Olaparib treatment for platinum-sensitive relapsed ovarian cancer by BRCA mutation and homologous recombination deficiency status: Phase II LIGHT study primary analysis

Objective. Olaparib treatment resulted in significant improvement in objective response rates (ORRs) and progression-free survival (PFS) over non-platinum chemotherapy in patients with BRCA1/BRCA2- mutated (BRCAm) platinum-sensitive relapsed ovarian cancer (PSROC) and >= 2 prior lines of platinum -based chemotherapy in the phase III SOLO3 study. LIGHT (NCT02983799) prospectively evaluated olaparib treatment for patients with PSROC and known BRCAm and homologous recombination deficiency (HRD) status.Methods. In this phase II open-label multicenter study, patients with PSROC and >= 1 prior line of platinum-based chemotherapy were assigned to cohorts by presence of germline BRCAm (gBRCAm), so-matic BRCAm (sBRCAm), HRD-positive tumors without BRCAm, or HRD-negative tumors. The primary end-point was investigator-assessed ORR. Secondary endpoints included disease control rate (DCR) and PFS. Tumors were analyzed using Myriad BRACAnalysis CDx and myChoice HRD assays; HRD-positive tumors were defined using a genomic instability score of >= 42.Results. Of 272 enrolled patients, 271 received olaparib and 270 were included in efficacy analyses. At data cut-off, ORRs in the gBRCAm, sBRCAm, HRD-positiv e, and HRD-negative cohorts were 69.3%, 64.0%, 29.4%, and 10.1%, respectively. DCRs were 96.0%, 100.0%, 79.4%, and 75.3% in each cohort, respectively. Median PFS was 11.0, 10.8, 7.2, and 5.4 months, respectively. The most common (>= 20%) treatment -emergent adverse events included nausea, fatigue/asthenia, vomiting, anemia, constipation, diarrhea, and decreased appetite.Conclusions. Olaparib treatment demonstrated activity across all cohorts. The greatest efficacy was ob-served in the BRCAm cohorts, regardless of gBRCAm/sBRCAm. For patients without a BRCAm, greater effi-cacy was observed in the HRD-positive than the HRD-negative cohorts. The safety profile was consistent with that established in previous olaparib studies.(c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

Automated summary

In this study, olaparib treatment demonstrated efficacy in patients with PSROC, showing effectiveness in not only BRCAm patients but also HRD-positive non-BRCAm patients, with a good safety profile.