A D Colevas1, R Bahleda2, F Braiteh3, A Balmanoukian4, I Brana5, N G Chau6, I Sarkar7, L Molinero8, W Grossman9, F Kabbinavar10, M Fassò10, C O'Hear10, J Powderly11. 1. Department of Medicine, Stanford Cancer Institute, Stanford, USA. Electronic address: colevas@stanford.edu. 2. Drug Development Department, Gustave Roussy, Villejuif, France. 3. Comprehensive Cancer Centers of Nevada, University of Nevada Las Vegas School of Medicine, Las Vegas. 4. Medical Oncology Department, The Angeles Clinic, Los Angeles, USA. 5. Medical Oncology Department, Vall D'Hebron University Hospital, Barcelona, Spain. 6. Medical Oncology, Dana-Farber Cancer Institute Harvard Medical School, Boston. 7. Product Development Biostatistics, Genentech, Inc., South San Francisco. 8. Oncology Biomarker Development, Genentech, Inc., South San Francisco. 9. Pharmaceutical Development, Genentech, Inc., South San Francisco. 10. Product Development Oncology, Genentech, Inc., South San Francisco. 11. Carolina BioOncology Institute, Huntersville, USA.
Abstract
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 i.v. 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 three experiencing grade 3 TRAEs and one experiencing a grade 4 TRAE (per CTCAE v4.0). 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). Median 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 HNC. ClinicalTrials.gov number: NCT01375842.
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 i.v. 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 three experiencing grade 3 TRAEs and one experiencing a grade 4 TRAE (per CTCAE v4.0). 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). Median 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 HNC. ClinicalTrials.gov number: NCT01375842.
Authors: Hosam H Alkhatib; Christopher A Maroun; Neha Amin; Gangcai Zhu; Meytal Guller; Matthew E Herberg; Evan S Wu; Tanguy Y Seiwert; Lisa M Rooper; David W Eisele; Carole Fakhry; Drew Pardoll; Rajarsi Mandal Journal: JAMA Otolaryngol Head Neck Surg Date: 2022-06-01 Impact factor: 8.961
Authors: Yucai Wang; Shouhao Zhou; Fang Yang; Xinyue Qi; Xin Wang; Xiaoxiang Guan; Chan Shen; Narjust Duma; Jesus Vera Aguilera; Ashish Chintakuntlawar; Katharine A Price; Julian R Molina; Lance C Pagliaro; Thorvardur R Halfdanarson; Axel Grothey; Svetomir N Markovic; Grzegorz S Nowakowski; Stephen M Ansell; Michael L Wang Journal: JAMA Oncol Date: 2019-07-01 Impact factor: 31.777