Olaparib Maintenance Yields Promising Long-Term OS Outcomes in Asian Patients With Platinum-Sensitive, Relapsed Ovarian Cancer

Maintenance olaparib (Lynparza) produced encouraging long-term overall survival (OS) outcomes and demonstrated a consistent long-term safety profile with no new safety signals in Asian patients with platinum-sensitive relapsed ovarian cancer, according to final findings from the phase 3b L-MOCA trial (NCT03534453).

Findings published in the Journal of Ovarian Research showed that at the January 20, 2025, data cutoff and a median follow-up of 73.4 months (interquartile range [IQR], 60.4-75.2), OS data were at 56.7% maturity. The median OS was 51.0 months (95% CI, 42.7-56.1) in the overall population (n = 224). Notably, median OS was numerically longer among patients with BRCA-mutated disease (n = 106) than among those with BRCA wild-type disease (n = 117), at 64.4 months (95% CI, 49.9-not evaluable [NE]) vs 40.9 months (95% CI, 33.3-51.0), respectively.

Similarly, patients with homologous recombination deficiency (HRD)–positive disease (n = 125) achieved a median OS of 54.4 months (95% CI, 42.5-NE) compared with 34.8 months (95% CI, 28.3-46.4) among those with HRD-negative disease (n = 26). Median OS was 54.6 months (95% CI, 43.3-67.5) among patients who had received 2 prior lines of therapy (n = 144) and 39.5 months (95% CI, 30.1-53.6) among those who had received more than 2 prior lines (n = 80).

“Long-term follow-up data from L-MOCA indicate that olaparib maintenance monotherapy shows promising OS and [a] tolerable safety profile in Asian patients [with platinum-sensitive relapsed ovarian cancer], regardless of BRCA or HRD status,” lead study author Xingzhe Liu, MD, of the National Clinical Research Centre for Obstetrics and Gynaecology, Department of Gynecological Oncology at Huazhong University of Science and Technology in Wuhan, China,0 and colleagues wrote in the publication.

Who was eligible to take part in this trial?

To be eligible for enrollment in L-MOCA, female patients needed to be 18 years of age or older with relapsed, high-grade serous or high-grade endometrioid epithelial ovarian, primary peritoneal, or fallopian tube cancer and an ECOG performance status of 0 or 1.^1,2 Patients were required to have platinum-sensitive disease, defined as progression occurring at least 6 months after the final dose of platinum therapy, and to have achieved a complete or partial response to their most recent platinum-based chemotherapy. Additional requirements included at least 2 prior lines of platinum-based chemotherapy and adequate organ and bone marrow function. Patients who had previously received a PARP inhibitor were excluded.

L-MOCA was a prospective, open-label, single-arm, multicenter phase 3b trial conducted across 37 centers in China and Malaysia. Patients received oral olaparib at 300 mg twice daily as maintenance monotherapy until radiographic disease progression or unacceptable toxicity. Tumor assessments were conducted according to RECIST 1.1 criteria at baseline, every 12 weeks through week 72, and every 24 weeks thereafter. Blood and tumor tissue samples were also collected for BRCA mutation and homologous recombination deficiency testing. Because the trial was single arm, patients were not randomly assigned, and there was no placebo or active-comparator group.

The primary end point was investigator-assessed progression-free survival (PFS) according to RECIST 1.1 criteria. Secondary end points included OS, time from the first dose of olaparib to second disease progression, time to first subsequent treatment or death, time to study treatment discontinuation or death, and time to second subsequent treatment or death.

What are the patient characteristics?

Among the 225 patients enrolled in L-MOCA, 224 received at least 1 dose of olaparib and were included in the full analysis set. All patients were women, and the median age was 54.0 years (IQR, 50.0-61.5). Most patients were Chinese (91.5%), whereas 8.5% were Malaysian. BRCA mutations were detected in 47.3% of patients (n = 106), and among the 190 patients evaluated for homologous recombination deficiency status, 65.8% (n = 125) had HRD-positive disease. At the January 20, 2025, data cutoff, 92.4% of patients (n = 207) had discontinued olaparib, most commonly because of disease progression (62.1%; n = 139), and 70.1% (n = 157) had exited the study.

What additional efficacy data were reported?

The updated investigator-assessed median progression-free survival was 16.2 months (95% CI, 12.5-18.2), which was consistent with the previously reported primary analysis. Additional efficacy findings included a median second progression-free survival of 29.4 months (95% CI, 26.2-32.8), a median time to first subsequent treatment or death of 18.3 months (95% CI, 16.0-20.9), a median time to treatment discontinuation or death of 13.7 months (95% CI, 9.8-15.8), and a median time to second subsequent treatment or death of 34.0 months (95% CI, 30.3-41.4). Although longer median survival times were observed in certain biomarker and treatment-history subgroups, the single-arm design of L-MOCA prevents conclusions regarding an improvement over a comparator.

What is the safety outlook for this trial?

The median duration of exposure to olaparib was 418.5 days (IQR, 170.0-799.0), and the median daily dose was 588.4 mg (IQR, 506.5-597.1). Any-grade treatment-emergent adverse effects (TEAEs) occurred in 98.7% of patients. The most common any-grade TEAEs were anemia (73.7%), nausea (54.0%), and decreased white blood cell count (47.3%). Grade 3 or higher TEAEs were reported in 49.1% of patients, with the most common being anemia (24.1%), decreased neutrophil count (13.8%), and decreased white blood cell count (8.9).

Treatment-related TEAEs occurred in 98.2% of patients and were grade 3 or higher in 44.2%. Serious TEAEs were reported in 26.8% of patients, including treatment-related serious TEAEs in 17.9%. The most common treatment-related serious TEAEs were anemia (10.3%) and myelosuppression (2.2%). TEAEs led to dose adjustments in 63.8% of patients, including dose reductions in 40.2%, and treatment discontinuation in 12.9%. One patient (0.4%) died due to acute myeloid leukemia. Myelodysplastic syndrome or acute myeloid leukemia occurred in 1.3% of patients, with no additional cases identified during approximately 4 additional years of follow-up and no new long-term safety signals observed.

References

1. Liu X, Liu D, Peng Z, et al. 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. J Ovarian Res. 2026;19(1):243. doi:10.1186/s13048-026-02144-4
2. Olaparib tablets maintenance monotherapy ovarian cancer patients after complete or partial response to platinum chemotherapy (L-MOCA). ClinicalTrials.gov. Updated July 10, 2025. Accessed September 17, 2026. https://clinicaltrials.gov/study/NCT03534453