The impact of olaparib dose reduction and treatment interruption on treatment outcome in the SOLO2/ENGOT-ov21 platinum-sensitive recurrent ovarian cancer.

Autor:	Francis KE; National Health and Medical Research Council Clinical Trials Centre, The University of Sydney, Sydney, Australia; Department of Medical Oncology, St George Hospital, Kogarah, Australia. Electronic address: katherine.francis@sydney.edu.au., Kim SI; Seoul National University Hospital, Seoul, Korea., Friedlander M; Prince of Wales Clinical School, UNSW, Sydney, Australia; Department of Medical Oncology, Prince of Wales Hospital, Randwick, Australia., Gebski V; National Health and Medical Research Council Clinical Trials Centre, The University of Sydney, Sydney, Australia., Ray-Coquard I; ARCAGY-GINECO, Paris, France; Centre Léon Bérard, Lyon, France., Clamp A; The Christie NHS Foundation Trust and University of Manchester, Manchester, UK., Penson RT; Harvard Medical School, Massachusetts General Hospital, Boston, USA., Oza A; Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada., Perri T; Gynecologic Oncology Department, Sheba Medical Hospital, Tel Aviv, Israel., Huzarski T; Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland; Read-Gene SA, Westpomerania, Grzepnica, Poland., Martin-Lorente C; Hospital Universitario de la Santa Creu i Sant Pau, Barcelona; GEICO, Madrid, Spain., Cecere SC; Department of Uro-Gynecology, Division of Experimental Uro-Gynecological Oncology, National Cancer Institute IRCCS Fondazione 'G. Pascale', Naples, Italy., Colombo N; Università Milano-Bicocca, Istituto Europeo Oncologia, Milan, Italy., Ataseven B; Department of Gynecology and Gynecologic Oncology, Evang. Kliniken Essen-Mitte, Essen, Germany; Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Munich, Germany., Fujiwara K; Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Saitama, Japan., Sonke G; The Dutch Gynecological Oncology Group (DGOG), Utrecht, the Netherlands; Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands., Vergote I; Belgium and Luxembourg Gynaecological Oncology Group (BGOG), Leuven, Belgium; Department of Oncology, KU Leuven - University of Leuven, Leuven, Belgium., Pujade-Lauraine E; ARCAGY-GINECO, Paris, France; Université Paris Descartes, Paris, France., Kim JW; Seoul National University Hospital, Seoul, Korea., Lee CK; National Health and Medical Research Council Clinical Trials Centre, The University of Sydney, Sydney, Australia; Department of Medical Oncology, St George Hospital, Kogarah, Australia.
Jazyk:	angličtina
Zdroj:	Annals of oncology : official journal of the European Society for Medical Oncology [Ann Oncol] 2022 Jun; Vol. 33 (6), pp. 593-601. Date of Electronic Publication: 2022 Feb 24.
DOI:	10.1016/j.annonc.2022.02.222
Abstrakt:	Background: Maintenance treatment with poly (ADP-ribose) polymerase (PARP) inhibitor is now the standard of care in patients with BRCA-mutated platinum-sensitive recurrent ovarian cancer following response to chemotherapy. In the SOLO2 trial, adverse event (AE)-associated olaparib interruption, dose reduction, and discontinuation occurred in 50%, 28%, and 17% of patients, respectively. We used data from the SOLO2 trial to evaluate the impact of dose alterations on survival outcomes and identified baseline characteristics associated with dose alteration. Patients and Methods: We computed relative dose intensity (RDI) defined as the received dose as a percentage of the standard dose (300 mg twice a day) during the first 12 weeks on treatment. Patients were categorized into RDI >98%, RDI 90%-98%, and RDI <90%. The association between RDI categories with progression-free survival (PFS) and overall survival (OS) were examined using a 12-week landmark Cox regression analysis. Logistic regression analysis was used to correlate baseline factors with RDI at 12 weeks. Results: In patients on olaparib included in the landmark analysis (n = 185), the mean 12-week RDI was 91.4%. There was no significant difference across 12-week RDI >98% (n = 110), 90%-98% (n = 29), and <90% (n = 45) categories for PFS (median, 14.2 versus 19.3 versus 34.4 months; P = 0.37) and OS (median, 49.7 versus 49.5 versus 54.1 months; P = 0.84). Risk of RDI ≤90% increased with baseline performance status 1 [odds ratio (OR): 2.54; 95% confidence interval (CI): 1.11-5.82] any nausea (OR: 3.17; 95% CI: 0.9-11.23), and with body weight ≤70 kg (OR: 1.86; 95% CI: 0.92-3.76). Conclusions: Dose reduction and interruption for the management of olaparib-associated AEs during the first 12 weeks did not impact on PFS and OS. When counselling patients requiring dose reductions or interruptions due to AEs, the results of this study will help assure patients that their outcomes will not be adversely affected. Competing Interests: Disclosure KEF reports intuitional funding from AstraZeneca (AZ). MF reports institutional funding from AZ, Novartis, and Beigene; consulting fees from AZ, Novartis, GlaxoSimthKline (GSK), Merck Sharp & Dohme (MSD), Takeda, and Lilly; honoraria for lectures from AZ, GSK, and ACT-Genomics; travel support from AZ; and participation in a data advisory role with Australasian Gastro-Intestinal Cancer Trials Group and Independent Data and Safety Monitoring Board. IRC reports personal fees and travel support from AZ, GSK, and Clovis Oncology; and personal fees from Roche, Mersana, Deciphera, Eisai, Amgen, Bristol Myers Squibb, OncXerna, and Aravive. AC reports institutional research funding from AZ; payment from Clovis Oncology for lectures and travel support; and he participates in an advisory role to AZ. RP reports institutional funding from AZ. He participates in an advisory role to AbbVie, AZ, Care4ward (unpaid), Clovis Oncology, Curio Science, Eisai Inc., Genentech, Janssen Oncology (J&J), Merck & Co., Mersana Therapeutics, Inc., NewLink Genetics, Nexus Global Group, Pieris Pharma Inc., Roche, Inc., Sutro Biopharma, Syndax Pharmaceuticals, Tesaro Inc., Vascular Biogenics Ltd. NC reports grants, consulting fees, and personal fees from AZ; consulting fees and personal fees from GSK; and personal fees from Tesaro, Novartis, Clovis, MSD, GSK, EISAI. She participates in an advisory role with Roche, PharmaMar, AZ, Clovis Oncology, MSD, GSK, Tesaro, Pfizer, BIOCAD, ImmunoGen, Mersana, OncXerna, and Eisai. KF reports institutional research funding and honoraria for lectures from AZ. GS reports institutional research funding from AZ, MSD, Novartis, and Roche; and consulting fees paid to the institution from BioViva and Segen. IV reports receiving institutional fees from Oncoinvent AS and Genmab; grant funding from Amgen and Roche; consulting fees from Aksebio, Amgen, GmbH, AZ, Clovis Oncology, Carrick Therapeutics, Deciphera Pharmaceuticals, Eisai, Elevar Therapeutics, Roche, Genmab, GSK, Immunogen Inc., Jazz Pharma, Karyopharm, Mersana, Millennium Pharmaceuticals, MSD, Novocure, Novartis, Octimet Oncology NV, Oncoinvent AS, Sotio a.s., Verastem Oncology, Zentalis; and travel expenses from Amgen, MSD, Tesaro, AZ, Roche. EPL reports medical writing assistance for the primary SOLO2 publication from AZ; institutional grants from AZ and Merck; personal payments for lectures from AZ and GSK; and participation in an advisory role with Incyte, Roche, and Pfizer. He reports other interests including as an employee of ARCAGY GINECO research group. CKL reports institutional payments from Roche, AZ, and Merck KGA; and personal payments for lectures, presentations or travel support from AZ, Amgen, Takeda, Boehringer Ingelheim, Pfizer, Yuhan, Merck KGA, Roche, and MSD. All other authors have declared no conflicts of interest. (Copyright © 2022 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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