Bevacizumab, atezolizumab and acetylsalicylic acid in recurrent, platinum-resistant ovarian cancer: the EORTC 1508-GCG phase II study
Mené sur 32 patientes atteintes d'un cancer de l'ovaire résistant aux sels de platine, cet essai randomisé multicentrique de phase II évalue l'efficacité, du point de vue de la survie sans progression à 6 mois, et la sécurité d'un traitement combinant bévacizumab, atézolizumab et aspirine
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.