Bevacizumab, atezolizumab and acetylsalicylic acid in recurrent, platinum-resistant ovarian cancer: the EORTC 1508-GCG phase II study

Abstract Purpose: Treatment options for platinum-resistant ovarian cancer (PROC) are limited and new therapeutic strategies are urgently needed. This phase II, randomized, multicentre trial evaluated the safety and activity of the anti-PD-L1 antibody atezolizumab (atezo) combined with the VEGF-inhibitor bevacizumab (bev) and the irreversible cyclooxygenase inhibitor aspirin (ASA) in PROC. Patients and Methods: Patients were randomized to bev monotherapy 15 mg/kg (arm 1), atezo 1200 mg plus placebo (pbo)(arm 2), atezo plus ASA 320 mg/daily (arm 3), bev plus atezo plus pbo (arm 4) or bev plus atezo plus ASA (arm 5). Primary endpoint was progression-free survival at 6 months (PFS-6). Secondary objectives included overall survival (OS), PFS, PFS2 and tolerability. Time to first subsequent therapy (TFST) was evaluated in a post-hoc analysis. Results: In arms 1, 4 and 5, there were 7/32 (21.9%, 70% CI, 14.0-32.0), 8/32 (25.0%, 70% CI, 16.6-35.3), and 8/32 (25.0%, 70% CI, 16.6-35.3) patients alive and progression-free at 6 months. The primary objective was not reached in any arm. Median PFS were 2.3 for bev monotherapy, 4.1 for bev-atezo-pbo, and 4.0 months for bev-atezo-ASA. TFST suggested benefit of adding bev to atezo-ASA (p<0.001). Tumour-infiltrating lymphocytes (TILs) increased in the atezo containing arms and increased TILs were associated with longer TFST. Conclusions: The addition of ASA to bev-atezo was well tolerated but did not improve efficacy in PROC. Relative to bev, the bev-atezo combination numerically improved PFS. Exploratory analyses suggest clinical benefit in a subgroup of patients characterised by high TILs infiltration and PD-L1+ tumours at baseline.