Triplet maintenance (olaparib, pembrolizumab, and bevacizumab) in BRCA non-mutated patients with platinum-sensitive recurrent ovarian cancer: A multi-center, single-arm phase II study (OPEB-01).

Abstract

5584 Background: The optimal treatment of BRCA 1/2 non-mutated patients with platinum-sensitive recurrent ovarian cancer remains unknown. In this study, we evaluated the efficacy and safety of triplet maintenance therapy in BRCA non-mutated patients with platinum-sensitive recurrent ovarian cancer. Methods: BRCA 1/2 non-mutated patients with platinum-sensitive recurrent epithelial ovarian cancer, showing a complete/partial response after second-line platinum-based chemotherapy, were eligible. Triplet maintenance therapy (olaparib, bevacizumab, and pembrolizumab) was administered until disease progression or unacceptable toxicity. The primary endpoint was the progression-free survival (PFS) rate at six months after therapy initiation. The secondary endpoints were PFS, overall survival, and safety. The translational objectives included biomarker evaluation with respect to survival outcomes. Results: Forty-four patients were enrolled (median age 61 years), majority with high-grade serous carcinoma (93.2%) and partial response (75.0%) to second-line chemotherapy. Overall, 54.6% were homologous recombination deficiency (HRD)-positive (genomic instability score ≥ 42) and 63.6% had PD-L1 positive tumors (combined positive score [CPS] ≥ 1). At 6 months, the PFS rate was 88.6% (95% confidence interval [CI] 75.4–96.2). The median PFS has not been reached. The most common ≥ grade 3 treatment-related adverse events (AEs) were anemia (20.5%) and neutropenia (6.8%), but there were no grade 4 AEs. Exploratory analysis demonstrated remarkable survival outcomes regardless of HRD status, whereas patients with PD-L1 CPS ≥ 1 showed improved PFS compared to those with PD-L1 CPS < 1 ( P = 0·032). Analysis of molecular consensus subtype of the pre-treatment tissue samples showed that patients with mesenchymal subtype demonstrated poor PFS, compared to non-mesenchymal subtypes (p = 0.0023). Conclusions: This is the first report on triplet maintenance therapy in BRCA non-mutated platinum-sensitive recurrent ovarian cancer. The results show that the triplet maintenance therapy is efficacious with manageable toxicity, showing a particular promise for patients with molecular consensus subtype other than mesenchymal. Clinical trial information: NCT04361370 .