Background
Phase III RCT (STUDY 19/SOLO2). 295 patients with platinum-sensitive relapsed high-grade serous or BRCA-mutated ovarian cancer who had received ≥2 prior platinum-based regimens and had a complete or partial response to their most recent platinum-based regimen. Randomized 2:1 to olaparib 300 mg BID (tablets) maintenance until progression vs placebo. BRCA1/2 mutation required (germline and/or somatic). OS update published 2020 (Poveda LO). This was the definitive maintenance trial for BRCA-mutated platinum-sensitive recurrent ovarian cancer.
Interventions and follow up
Arm A: Olaparib 300 mg BID tablets until progression or unacceptable toxicity
Arm B: Placebo
Primary endpoint: PFS by blinded independent central review
mFollow up: 22.1 months (PFS); 65.7 months (OS update)
Arm B: Placebo
Primary endpoint: PFS by blinded independent central review
mFollow up: 22.1 months (PFS); 65.7 months (OS update)
Results
Median PFS: 19.1 months (olaparib) vs 5.5 months (placebo), HR 0.30 (95% CI 0.22–0.41), P<.0001
Median OS (updated): 51.7 months (olaparib) vs 38.8 months (placebo), HR 0.74 (95% CI 0.54–1.00), P=.054 — borderline significant
ORR in measurable disease: 72% (olaparib) vs 32% (placebo)
Median OS (updated): 51.7 months (olaparib) vs 38.8 months (placebo), HR 0.74 (95% CI 0.54–1.00), P=.054 — borderline significant
ORR in measurable disease: 72% (olaparib) vs 32% (placebo)
Adverse events
Main adverse events: Grade ≥3 AEs: 43% (olaparib) vs 18% (placebo). Grade ≥3 anemia: 19% vs 2%. Grade ≥3 fatigue: 4% vs 2%. MDS/AML: 8% (olaparib) vs 4% (placebo) — notably higher than SOLO1, possibly due to more heavily pretreated population. Discontinuation due to AEs: 11% vs 2%.
Conclusions
Olaparib maintenance dramatically improved PFS (HR 0.30; 19.1 vs 5.5 months) in BRCA-mutated platinum-sensitive recurrent ovarian cancer, with a non-significant trend toward OS benefit (HR 0.74). Olaparib is standard maintenance after response to platinum-based therapy in BRCA-mutated recurrent ovarian cancer.
Key Limitations
Key Limitations: OS benefit did not reach statistical significance (P=.054), though the HR of 0.74 represents a clinically meaningful ~13-month median OS gain. The more heavily pretreated population showed higher MDS/AML rates (8%) than first-line trials. Substantial crossover (from placebo to olaparib) complicates OS interpretation. Restricted to BRCA-mutated patients — niraparib (NOVA) is an alternative for all-comer platinum-sensitive recurrent OC.
Clinical Context
SOLO2 is the key trial supporting olaparib maintenance in BRCA-mutated platinum-sensitive recurrent ovarian cancer (FDA approved for this indication). The companion NOVA trial (niraparib) covers broader biomarker groups. Combined PARP inhibitor + bevacizumab has been explored (ODELIA) but is not standard. Patients progressing on prior PARP inhibitor maintenance face limited subsequent PARP inhibitor benefit.
References