Overall survival and long-term safety of olaparib maintenance in patients with platinum-sensitive relapsed ovarian cancer: final analyses of phase III L-MOCA trial.

Abstract

Background: The indications for Poly(ADP-ribose) polymerase (PARP) inhibitor maintenance therapy in platinum-sensitive recurrent ovarian cancer (PSROC) patients varies across nations. The lack of clinical trial evidence and detailed biomarker analysis in the Asian population results in uncertain clinical benefits. Additionally, the absence of long-term safety monitoring data limits the assessment of tolerance to prolonged PARP inhibitor use.

Methods: This prospective, open-label, single-arm, phase IIIb L-MOCA study enrolled Asian patients with high-grade epithelial PSROC across China and Malaysia. Patients received oral olaparib (300 mg) twice daily until disease progression or unacceptable toxicity. The primary endpoint of progression-free survival has been reported previously. A prespecified final OS analysis was conducted at approximately 60% data maturity.

Results: After a median follow-up of 73.4 months, the median OS (mOS) reached 51.0 months (95% CI, 42.7 to 56.1). The mOS was 64.4 months (49.9 to not reach [NR]) in BRCA-mutated patients and 40.9 months (33.3 to 51.0) in BRCA wild-type patients. The mOS was 54.4 months (42.5 to NE) in HRD-positive patients and 34.8 months (28.3 to 46.6) in HRD-negative patients. No new safety signals were identified compared to the primary L-MOCA report. Myelodysplastic syndrome and acute myeloid leukemia (MDS/AML) occurred in 1.3% of patients, and no additional cases were identified after approximately four additional years of follow-up beyond the primary analysis.

Conclusion: Long-term follow-up data from L-MOCA indicates that olaparib maintenance monotherapy shows promising overall survival and tolerable safety profile in Asian PSROC patients, regardless of BRCA or HRD status.

Trial registration: Registry: ClinicalTrials.gov.