STUDY 19

Background

Study 19 was the pivotal phase II RCT establishing proof-of-concept for olaparib maintenance in platinum-sensitive relapsed high-grade serous ovarian cancer, providing the first clinical evidence that PARP-inhibitor maintenance could significantly delay progression after a response to platinum.

Interventions and follow up

Arm A: Olaparib 400mg PO BID (capsule) maintenance
Arm B: Placebo
Primary endpoint: progression-free survival
mFollow-up: ~5.9yr (final OS analysis)

Results

mPFS, ITT (n=265): 8.4 vs 4.8mo (HR 0.35, 95% CI 0.25–0.49, P<.001)
mPFS, BRCA-mutated (n=136, exploratory): 11.2 vs 4.3mo (HR 0.18, 95% CI 0.10–0.31)
mOS, ITT: 29.8 vs 27.8mo (HR 0.94, NS)
mOS, BRCAm (updated): 34.9 vs 26.8mo (HR 0.62, P=.025)

Adverse events

Most common (any grade, olaparib): nausea 68%, fatigue 49%, vomiting 32%, anemia
Grade ≥3: overall 36% vs 20%; fatigue 6% vs 5%, anemia 5% vs 0%, vomiting 4% vs 2%. Dose interruption/reduction more frequent with olaparib.

Conclusions

Olaparib maintenance significantly prolonged PFS versus placebo in platinum-sensitive relapsed ovarian cancer, with greatest benefit in BRCA-mutated patients, establishing the paradigm for biomarker-selected PARP-inhibitor maintenance.

Key Limitations

Phase II, not powered for OS; BRCA subgroup analyses were exploratory and retrospectively defined as BRCA testing matured. No formal OS benefit in the ITT population, confounded by substantial crossover. Capsule formulation later superseded by tablets; superseded as confirmatory evidence by SOLO-2.

Clinical Context

Study 19 underpinned the EMA approval of olaparib maintenance in BRCA-mutated platinum-sensitive relapsed ovarian cancer and informed subsequent confirmatory trials (SOLO-2, NOVA, ARIEL3). It cemented BRCA/HRD testing in ovarian cancer management and the maintenance treatment concept now standard across the disease.

References