Final overall survival (OS) results from SOLO2/ENGOT-ov21: A phase III trial assessing maintenance olaparib in patients (pts) with platinum-sensitive, relapsed ovarian cancer and a BRCA mutation.

Abstract

6002 Background: SOLO2 (ENGOT ov-21; NCT01874353) showed that maintenance therapy with the PARP inhibitor olaparib in pts with platinum-sensitive relapsed ovarian cancer (PSROC) and a BRCA mutation (BRCAm) led to a statistically significant improvement in median progression-free survival (PFS) of 13.6 months vs placebo (hazard ratio [HR] 0.30). Time to second progression or death significantly improved (Pujade-Lauraine et al Lancet Oncol 2017) and a quality-adjusted PFS benefit was seen (Friedlander et al Lancet Oncol 2018) with maintenance olaparib vs placebo. We report the preplanned final OS analysis for SOLO2. Methods: Pts with PSROC and a BRCAm who had received ≥2 lines of treatment and were in response to their most recent platinum-based chemotherapy received maintenance olaparib (300 mg bid tablets) or placebo. Pts were stratified by response to previous chemotherapy (complete vs partial) and length of platinum-free interval (>6–12 months vs >12 months). OS was a secondary endpoint. The only preplanned OS sensitivity analysis was an OS analysis in the Myriad germline BRCAm subset (Myriad BRAC Analysis test). Results: At final data cut-off (Feb 3, 2020), median follow-up was 65 months in both treatment arms. A long-term treatment benefit was seen with olaparib vs placebo with an OS HR of 0.74 (95% confidence interval [CI] 0.54–1.00) in the full analysis set (FAS; unadjusted for crossover; 38.4% of placebo pts crossed over to a PARP inhibitor) (Table). At 5 years: by Kaplan-Meier estimates, 28.3% of pts in the olaparib arm vs 12.8% of pts in the placebo arm were alive and had still not received subsequent treatment; 42.1% of olaparib pts vs 33.2% of placebo pts were alive. The long-term tolerability profile of olaparib was generally consistent with that reported previously. Conclusions: In the final analysis of SOLO2, maintenance olaparib provided an unprecedented improvement of 12.9 months in median OS vs placebo. This is the first study with olaparib tablets, and the first since Study 19 (NCT00753545), to provide long-term follow-up and final OS data in pts with PSROC and a BRCAm. Clinical trial information: NCT01874353. [Table: see text]

Therapeutic options following second-line platinum-based chemotherapy in patients with recurrent ovarian cancer: Comparison of active surveillance and maintenance treatment

“…Hematologic AEs may be considered a class effect of PARP inhibitors, with anemia being the most common (any grade: 21-50%; grade ≥3: 5-25%), followed by thrombocytopenia (any grade: < 10-61%; grade ≥3: < 3-34%), and neutropenia (any grade: 5-30%; grade ≥3: 4-20%). The incidence of myelodysplastic syndrome or acute myeloid leukemia observed with all three PARP inhibitors is low (1-2%) [20,21,38]; however, in the final OS analysis of SOLO2, the incidence was 8% with olaparib (mean treatment duration: 29.1 months) versus 4% with placebo (mean treatment duration: 18.6 months) [43].…”

“…Although OS was numerically longer with the addition of bevacizumab maintenance to chemotherapy versus chemotherapy alone, no statistically significant survival benefit was observed in OCEANS ( [42]. Median OS in SOLO2 was also longer with olaparib than placebo (51.7 vs 38.8 months; HR 0.74 [95% CI 0.54-1.00]; P = 0.0537) [43]. OS data for NOVA and ARIEL3 are not yet mature.…”

“…Postprogression efficacy outcomes in clinical studies of PARP inhibitors as second-line maintenance treatments in patients with recurrent ovarian cancer[19,21,[38][39][40]42,43].…”

The Efficacy and Safety of Niraparib for Advanced Ovarian Cancer: A Single-center Observational Study From China

“…The median prior line was 5 (3)(4)(5)(6)(7)(8) in the exploratory multi-line therapy group. Ultimately therapeutic evaluation showed that two patients achieved partial response (PR), one patient achieved stable disease (SD) and three patients had progressive disease (PD), yielding the objective response rate (ORR) of 33.3%…”

“…How to prolong the platinum free interval (PFI) becomes one of the breakthrough points in ovarian cancer treatment. Recently, poly ADP-ribose Polymerase (PARP) inhibitors have changed the treatment paradigm for ovarian cancer that can signi cantly improve the platinum free interval, and nally prolong the overall survival of patients with BRCA mutation [3][4][5][6].…”