Safety and Clinical Activity of Atezolizumab in Head and Neck Cancer: Results From a Phase I Trial. Annals of oncology : official journal of the European Society for Medical Oncology Colevas, A. D., Bahleda, R., Braiteh, F., Balmanoukian, A., Brana, I., Chau, N. G., Sarkar, I., Molinero, L., Grossman, W., Kabbinavar, F., Fasso, M., O'Hear, C., Powderly, J. 2018


Background: Head and neck cancer (HNC) has a poor prognosis at advanced stages. Given the immunosuppressive tumor microenvironment in HNC, inhibition of the programmed death-ligand 1/programmed death-1 (PD-L1/PD-1) signaling pathway represents a promising therapeutic approach. Atezolizumab (anti-PD-L1) is efficacious against many tumor types. Here we report the clinical safety and activity from the HNC cohort of the phase Ia PCD4989g clinical trial.Patients and methods: Patients with previously-treated, advanced HNC received atezolizumab intravenously every 3 weeks for 16 cycles, up to 1 year or until loss of clinical benefit. Patients were monitored for safety and tolerability, and evaluated for response at least every 6 weeks. Baseline PD-L1 expression level and human papillomavirus (HPV) status were evaluated.Results: Thirty-two patients were enrolled; 7 patients (22%) had a primary tumor in the oral cavity, 18 (56%) in the oropharynx, 1 (3%) in the hypopharynx, 2 (6%) in the larynx, and 4 (13%) in the nasopharynx. Seventeen patients (53%) had =2 prior lines of therapy. Twenty-one patients (66%) experienced a treatment-related adverse event (TRAE), with 3 experiencing grade 3 TRAEs and 1 experiencing a grade 4 TRAE. No grade 5 TRAEs were reported. Objective responses by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1) occurred in 22% of patients, with a median duration of response of 7.4 months (range 2.8-45.8 months). Progression-free survival was 2.6 months (range 0.5-48.4 months), and median overall survival was 6.0 months (range 0.5-51.6+ months). Responses showed no association with HPV status or PD-L1 expression level.Conclusions: In this heavily pre-treated advanced HNC cohort, atezolizumab had a tolerable safety profile and encouraging activity, with responses observed regardless of HPV status and PD-L1 expression level. These findings warrant further investigation of atezolizumab in number: NCT01375842.

View details for DOI 10.1093/annonc/mdy411

View details for PubMedID 30219915