Background
SOLO-2 (ENGOT-Ov21) was a phase III double-blind, placebo-controlled trial (n=295) evaluating olaparib tablet (300 mg BID) as maintenance therapy in patients with platinum-sensitive, relapsed high-grade serous or endometrioid ovarian cancer and a germline BRCA1/2 mutation (gBRCAm), after complete or partial response to platinum. The OS analysis (Poveda et al, Lancet Oncol 2021) represents the longest survival follow-up of any PARP inhibitor maintenance trial in the platinum-sensitive recurrent setting.
Interventions and follow up
Arm A (placebo): Placebo BID until progression
Arm B (olaparib): Olaparib 300 mg PO BID until progression
Primary endpoint: Investigator-assessed PFS (RECIST v1.1); OS reported as secondary endpoint
Median follow-up: 65.7 months (OS analysis)
Arm B (olaparib): Olaparib 300 mg PO BID until progression
Primary endpoint: Investigator-assessed PFS (RECIST v1.1); OS reported as secondary endpoint
Median follow-up: 65.7 months (OS analysis)
Results
mPFS (primary, 2017): 19.1 (olaparib) vs 5.5 months; HR 0.30, 95% CI 0.22–0.41, P<.0001
mOS (final 2021): 51.7 vs 38.8 months; HR 0.74, 95% CI 0.54–1.00, P=.054 (did not reach pre-specified significance; +12.9-month absolute gain)
5-yr OS: 42% vs 33%
mOS (final 2021): 51.7 vs 38.8 months; HR 0.74, 95% CI 0.54–1.00, P=.054 (did not reach pre-specified significance; +12.9-month absolute gain)
5-yr OS: 42% vs 33%
Adverse events
Hematologic: Anemia 21%, neutropenia 7%; long-term MDS/AML in 8 (4%) olaparib vs 4 (4%) placebo
Other: Fatigue 4%, nausea 3%; no new or unexpected toxicities during extended follow-up
Other: Fatigue 4%, nausea 3%; no new or unexpected toxicities during extended follow-up
Conclusions
Olaparib maintenance provides a clinically meaningful but statistically non-significant OS benefit (+12.9 months, HR 0.74) in gBRCAm platinum-sensitive recurrent ovarian cancer, with a striking mPFS improvement (HR 0.30) on the primary endpoint. The OS analysis was likely confounded by substantial crossover (~38% of placebo patients received subsequent PARP inhibitor therapy).
Key Limitations
OS did not reach pre-specified statistical significance (P=.054); crossover from placebo to subsequent PARP inhibitor attenuates the OS comparison; gBRCAm-only population limits generalizability (see Study 19 and NOVA for broader HRD populations); olaparib tablet (300 mg BID) vs capsule (400 mg BID) formulation differs from Study 19; OS follow-up of ~5.5 years is the longest in recurrent-ovarian PARP inhibitor data.
Clinical Context
SOLO-2 was the pivotal trial supporting FDA approval of olaparib tablets for gBRCAm platinum-sensitive recurrent ovarian cancer maintenance (2017). The 5-yr OS data from the 2021 analysis provide reassurance of durable long-term benefit despite not crossing the formal OS significance boundary. SOLO-2 occupies the same niche as Study 19 but is larger, prospectively enrolls only gBRCAm patients, and uses the current tablet formulation. SOLO-2, Study 19, NOVA, and ARIEL3 collectively established PARP inhibitor maintenance as standard of care across platinum-sensitive recurrent ovarian cancer biomarker strata; ESMO guidance reflects this.
References
Poveda A et al, Lancet Oncol, 2021; PMID: 33743851
Pujade-Lauraine E et al, Lancet Oncol, 2017 (primary PFS); PMID: 28754483
Pujade-Lauraine E et al, Lancet Oncol, 2017 (primary PFS); PMID: 28754483