Intermittent olaparib with neoadjuvant platinum-based chemotherapy in BRCA-mutated un-resectable ovarian cancer: the...

Maintenance therapy with poly(adenosine diphosphate-ribose) polymerase inhibitors following first-line platinum-based chemotherapy has improved survival outcomes in patients with BRCA-mutated advanced epithelial ovarian cancer. Although pre-clinical data support a synergistic interaction between poly(adenosine diphosphate-ribose) polymerase inhibitors and platinum agents, the clinical value of their concurrent administration in the neoadjuvant setting remains unclear. This study evaluated the feasibility and efficacy of adding olaparib to neoadjuvant chemotherapy in patients with newly diagnosed BRCA-mutated advanced epithelial ovarian cancer.

This open-label, single-arm phase II study (NCT04261465) enrolled 36 patients with newly diagnosed BRCA-mutated advanced epithelial ovarian cancer. Patients received three cycles of neoadjuvant chemotherapy with weekly carboplatin (area under the curve 2) and paclitaxel (60 mg/m² on days 1, 8, and 15 of a 28-day cycle), administered concurrently with intermittent oral olaparib 150 mg twice daily (300 mg/d) on days 1 to 3, 8 to 10, 15 to 17, and 22 to 24. The primary end point was complete pathological response at interval debulking surgery with ≥5 complete pathological responses among 35 patients required for the study to be considered positive. Secondary end points included objective response rate, progression-free survival, overall survival, and safety.

Among 35 patients who received at least two cycles of neoadjuvant therapy, complete pathological response was achieved in three patients (8.6%). The overall response rate was 89%, assessed at the completion of neoadjuvant treatment prior to interval debulking surgery. At a median follow-up of 42.9 months, median progression-free survival was 39.7 months (95% confidence interval 22.4 to not reached), while median overall survival was not reached (95% confidence interval 47.6 to not reached). Treatment-related adverse events occurred in 86% of patients. Dose reductions were required in 58%, and treatment discontinuation occurred in 11% of patients.

Concurrent administration of olaparib with platinum-based neoadjuvant chemotherapy did not increase complete pathological response. These findings suggest that the benefit of poly(adenosine diphosphate-ribose) polymerase inhibitors in BRCA-mutated advanced epithelial ovarian cancer may be driven mainly by post-chemotherapy maintenance rather than concurrent neoadjuvant use.