Isabelle Ray-Coquard, Marie-Christine Kaminsky-Forrett, Ryotaro Ohkuma, Aymeric de Montfort, Florence Joly, Isabelle Treilleux, Sarah Ghamry-Barrin, Diana Bello-Roufai, Pierre Saintigny, Antoine Angelergues, Lucas Michon, Anne-Claire Hardy-Bessard, Valéry Attignon, Jessie Auclair, Gabriel Chemin, Alexandra Lainé, Hélène Péré, David Veyer, Aude-Marie Savoye, Justine Berthet, Christophe Caux, Fabrice Lecuru, Bertrand Dubois, Sarah Bétrian
Combining immunotherapy with chemoradiation is effective in locally advanced cervical cancer. However, the impact of induction combination immunotherapy on immune modulation and treatment response is poorly understood. In this phase II trial (NCT04256213), 40 females with locally advanced cervical carcinoma received one cycle of nivolumab-plus-ipilimumab immunotherapy before standard chemoradiation, followed by maintenance nivolumab. We show, using multiplex-immunofluorescence tissue imaging, a significantly increased CD8+/FOXP3+ cell ratio (primary endpoint; increase of 0.87 cells/mm², P = 0.0164) and proliferative CD8+ T-cell density after one cycle of combination immunotherapy. HOT score (27-gene-based signature identifying immunologically active tumors) also increased significantly (exploratory analysis; 0.17, P < 0.0001). Objective response rates (secondary endpoint) were 13% immediately after combination immunotherapy, 98% (65% complete response) after chemoradiation, and 90% at treatment completion. High HOT score at baseline and immune changes induced by combination immunotherapy were associated with complete response at treatment completion. Induction immunotherapy may prime tumors for improved response to standard therapy. Pre-treatment dual immune checkpoint blockade in cervical cancer remains understudied. In this trial, the authors show that neoadjuvant immune checkpoint blockade enhances immune activation and correlates with improved response to subsequent chemoradiation in patients with cervical carcinoma.