Lynparib induces improvement in OS rate in platinum-sensitive germline/somatic BRCA+ recurrent ovarian cancer

Although efficacy was observed in all cohorts, treatment with olaparib was associated with the greatest overall survival (OS) benefit in patients with platinum-sensitive recurrent ovarian cancer harboring germline or somatic BRCA mutations, according to the final OS analysis of the LIGHT phase 2 study (NCT02983799).

Published results show that at a median follow-up of 26.3 months (range 0.6-36.9 months) in the efficacy analysis set (n=270) and the final data cutoff date in 2020, the germline BRCA mutation cohort (cohort 1; n=75), systemic BRCA mutation cohort (cohort 2; n=25), homologous recombination deficiency (HRD)-positive, non-BR The 18-month OS rates for the CA-mutated cohort (cohort 3; n=68) and the HRD-negative cohort (cohort 4; n=89) were 86.4% (95% CI, 76.2%-92.4%) and 88, respectively. .0% (95%CI, 67.3%-96.0%), 78.6% (95%CI, 66.6%-86.8%), and 59.6% (95%CI, 48.6%-68.9%). The 1-year OS rates of each cohort were 94.6% (95%CI, 86.3%-97.9%), 92.0% (95%CI71.6%-97.9%), 89.4% (95%CI-79.1%-94.8%), and 71.9% (95%CI/61.3%-80.1%), respectively.

Olaparib in platinum-sensitive recurrent ovarian cancerFinal OS analysis from the LIGHT study showed that the highest OS rate was observed in the germline/somatic BRCA mutation cohort. Among patients without BRCA mutations, the HRD-positive cohort had the highest OS rate. The open-label, non-randomized, non-controlled, multicenter LIGHT study prospectively evaluated the efficacy of olaparib in patients with platinum-sensitive recurrent ovarian cancer who received 1 or more platinum-based chemotherapy with known BRCA mutation status and HRD status.

Preliminary analysis results of the study show that the overall response rate (ORR) for cohorts 1, 2, 3, and 4 were 69.3% (95% CI, 57.6%-79. 5%), 64.0% (95%CI42.5%-82.0%), 29.4% (95%CI19.0%-41.7%) and 10.1% (95%CI24.7%-18.3%). The primary endpoint of clinical trial data is investigator-assessed ORR according to RECIST 1.1.2. Secondary endpoints are OS and safety. A similar pattern of relative benefit was observed between cohorts when patients were stratified by the number of prior chemotherapy regimens [1 versus 2 or more]. Compared with the preliminary analysis and the previous olaparib study, no new safety signals were observed in the final LIGHT OS analysis.

Data from the final analysis showed that the median total treatment time in the overall population was 7.4 months (range, 0.5-30.6). Notably, 29.5% of patients required dose interruption and 26.9% of patients required dose reduction; adverse reactions (AEs) resulted in dose interruption and dose reduction in 26.2% and 21.8% of patients, respectively. Treatment emergent adverse events (TEAEs) leading to treatment discontinuation occurred in 5.2% of patients. The most common TEAEs leading to discontinuation included fatigue/asthenia and nausea, each reported by 2 patients (0.7%).

The most common serious treatment-related adverse events of any grade included anemia (1.1%), pneumonia (0.7%), and abdominal pain (0.7%). Adverse events of particular concern included one patient (0.4%) who developed grade 2 pneumonitis 57 days after starting olaparib treatment and one patient who developed grade 2 pulmonary fibrosis 110 days after starting olaparib treatment. Grade 4 acute myeloid leukemia occurred in 1 patient 711 days after starting olaparib treatment (0.4%); however, this was not considered to be related to olaparib.

Adverse events resulted in 2 patient deaths (0.7%) but were not considered related to olaparib, including death from atrial fibrillation in the somatic BRCA mutation cohort 46 days after starting olaparib treatment, and death from intestinal perforation that occurred during the analysis of survival follow-up in the unallocated cohort.

Reference materials:https://www.onclive.com/view/olaparib-elicits-improved-os-rates-in-platinum-sensitive-germline-somatic-brca-relapsed-ovarian-cancer