L-MOCA: Olaparib maintenance for ovarian cancer benefits Asians

Maintenance monotherapy with olaparib appears safe and effective in Asian patients with platinum-sensitive relapsed (PSR) ovarian cancer, regardless of their BRCA status, as shown in the results of the phase III, open-label, single-arm L-MOCA study.

After a median follow-up of 15.5 months, maintenance treatment with oral olaparib monotherapy led to a promising duration of median progression-free survival (PFS) of 16.1 months (95 percent confidence interval [CI], 13.3–18.3), according to the investigators.

The PFS rates were 76.0 percent (95 percent CI, 69.8–81.2) at 6 months and 57.1 percent (95 percent CI, 50.2–63.5) at 12 months. [Clin Cancer Res 2022;28:2278-2285]

Subgroup analyses of BRCA status showed that mPFS was 21.2 months (95 percent CI, 16.4–24.9) among patients with BRCA-mutated disease, 11.0 months (95 percent CI, 8.3–15.8) among those with wild-type BRCA, 16.1 months (95 percent CI, 5.9–not evaluable) among those with somatic BRCA mutation, and 21.4 months (95 percent CI, 16.5–24.9) among those with germline BRCA mutation.

Potential predictors of survival included age at first dose (<65 vs ≥65 years: median PFS, 15.8 vs 19.7 months), response to last chemotherapy (complete vs partial response: median PFS, 19.7 vs 13.9 months), number of prior lines of therapy (second- vs third-line anticancer treatment: median PFS, 18.0 vs 8.8 months), and time to disease progression after second-to-last platinum-based chemotherapy (12 months vs 6–12 months: median PFS, 20.9 vs 9.3 months).

Nealy every patient in the cohort (99.1 percent) developed adverse events (AEs) of any grade, with the most common being anaemia (76.4 percent), nausea (54.0 percent), and leukopaenia (24.1 percent). Meanwhile, 48.7 percent of patients had grade ≥3 AEs, including anaemia (25.0 percent), decreased neutrophil count (14.3 percent), and decreased platelet count (4.9 percent). Treatment-related AEs led to olaparib discontinuation in 9.4 percent of patients.

L-MOCA included 224 patients (median age 54 years, 91.5 percent Chinese) with high-grade epithelial PSR ovarian cancer enrolled from country-wide clinical centres across China and Malaysia. Most of them (67.9 percent) had stage III disease at diagnosis, and more than one-third (35.7 percent) had received at least three lines of chemotherapy. Olaparib at 300 mg was given twice daily until disease progression or unacceptable toxicity.

The investigators pointed out that the single-arm design of the study was partly due to the proven efficacy of olaparib compared with placebo and claimed that the baseline demographics and clinical characteristics reported in L-MOCA show that the study population is largely representative of the PSR ovarian cancer population seen in clinical practice. [N Engl J Med 2012;366:1382-1392; Biomed Pharmacother 2020;123:109661; Lancet Oncol 2017;18:1274-1284]

“The clinical benefit of olaparib seen in this study reinforces that observed in global studies and supports its use in patients with PSR ovarian cancer, including Asian patients, regardless of BRCA status. Another subgroup analysis revealed that patients with homologous recombination repair (HRR) mutation had a numerically longer median PFS (18.3 months) than patients with HRR-wild-type disease (13.3 months),” the investigators noted. [Lancet Oncol 2017;18:1274-1284; J Clin Oncol 2021;39:5545; Gynecol Oncol 2021;162:S57; Clin Cancer Res 2021;27:2452-2458]

“There is limited evidence supporting the accuracy of HRR as a biomarker for response to olaparib treatment, and so an exploratory analysis of the association between homologous recombination deficiency (HRD) status and olaparib efficacy will be performed to investigate HRD biomarker status in PSR ovarian cancer,” they added.