For patients with BRCA1/BRCA2-mutated (BRCAm), platinum-sensitive relapsed ovarian cancer (PSROC), and 2 prior lines of platinum-based chemotherapy, the SOLO3 phase III trial found that treatment with olaparib significantly improved objective response rates (ORRs) and progression-free survival (PFS) compared to non-platinum chemotherapy. The LIGHT study prospectively assessed the efficacy of olaparib treatment in patients with PSROC and known BRCAm and homologous recombination deficiency (HRD) status. Patients with PSROC and greater than or equal to 1 prior course of platinum-based chemotherapy were divided into cohorts in this phase II open-label multicenter research based on whether their tumors tested positive for the heritable mutations in the cyclin-dependent kinase oncogene or not. An ORR, as determined by investigators, was the primary outcome. Disease control rate (DCR) and PFS were used as secondary objectives. Investigators used the Myriad BRACAnalysis CDx and myChoice HRD assays to look at the mutational landscape of the malignancies, with HRD-positive tumors being those with a genomic instability score of greater than or equal to 42. A total of 271 individuals who were enrolled got olaparib, and 270 of them were included in the analysis of effectiveness. When the data stopped being collected, the ORRs for patients in the gBRCAm, sBRCAm, HRD-positive, and HRD-negative groups were 69.3%, 64.0%, 29.4%, and 10.1%, respectively. For the 4 groups studied, the DCRs were 96.0%, 100.0%, 79.4%, and 75.3%. 11.0, 10.8, 7.2, and 5.4 months were the respective median PFS values. Nausea, lethargy, vomiting, anemia, constipation, diarrhea, and decreased appetite were the most prevalent treatment-emergent side effects (20%). There was efficacy for olaparib therapy in all groups. BRCAm cohorts showed the highest efficacy irrespective of gBRCAm/sBRCAm status. The HRD-positive cohorts performed better than the HRD-negative cohorts for patients lacking a BRCAm. The safety concerns were similar to those shown in earlier olaparib research.

Source: sciencedirect.com/science/article/pii/S0090825822004218