oza, Brian Dougherty, J. Carl Barrett, Elizabeth S. Lowe, Marie Plante, Nicoletta Colombo, Jiří Špaček, David Cibula, Ana Oaknin Benzaquen, Peter Vuylsteke, Sven Mahner, Oza, A, Cibula, D, Benzaquen, A, Poole, C, Mathijssen, R, Sonke, G, Colombo, N, Špaček, J, Vuylsteke, P, Hirte, H, Mahner, S, Plante, M, Schmalfeldt, B, Mackay, H, Rowbottom, J, Lowe, E, Dougherty, B, Barrett, J, Friedlander, M, and Medical Oncology
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Time Factors ,medicine.medical_treatment ,Phases of clinical research ,Administration, Oral ,Neoplasms, Cystic, Mucinous, and Serou ,Gastroenterology ,Piperazines ,Carboplatin ,Poly(ADP-ribose) Polymerase Inhibitor ,Antineoplastic Agent ,chemistry.chemical_compound ,Antineoplastic Combined Chemotherapy Protocols ,Enzyme Inhibitor ,Molecular Targeted Therapy ,Enzyme Inhibitors ,Poly(ADP-ribose) Polymerase ,Phthalazine ,Ovarian Neoplasms ,BRCA1 Protein ,Medicine (all) ,Middle Aged ,Treatment Outcome ,Tolerability ,Oncology ,Response Evaluation Criteria in Solid Tumors ,Administration, Intravenous ,Female ,Poly(ADP-ribose) Polymerases ,Human ,Adult ,medicine.medical_specialty ,Paclitaxel ,Time Factor ,Antineoplastic Agents ,Administration, Intravenou ,Poly(ADP-ribose) Polymerase Inhibitors ,Disease-Free Survival ,Drug Administration Schedule ,Olaparib ,Young Adult ,SDG 3 - Good Health and Well-being ,Internal medicine ,medicine ,Humans ,Piperazine ,Aged ,BRCA2 Protein ,Chemotherapy ,Antineoplastic Combined Chemotherapy Protocol ,business.industry ,Ovarian Neoplasm ,medicine.disease ,Surgery ,Regimen ,chemistry ,Mutation ,Phthalazines ,Neoplasm Grading ,Neoplasm Recurrence, Local ,Ovarian cancer ,business ,Neoplasms, Cystic, Mucinous, and Serous - Abstract
Summary Background The poly(ADP-ribose) polymerase inhibitor olaparib has shown antitumour activity in patients with platinum-sensitive, recurrent, high-grade serous ovarian cancer with or without BRCA1 or BRCA2 mutations. The aim of this study was to assess the efficacy and tolerability of olaparib in combination with chemotherapy, followed by olaparib maintenance monotherapy, versus chemotherapy alone in patients with platinum-sensitive, recurrent, high-grade serous ovarian cancer. Methods In this randomised, open-label, phase 2 study, adult patients with platinum-sensitive, recurrent, high-grade serous ovarian cancer who had received up to three previous courses of platinum-based chemotherapy and who were progression free for at least 6 months before randomisation received either olaparib (200 mg capsules twice daily, administered orally on days 1–10 of each 21-day cycle) plus paclitaxel (175 mg/m 2 , administered intravenously on day 1) and carboplatin (area under the curve [AUC] 4 mg/mL per min, according to the Calvert formula, administered intravenously on day 1), then olaparib monotherapy (400 mg capsules twice daily, given continuously) until progression (the olaparib plus chemotherapy group), or paclitaxel (175 mg/m 2 on day 1) and carboplatin (AUC 6 mg/mL per min on day 1) then no further treatment (the chemotherapy alone group). Randomisation was done by an interactive voice response system, stratified by number of previous platinum-containing regimens received and time to disease progression after the previous platinum regimen. The primary endpoint was progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1, analysed by intention to treat. Prespecified exploratory analyses included efficacy by BRCA mutation status, assessed retrospectively. This study is registered with ClinicalTrials.gov, number NCT01081951, and has been completed. Findings Between Feb 12 and July 30, 2010, 173 patients at 43 investigational sites in 12 countries were enrolled into the study, of whom 162 were eligible and were randomly assigned to the two treatment groups (81 to the olaparib plus chemotherapy group and 81 to the chemotherapy alone group). Of these randomised patients, 156 were treated in the combination phase (81 in the olaparib plus chemotherapy group and 75 in the chemotherapy alone group) and 121 continued to the maintenance or no further treatment phase (66 in the olaparib plus chemotherapy group and 55 in the chemotherapy alone group). BRCA mutation status was known for 107 patients (either at baseline or determined retrospectively): 41 (38%) of 107 had a BRCA mutation (20 in the olaparib plus chemotherapy group and 21 in the chemotherapy alone group). Progression-free survival was significantly longer in the olaparib plus chemotherapy group (median 12·2 months [95% CI 9·7–15·0]) than in the chemotherapy alone group (median 9·6 months [95% CI 9·1–9·7) (HR 0·51 [95% CI 0·34–0·77]; p=0·0012), especially in patients with BRCA mutations (HR 0·21 [0·08–0·55]; p=0·0015). In the combination phase, adverse events that were reported at least 10% more frequently with olaparib plus chemotherapy than with chemotherapy alone were alopecia (60 [74%] of 81 vs 44 [59%] of 75), nausea (56 [69%] vs 43 [57%]), neutropenia (40 [49%] vs 29 [39%]), diarrhoea (34 [42%] vs 20 [27%]), headache (27 [33%] vs seven [9%]), peripheral neuropathy (25 [31%] vs 14 [19%]), and dyspepsia (21 [26%] vs 9 [12%]); most were of mild-to-moderate intensity. The most common grade 3 or higher adverse events during the combination phase were neutropenia (in 35 [43%] of 81 patients in the olaparib plus chemotherapy group vs 26 [35%] of 75 in the chemotherapy alone group) and anaemia (seven [9%] vs five [7%]). Serious adverse events were reported in 12 (15%) of 81 patients in the olaparib plus chemotherapy group and 16 of 75 (21%) patients in the chemotherapy alone group. Interpretation Olaparib plus paclitaxel and carboplatin followed by maintenance monotherapy significantly improved progression-free survival versus paclitaxel plus carboplatin alone, with the greatest clinical benefit in BRCA -mutated patients, and had an acceptable and manageable tolerability profile. Funding AstraZeneca.
- Published
- 2015
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