Background
Phase III, double-blind, placebo-controlled RCT. 391 patients with newly diagnosed advanced (FIGO III/IV) BRCA1/2-mutated high-grade ovarian, fallopian tube, or primary peritoneal cancer who had a complete or partial response after first-line platinum-taxane chemotherapy. Randomized 2:1 to olaparib or placebo.
Interventions and follow up
Arm A: Olaparib 300 mg PO BID maintenance up to 24 months
Arm B: Placebo
Primary endpoint: Investigator-assessed PFS
mFollow up: 41 months
Arm B: Placebo
Primary endpoint: Investigator-assessed PFS
mFollow up: 41 months
Results
mPFS: not reached vs 13.8 months (Arm A vs Arm B), HR 0.30, 95%CI 0.23-0.41, P<.001
3-yr PFS: 60% vs 27% (Arm A vs Arm B)
5-yr PFS (updated analysis): 48.3% vs 20.6%, HR 0.48
3-yr PFS: 60% vs 27% (Arm A vs Arm B)
5-yr PFS (updated analysis): 48.3% vs 20.6%, HR 0.48
Adverse events
Hematologic (grade ≥3, Arm A vs Arm B): anemia 22% vs 2%; neutropenia 8% vs 4%
Non-hematologic (Arm A vs Arm B): grade ≥3 fatigue 4% vs 2%; any-grade nausea 76% vs 35%; treatment discontinuation due to AEs 12% vs 2%
Non-hematologic (Arm A vs Arm B): grade ≥3 fatigue 4% vs 2%; any-grade nausea 76% vs 35%; treatment discontinuation due to AEs 12% vs 2%
Conclusions
Olaparib maintenance significantly prolonged PFS in newly diagnosed BRCA1/2-mutated advanced ovarian cancer, with a 70% reduction in risk of progression. Benefit was durable, with approximately half of patients progression-free at 5 years.
Key Limitations
Restricted to BRCA1/2-mutated patients (~15-20% of all ovarian cancer). OS data were immature at initial reporting. No bevacizumab allowed, so cannot be directly compared to PAOLA-1. The 24-month cap on olaparib duration was arbitrary and may have underestimated benefit from indefinite maintenance.
Clinical Context
SOLO-1 established olaparib as the standard first-line maintenance for BRCA1/2-mutated advanced ovarian cancer and defined the foundation of the PARP inhibitor maintenance era. FDA approved 2018; ESMO-MCBS score: A. Now complemented by PAOLA-1 (olaparib + bevacizumab) for patients who received bevacizumab during first-line chemotherapy.