Olaparib safe, effective in ovarian cancer patients with BRCA mutation, HRD

Olaparib demonstrates clinical activity across patients with platinum-sensitive relapsed ovarian cancer and known BRCA mutation and homologous recombination deficiency (HRD), as shown in the phase II LIGHT study.

LIGHT included 272 ovarian cancer patients who received ≥1 prior line of platinum-based chemotherapy. Of these, 75 women had germline BRCA mutation (gBRCAm, cohort 1), 26 had somatic BRCA mutation (sBRCAm, cohort 2), 68 had HRD-positive tumours without BRCA mutation (cohort 3), 90 had HRD-negative tumours (cohort 4), and 13 had a failed or missing Myriad test result and thus were unable to be assigned to a cohort.

At baseline, the overall population had a median age of 66 years, with a median time from primary diagnosis of 32.4 months. A total of 194 patients (71.3 percent) had International Federation of Gynecology and Obstetrics (FIGO) stage III disease at diagnosis, and 181 (66.5 percent) had an Eastern Cooperative Oncology Group (ECOG) performance status of 0.

Of the enrolled patients, 271 and 270 were included in safety and efficacy analyses, respectively. At data cutoff (6 months after the last patient was enrolled), objective response rates were 69.3 percent in the gBRCAm cohort, 64.0 percent in the sBRCAm cohort, 29.4 percent in the HRD-positive cohort, and 10.1 percent in the HRD-negative cohort. The respective disease control rates were 96.0 percent, 100.0 percent, 79.4 percent, and 75.3 percent in each cohort.

Median progression free survival was 11.0 months in the gBRCAm cohort, 10.8 months in the sBRCAm cohort, 7.2 months in the HRD-positive cohort, and 5.4 months in the HRD-negative cohort.

Safety was consistent with that established in previous olaparib studies. Commonly reported treatment-emergent adverse events (≥20 percent) included nausea, fatigue/asthenia, vomiting, anaemia, constipation, diarrhoea, and decreased appetite. [J Clin Oncol 2020;38:1164-1174; Ann Oncol 2019;30:551-557]

The findings suggest that olaparib may represent an effective chemotherapy-sparing treatment for all patients with platinum-sensitive relapsed ovarian cancer.