Background
Phase III RCT (SOLO1). 391 patients with newly diagnosed BRCA1- or BRCA2-mutated advanced (stage III-IV) high-grade serous or endometrioid ovarian, fallopian tube, or primary peritoneal cancer who had complete or partial response to first-line platinum-based chemotherapy. Randomized 2:1 to olaparib maintenance (300 mg BID × up to 2 years) vs placebo. Olaparib is a PARP inhibitor that exploits synthetic lethality in BRCA-deficient tumors. This trial established PARP inhibitor maintenance as standard after first-line chemotherapy in BRCA-mutated ovarian cancer.
Interventions and follow up
Arm A: Olaparib 300 mg BID (up to 2 years) maintenance after CR/PR to platinum-based chemo
Arm B: Placebo (up to 2 years)
Primary endpoint: Progression-free survival (PFS) by investigator assessment
mFollow up: 5-year update (Banerjee NEJM 2023)
Arm B: Placebo (up to 2 years)
Primary endpoint: Progression-free survival (PFS) by investigator assessment
mFollow up: 5-year update (Banerjee NEJM 2023)
Results
Median PFS: Not reached (olaparib) vs 13.8 months (placebo), HR 0.30 (95% CI 0.23–0.41), P<.001
5-year PFS rate: 48.3% (olaparib) vs 20.6% (placebo)
7-year OS update: HR 0.55 (95% CI 0.40–0.76), P<.001 — significant OS benefit confirmed
5-year PFS rate: 48.3% (olaparib) vs 20.6% (placebo)
7-year OS update: HR 0.55 (95% CI 0.40–0.76), P<.001 — significant OS benefit confirmed
Adverse events
Main adverse events: Grade ≥3 AEs: 36% (olaparib) vs 18% (placebo). Most common grade ≥3: anemia (22% vs 2%), fatigue (4% vs 2%), nausea (1% vs <1%). Discontinuation due to AEs: 12% vs 2%. No increased risk of MDS or AML vs placebo at follow-up. Myelodysplastic syndrome: 2% (olaparib) vs 0% (placebo) — low but notable.
Conclusions
Olaparib maintenance after first-line platinum-based chemotherapy dramatically improved PFS in BRCA-mutated ovarian cancer (HR 0.30), with ~28% absolute difference in 5-year PFS (48% vs 21%), and demonstrated significant OS benefit at 7-year follow-up — establishing olaparib maintenance as the standard of care in this population.
Key Limitations
Key Limitations: Restricted to BRCA1/2-mutated patients (germline or somatic) — not applicable to BRCA wild-type ovarian cancer. Olaparib duration was capped at 2 years — optimal treatment duration uncertain, and many patients developed progression within the first 2 years. Long-term PARP inhibitor exposure raises concerns about hematologic malignancy risk (MDS/AML) with extended follow-up. Trial conducted before HRD testing was standardized — BRCA mutation, not HRD score, was the eligibility criterion.
Clinical Context
SOLO1 is the landmark trial defining BRCA-mutated first-line ovarian cancer management. Olaparib 300 mg BID maintenance for 2 years after first-line platinum-based chemotherapy is now standard of care (FDA approved 2018, NCCN Category 1). PAOLA-1 (olaparib + bevacizumab) extends benefit to HRd/BRCA-mutated patients also receiving bevacizumab. PRIMA (niraparib) and VELIA (veliparib) cover broader HRd populations.