Final Overall Survival Results from the LIGHT Study of Olaparib Treatment in Platinum-Sensitive Relapsed Ovarian Cancer by BRCA Mutation and Homologous Recombination Deficiency Status

2021 Year in Review - Ovarian Cancer

The final overall survival analysis of the phase 2 LIGHT study indicates that olaparib therapy in patients with platinum-sensitive relapsed ovarian cancer provides overall survival benefit across patient cohorts, regardless of BRCA mutation and homologous recombination deficiency status, with a safety profile consistent with that previously described.

The open-label, nonrandomized, multicenter, phase 2 LIGHT study (NCT02983799) prospectively evaluated olaparib therapy in patients with platinum-sensitive relapsed ovarian cancer with known BRCA mutation (BRCAm) and homologous recombination deficiency (HRD) status. The results of the final overall survival (OS) analyses were presented at the 2021 American Society of Clinical Oncology Annual Meeting.

The LIGHT study enrolled patients with platinum-sensitive relapsed ovarian cancer, who had received ≥1 previous lines of platinum-based chemotherapy. Eligible patients were assigned to 1 of 4 cohorts based on their Myriad test results: germline BRCAm (cohort 1); somatic BRCAm (cohort 2); HRD-positive (non-BRCAm; cohort 3); and HRD-negative (cohort 4). All eligible patients received olaparib (starting dose 300 mg twice a day) until disease progression or unacceptable toxicity. OS was a secondary end point, which was analyzed at 12 months after the primary analysis and at 18 months after the last patient was enrolled. The data cutoff date was August 27, 2020.

Of the 271 patients who received olaparib, 270 had measurable disease at baseline and were evaluable for efficacy. At a median follow-up of 26.3 months, 18-month OS rates ranged from 59.6% to 88% (cohort 1: 86%; cohort 2: 88%; cohort 3: 79%; cohort 4: 60%), with the highest OS rates observed in the patients with BRCAm regardless of germline or somatic BRCAm status. Among patients without a BRCAm, higher OS rates were observed in patients with HRD-positive status. After olaparib discontinuation, the most frequent first subsequent treatment was platinum-based chemotherapy (39%). The median duration of treatment was 7.4 months.

Final safety analyses did not reveal the emergence of any new safety signal compared with the primary analysis or with previous olaparib studies. Serious treatment-emergent adverse events (TEAEs) occurred in 25% of patients; the most frequent serious TEAE was small intestinal obstruction (5.5%). TEAEs leading to treatment discontinuation were reported in 5% of patients. Three adverse events of special interest, which were caused by acute myeloid leukemia (post discontinuation), pneumonitis, and pulmonary fibrosis, were reported in 1 patient each.

The final OS analysis of the LIGHT study indicates that olaparib therapy in patients with platinum-sensitive relapsed ovarian cancer provides OS benefit across patient cohorts, regardless of BRCAm or HRD status, with a safety profile consistent with that previously described.

Source: Mathews CA, Simpkins F, Cadoo KA, et al. Olaparib treatment (Tx) in patients (pts) with platinum-sensitive relapsed ovarian cancer (PSR OC) by BRCA mutation (BRCAm) and homologous recombination deficiency (HRD) status: overall survival (OS) results from the phase II LIGHT study. J Clin Oncol. 2021;39(suppl_15). Abstract 5515.

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