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 et récidivant, cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression à 6 mois, et la toxicité d'un traitement combinant bévacizumab, atézolizumab et acide acétylsalicylique
Purpose: Treatment options for patients with 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 1/2 inhibitor aspirin [acetylsalicylic acid (ASA)] in PROC.
Patients and Methods: Patients were randomized to bev monotherapy 15 mg/kg (arm 1), atezo 1,200 mg plus placebo (pbo; arm 2), atezo 1,200 mg plus ASA 320 mg/daily (arm 3), bev 15 mg/kg plus atezo 1,200 mg plus pbo (arm 4), or bev 15 mg/kg plus atezo 1,200 mg plus ASA 320 mg/daily (arm 5). Primary endpoint was progression-free survival at 6 months (PFS-6) according to RECIST v1.1 assessed by a local investigator. Secondary objectives included overall survival, PFS, second PFS (PFS2), and tolerability. Time to first subsequent therapy (TFST) was evaluated in a post hoc analysis.
Results: In arms 1 (bev), 4 (bev–atezo–pbo), and 5 (bev–atezo–ASA), there were 7/32 [21.9%, 70% confidence interval (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 and response rates were 2.3 for bev monotherapy, 4.1 for bev–atezo–pbo, and 4.0 months for bev–atezo–ASA and 10%, 19%, and 15%, respectively. Two patients achieved an ongoing complete response lasting for more than 5 years from randomization (1 in bev–atezo–pbo and 1 in bev–atezo–ASA). A post hoc analysis of TFST suggested benefit of adding bev to atezo–ASA (P < 0.001). Tumor-infiltrating lymphocytes (TIL) increased in the atezo-containing arms after the first two cycles, and increased TIL were associated with a significantly longer TFST.
Conclusions: The addition of ASA to bev plus atezo was well-tolerated but did not improve efficacy in PROC. Relative to bev alone, the bev plus atezo combination numerically improved PFS. Exploratory translational analyses suggest clinical benefit in a subgroup of patients characterized by high TIL infiltration and PD-L1–positive tumors at baseline.
Clinical Cancer Research , résumé 2024