Research in context
Evidence before this study
We searched PubMed on April 11, 2018, using the terms “PD-1”, “PD-L1”, “MK-3475”, “lambrolizumab”, “pembrolizumab”, “Keytruda”, “BMS-936558”, “nivolumab”, “Opdivo”, “MPDL3280A”, “atezolizumab”, “Tecentriq”, “MEDI4736”, “durvalumab”, “Imfinzi”, “MSB0010718C”, “avelumab”, or “Bavencio” and “head and neck cancer”. We applied no time limits or language restrictions to the search. We also searched the abstracts for the 2016 and 2017 American Society of Clinical Oncology Annual Meeting and the 2016 and 2017 European Society for Medical Oncology Congress using the same search terms to identify results of any clinical trials that were not yet published in the peer-reviewed literature. We identified one randomised phase 3 trial of anti-programmed death 1 (PD-1) or anti-programmed death ligand 1 (PD-L1) monotherapy for squamous cell carcinoma of the head and neck—the CheckMate 141 study of nivolumab versus investigator's choice of docetaxel, methotrexate, or cetuximab for patients with recurrent or metastatic disease following platinum-based chemotherapy. Phase 1 and phase 2 studies of anti-PD-1 or anti-PD-L1 monotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck were identified, including the phase 1 KEYNOTE-012 and phase 2 KEYNOTE-055 studies of pembrolizumab, a phase 1 study of atezolizumab (NCT01375842), and the phase 2 HAWK study of durvalumab.
Added value of this study
To our knowledge, these data are the first published report of a randomised, controlled trial of pembrolizumab as therapy for recurrent or metastatic squamous cell carcinoma of the head and neck. Pembrolizumab provides a clinically meaningful prolongation of overall survival and has a favourable safety profile compared with standard-of-care therapy with methotrexate, docetaxel, or cetuximab. There was a clear relationship between higher PD-L1 expression and the benefit of pembrolizumab relative to standard-of-care therapy. Receipt of an immune checkpoint inhibitor by patients in the standard-of-care group appeared to decrease the treatment effect of pembrolizumab, a finding that has implications for future oncology studies, particularly those done in patients with cancer for which immune checkpoint inhibitors have received regulatory approval.
Implications of all the available evidence
Anti-PD-1 and anti-PD-L1 monotherapy have a favourable benefit-to-risk profile in patients with recurrent or metastatic squamous cell carcinoma of the head and neck that progress after platinum-based chemotherapy. The benefit of pembrolizumab monotherapy appears to be greater in patients whose tumours express PD-L1 than in patients whose tumours do not express the ligand. The survival benefit and safety profile of monotherapy with anti-PD-1 and anti-PD-L1 therapies in the recurrent or metastatic setting support the evaluation of monotherapy in earlier stages of disease and the evaluation of combination regimens that include PD-1 and PD-L1 inhibitors.