LBA3 - 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

Abstract

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 datTableLBA3Median, monthsHR (95% CI)Olaparib (N = 260)Placebo (N = 131)Between-group differenceP valuePFS, investigator assessedNR13.8NC0.30 (0.23–0.41)P < 0.0001(51% maturity)PFS, 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 deathNR14.1NC0.28 (0.20–0.39)(38% maturity)P < 0.0001TFST51.815.136.70.30 (0.22–0.40)P < 0.0001PFS2NR41.9NC0.50 (0.35–0.72)(31% maturity)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 a 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. 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. Editorial acknowledgement: Gillian Keating, MBChB, from Mudskipper Business Ltd, funded by AstraZeneca and Merck & Co., Inc. Clinical trial identification: NCT01844986, 26 August 2013. Legal entity responsible for the study: AstraZeneca. Funding: AstraZeneca. Disclosure: M. Friedlander: Personal fees for advisory boards: AZ and MSD. K. Moore: Consultancy: Tesaro, Genentech Roche, Clovis, Immunogen, VBL Therapeutics, Janssen (honorarium, ad board), AstraZeneca - honorarium, ad board (for agents not involved in the SOLO-1 study). N. Colombo: Honoraria: Genentech, Astra Zeneca, PharmaMar; Consulting or advisory role: Genentech, PharmaMar, AstraZeneca, Clovis Oncology, Pfizer, MSD, Tesaro; Research funding: AstraZeneca. G. Scambia: Fees for advisory role: Roche, AstraZeneca, PharmaMar, Clovis Oncology, Tesaro. A. Oaknin: Fees for advisory board: Roche, AstraZeneca, PharmaMar, Clovis Oncology, Tesaro; Travel/accommodation: Roche, AstraZeneca, PharmaMar. A. Floquet: Fees for advisory board: Astra Zeneca, Roche, Tesaro; Support travel: Roche. A. Leary: Ad boards: Clovis, AstraZeneca, Gamamabs, Pfizer, Gridstone; Travel costs: AstraZeneca; Preclinical research support: Merus, Gamamabs, Sanofi. G.S. Sonke: Institutional research support: AstraZeneca, Merck, Novartis, Roche. C. Gourley: Fees for advisory role: Roche, AstraZeneca, Tesaro, Nucana, Clovis, Foundation One; Lecture fees: AstraZeneca; Research funding (to my institution): Novartis, Aprea, AstraZeneca, Nucana, Tesaro. S. Banerjee: Research funding: AstraZeneca; Advisory boards: AstraZeneca, Tesaro, Clovis. A.M. Oza: Steering committees for trials: AstraZeneca, Clovis, Tesaro (all non-compensated); Honoraria: Intas Pharma. A. González-Martín: Grants as speaker/advisory board participants (last 36 months): AstraZeneca, Tesaro, Roche, Clovis, Pharmamar. C. Aghajanian: Consultancy: Tesaro, Cerulean, Bayer, VentiRx (honorarium, ad board); Mateon Therapeutics (honorarium steering committee meetings); Clovis (honorarium ad boards and steering committee meeting). W. Bradley: Fee for advisory role: Celsion E.S. Lowe, R. Bloomfield: Employee and stockholder: AstraZeneca. P. Disilvestro: Consulting fees: AstraZeneca and Tesaro (over last 2 years). All other authors have declared no conflicts of interest.