Secondary efficacy data and subgroup analyses from the LIGHT study indicate that olaparib monotherapy was most effective in BRCA-mutated cohorts of patients with platinum-sensitive relapsed ovarian cancer.
The open-label, nonrandomized phase 2 LIGHT (NCT02983799) study evaluated olaparib treatment in patients with platinum-sensitive relapsed ovarian cancer by BRCA mutation (BRCAm) and homologous recombination deficiency (HRD) status. The results of prespecified secondary efficacy end points and subgroup analyses were reported at the 2021 Society of Gynecologic Oncology Annual Meeting.
The study enrolled patients with platinum-sensitive relapsed ovarian cancer who had received ≥1 previous lines of platinum-based chemotherapy. Eligible patients received olaparib monotherapy (300 mg twice a day) and were assigned to 1 of 4 cohorts based on whether they had a germline BRCAm (gBRCAm), somatic BRCAm (sBRCAm), HRD-positive (non-BRCAm) tumors, or HRD-negative tumors. Secondary efficacy end points included investigator-assessed progression-free survival (PFS) and CA-125 response. The time to any progression (TTAP) was defined from the date of the first dose of olaparib until the earliest date of RECIST version 1.1 or CA-125 disease progression, or death. The data cutoff was August 27, 2019.
A total of 271 patients received olaparib; of these, 270 patients had measurable disease at baseline and were included in efficacy analyses. Efficacy in 13 patients was analyzed separately, because they could not be assigned to a cohort as a result of failed or missing Myriad test results. In patients with ≥1 previous lines of chemotherapy, objective response rates of approximately 60% to 70% were achieved in the BRCAm cohorts, and approximately 30% in the non-BRCAm cohort; median PFS was approximately 10 to 11 months in the BRCAm cohorts, and 5 to 7 months in the non-BRCAm cohort. A high proportion of patients in the BRCAm cohorts achieved a CA-125 response and complete response, with a CA-125 complete response rate of 60% to 68%, compared with 29% in the non-BRCAm cohort. Median TTAP was approximately 11 months in the BRCAm cohorts and 7.2 months in the non-BRCAm cohort.
Results of this multicohort study indicate that olaparib monotherapy was most effective in BRCAm cohorts of patients with platinum-sensitive relapsed ovarian cancer.
Source: Cadoo K, Simpkins F, Mathews C, et al. Olaparib treatment in patients with platinum-sensitive relapsed ovarian cancer by BRCA mutation and homologous recombination deficiency status: secondary safety results from the phase II LIGHT study. Gynecol Oncol. 2021;162(suppl_1):S67-S68.