Real-world efficacy and toxicity of olaparib maintenance therapy in Korean ovarian cancer patients with an exploratory analysis of BRCA mutations

Abstract

Objective

To evaluate the real-world efficacy and toxicity of olaparib maintenance therapy in Korean patients with BRCA-mutated ovarian cancer (OC), with an exploratory analysis of BRCA mutations.

Methods

We conducted a retrospective analysis of Korean BRCA-mutated OC patients treated with olaparib maintenance therapy as first-line (1Lm) or second−/subsequent-line (2Lm +) at Asan Medical Center, South Korea, from August 2015 to April 2023. Survival outcomes, including progression-free survival (PFS) and overall survival (OS), as well as toxicity, were analyzed with patient characteristics and BRCA mutations.

Results

In 1Lm (n = 70), the 2-year PFS was 75.5 % and the 3-year OS was 98.5 %. In 2Lm + (n = 83), the 2-year PFS was 54.8 % and the 3-year OS was 87.3 %. The pathogenic p.Leu1780Pro BRCA1 mutation was a poor prognostic factor for PFS in 1Lm (hazard ratio [HR], 5.66). In 2Lm +, platinum-free interval ≥ 12 months was associated with better PFS (adjusted HR [aHR], 0.48) and OS (aHR, 0.31), whereas CA-125 ≥ 10 IU/mL at olaparib initiation was a poor prognostic factor (aHR, 2.12). A longer time interval between the last chemotherapy and maintenance therapy in 1Lm correlated with reduced hematologic toxicity ≥ grade 3 (odd ratio, 0.75) during maintenance therapy. Drug discontinuation due to toxicity occurred in 1.4 % of 1Lm and 6.0 % of 2Lm + .

Conclusions

Olaparib maintenance therapy was effective and tolerable in Korean BRCA-mutated OC patients, though the poor prognosis of the p.Leu1780Pro BRCA1 mutation in 1Lm warrants further investigation.