Tolerability of maintenance olaparib in newly diagnosed patients with advanced ovarian cancer and a BRCA mutation in the randomized phase III SOLO1 trial.

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. 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). Median time to first onset of the most common hematologic (anemia, neutropenia, thrombocytopenia) and non-hematologic (nausea, fatigue/asthenia, vomiting) adverse events was <3 months in olaparib-treated patients. The first event of anemia, neutropenia, thrombocytopenia, nausea and vomiting lasted a median of <2 months and the first event of fatigue/asthenia lasted a median of 3.48 months in the olaparib group. These adverse events were manageable with supportive treatment and/or olaparib dose modification in most patients, with few patients requiring discontinuation of olaparib. Of 162 patients still receiving olaparib at month 24, 64.2% were receiving the recommended starting dose of olaparib 300 mg twice daily. Maintenance olaparib had a predictable and manageable adverse event profile in the newly diagnosed setting with no new safety signals identified. Adverse events usually occurred early, were largely manageable and led to discontinuation in a minority of patients.

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Déclaration de conflit d'intérêts

Declaration of competing interest NC reports personal fees from AstraZeneca during the conduct of the study; and personal fees from MSD, Roche, Tesaro, GSK, Clovis Oncology, PharmaMar, Pfizer, Amgen, Novartis, Biocad and Immunogen outside the submitted work. KM reports personal fees from Astra-Zeneca, AbbVie, Aravive, Eisai, GSK/Tesaro, Genentech/Roche, Immunogen, Merck, Myriad, Mersana, VBL Therapeutics, Vavotar and Tarveda, outside the submitted work. AOaknin reports personal fees, other and grants from PharmaMar and Clovis Oncology, personal fees and other from Roche and AstraZeneca, personal fees and grants from Tesaro and Immunogen, personal fees from Genmab, and grants from AbbVie Deutchland, Ability Pharmaceuticals, Advaxis, Æterna Zentaris, Amgen SA, Aprea Therapeutics AB, Eisai, F. Hoffmann-La Roche, Regeneron, Merck Sharp & Dohme de España SA, Millennium Pharmaceuticals and Bristol Myers Squibb, outside the submitted work. MF reports grants, personal fees and other from AstraZeneca, grants and personal fees from Novartis, personal fees from Takeda, GSK, Lilly and MSD, and other from AbbVie, outside the submitted work. AF reports personal fees and other from AstraZeneca, MSD and GSK outside the submitted work. ALeary reports grants and personal fees from AstraZeneca, Clovis Oncology, MSD, Tesaro, GSK and Ability, personal fees from Biocad and Zentalis, and grants from Iovance, Agenus, Sanofi, Inivata and Roche, outside the submitted work. GSS reports institutional reimbursement for patient accrual and medical writing assistance from AstraZeneca during the conduct of the study, and institutional research support from Merck, Novartis and Roche outside the submitted work. CG reports grants from AstraZeneca during the conduct of the study; grants and personal fees from AstraZeneca, Clovis Oncology, Tesaro, Nucana and Sierra Oncology, grants from Aprea and Novartis, and personal fees from Roche, Foundation One, Chugai, MSD and Cor2Ed, outside the submitted work; and patents for molecular diagnostic tests for cancer. SB reports grants and personal fees from AstraZeneca and Tesaro, personal fees from Clovis Oncology, GSK, MSD, Pfizer, Mersana, Merck Serono, Roche, Seattle Genetics, Genmab, Amgen and Immunogen, and other from Nucana, outside the submitted work. AOza reports being a principal investigator of investigator-initiated studies with AstraZeneca, that his institution has received grant funding from AstraZeneca, and being a steering committee member (noncompensated) for trials with AstraZeneca, Clovis Oncology, Tesaro and Merck. AGM reports personal fees from Amgen, AstraZeneca, Clovis Oncology, Genmab, Immunogen, MSD, Novartis, Oncoinvent, Pfizer/Merck, PharmaMar, Roche and Sotio and grants and personal fees from GSK-Tesaro, outside the submitted work. CA reports personal fees from AstraZeneca/Merck, Tesaro, Immunogen, Eisai/Merck, Mersana Therapeutics and Roche, grants from Genentech, and grants and personal fees from AstraZeneca, Clovis Oncology and AbbVie, outside the submitted work. CM reports grants from Syros, Deciphera, AstraZeneca, Astellas Pharma, Tesaro/GSK, Seattle Genetics and Regeneron outside the submitted work. JL reports personal fees from AstraZeneca, Clovis Oncology, Genentech, Regeneron and Tesaro/GSK, and other from Merck, outside the submitted work; and funding to her institution as Principal Investigator on trials from 2X Oncology, Aravive, Arch Oncology, AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, CytomX Therapeutics, GlaxoSmithKline, Regeneron, Surface Oncology, Tesaro and Vigeo Therapeutics. ESL and RB report full-time employment with AstraZeneca during the conduct of the study and AstraZeneca stock ownership. PDS reports personal fees from AstraZeneca outside the submitted work. All other authors (GS, ALisyanskaya, WB and JWK) declare no competing interests.