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Maintenance olaparib following platinum-based chemotherapy in newly diagnosed patients (pts) with advanced ovarian cancer (OC) and a BRCA1/2 mutation (BRCAm): Phase III SOLO1 trial

2018; Elsevier BV; Volume: 29; Linguagem: Inglês

10.1093/annonc/mdy424.041

1569-8041

Kathleen N. Moore, Nicoletta Colombo, Giovanni Scambia, B.-G. Kim, Ana Oaknin, Michael Friedlander, Alla Lisyanskaya, Anne Floquet, Alexandra Léary, Gabe S. Sonke, Charlie Gourley, Susana Banerjee, Amit M. Oza, Antonio González‐Martín, Carol Aghajanian, William H. Bradley, Elizabeth Lowe, Ralph Bloomfield, Paul DiSilvestro,

BRCA gene mutations in cancer

Background: Pts with newly diagnosed advanced OC are treated with cytoreductive surgery and platinum-based chemotherapy. Most relapse within the first 3 years and have further chemotherapy, but once relapsed are largely not curable. SOLO1 (NCT01844986) is the first Phase III trial to evaluate PARP inhibitor (olaparib [Lynparza®]) maintenance therapy after platinum-based chemotherapy in newly diagnosed advanced OC with a BRCAm. Methods: SOLO1 is a randomized, controlled, double-blind trial. Eligible pts had newly diagnosed, FIGO stage III–IV, high-grade serous or endometrioid ovarian, primary peritoneal and/or fallopian tube cancer with a BRCAm, had received platinum-based chemotherapy and were in clinical complete or partial response. Pts were randomized 2:1 to olaparib tablets 300 mg bd or placebo. The primary endpoint was investigator-assessed progression-free survival (PFS; modified RECIST v1.1). Results: Of 391 randomized pts, 260 received olaparib and 130 placebo (one pt did not receive placebo). Median follow-up was 41 months. Baseline characteristics were well balanced. Primary PFS analysis showed a significant 70% reduction in the risk of progression or death with olaparib versus placebo (Table). PFS sensitivity analyses, second PFS and time to first subsequent therapy or death support the primary analysis. Overall survival data are immature. Adverse events were mostly low grade. The most common grade ≥3 toxicities with olaparib were anaemia (22%) and neutropenia (8%). Olaparib dose reductions, interruptions and discontinuations occurred in 28%, 52% and 12%, respectively. There was no change from baseline in health-related quality of life scores with olaparib.Table: LBA7_PRMedian, monthsHR (95% CI) P valueOlaparib (N = 260)Placebo (N = 131)Between-group differencePFS, investigator assessed (51% maturity)NR13.8NC0.30 (0.23–0.41) P < 0.0001PFS, BICR*Sensitivity analysis using BICR BICR, blinded independent central review; HR, hazard ratio; NC, not calculable; NR, not reached; PFS, progression-free survival; PFS2, time from randomization to second progression or death; TFST, time to first subsequent therapy or death (38% maturity)NR14.1NC0.28 (0.20–0.39) P < 0.0001TFST51.815.136.70.30 (0.22–0.40) P < 0.0001PFS2 (31% maturity)NR41.9NC0.50 (0.35–0.72) P = 0.0002* Sensitivity analysis using BICR BICR, blinded independent central review; HR, hazard ratio; NC, not calculable; NR, not reached; PFS, progression-free survival; PFS2, time from randomization to second progression or death; TFST, time to first subsequent therapy or death Open table in a new tab Conclusions: Maintenance olaparib led to a substantial, unprecedented improvement in PFS, with an estimated difference in median PFS for olaparib versus placebo of approximately 3 years. Clinical trial identification: NCT01844986 - July 2018. Editorial acknowledgement: Editorial assistance was provided by Gillian Keating, Mudskipper Business Limited, funded by AstraZeneca and Merck & Co., Inc. Legal entity responsible for the study: AstraZeneca and Merck & Co., Inc. Funding: AstraZeneca; Part of an alliance between AstraZeneca and Merck & Co., Inc. Disclosure: K.N. Moore: Fees for advisory boards: AstraZeneca, Advaxis, Clovis, Tesaro, Genentech/Roche, Immunogen, VBL Therapeutics, Janssen. N. Colombo: Honoraria: Genetech, AstraZeneca, PharmaMar; Fees for consulting/advisory boards: Genentech, PharmaMar, AstraZeneca, Clovis Oncology, Pfizer, MSD, Tesaro; Research funding: AstraZeneca. G. Scambia: Fees for advisory boards: Roche, AstraZeneca, PharmaMar, Clovis Oncology, Tesaro. A. Oaknin: Fees for advisory boards: Roche, AstraZeneca, PharmaMar, Clovis Oncology, Tesaro; Support for travel/accommodation: Roche, AstraZeneca, PharmaMar. M. Friedlander: Fees for advisory boards: AstraZeneca, MSD. A. Floquet: Fees for advisory boards: AstraZeneca, Roche, Tesaro; Support for travel: Roche. A. Leary: Fees for advisory boards: Clovis, AstraZeneca, GamaMabs, Pfizer, Gridstone; Support for travel: AstraZeneca; Preclinical research support: Merus, GamaMabs, Sanofi. G.S. Sonke: Research funding: AstraZeneca, Merck, Novartis, Roche. C. Gourley: Fees for advisory role: Roche, AstraZeneca, Tesaro, Nucana, Clovis, Foundation One; Lecture fees: AstraZeneca; Research funding: Novartis, Aprea, AstraZeneca, Tesaro, Clovis. S. Banerjee: Research funding: AstraZeneca; Fees for advisory boards: AstraZeneca, Tesaro, Clovis. A.M. Oza: Honoraria: Intas Pharma. A. González-Martín: Fees for speaker role/advisory boards: AstraZeneca, Tesaro, Roche, Clovis, PharmaMar. C. Aghajanian: Honoraria and fees for advisory boards: Tesaro, Cerulean, Bayer, VentiRx, Mateon Therapeutics, Clovis; Honoraria and fees for steering committee meetings: Mateon Therapeutics, Clovis. E.S. Lowe, R. Bloomfield: Employee of AstraZeneca and owns stock. P. DiSilvestro: Consulting fees: Astra Zeneca ($1800), Tesaro ($600) over the last 2 years. All other authors have declared no conflicts of interest.