Abstract
AbstractSince the initial reports of activity of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), investigation of the role of immune therapies has been the major focus of clinical trials in R/M HNSCC. Randomised trials initially with nivolumab and later with pembrolizumab established overall survival benefit in patients with R/M HNSCC previously treated with platinum compared to physicians choice of 2nd line therapy, and have led to regulatory approval around the world. More recently the Keynote-048 trial has compared both pembrolizumab monotherapy and pembrolizumab + platinum/5FU to the Extreme regimen of platinum/5FU/cetuximab in the first-line R/M setting. The key findings from this trial are that pembrolizumab monotherapy compared to Extreme improved overall survival in patients with PD-L1 combined positive score (CPS) ≥ 20 and ≥ 1, and that pembro/chemotherapy improved OS in CPS ≥ 20, CPS ≥ 1 and the total population. Relative to Extreme there was less toxicity in the monotherapy arm and comparable toxicity in the pembro/chemo arm. Based on this trial use of pembrolizumab as part of first-line treatment for R/M HNSCC is appropriate for the majority of patients, and represents a new standard of care. The focus has now moved to identifying combinations that may be superior to pembrolizumab monotherapy or to chemotherapy + pembrolizumab. Some of the more promising approaches under investigation in HNSCC are discussed in this chapter. In summary, immune therapies are now the cornerstone of management of R/M HNSCC with the approval of pembrolizumab in the first-line R/M setting.
Highlights
Prior to the Emergence of Immune TherapiesIt is over 30 years since single agent cisplatin was demonstrated to be active in recurrent/metastatic mucosal head and neck squamous cell carcinoma (R/M HNSCC) with trials suggesting improved survival [1, 2]
The Keynote-048 trial evaluated the role of pembrolizumab alone (200 mg 3 weekly) or in combination with platinum-5-FU chemotherapy compared to the standard of care, the Extreme regimen of platinum, 5FU and cetuximab [12]
In the combined positive score (CPS) ≥ 20 population the HR was 0.61 (95%CI 0.45–0.83, p = 0.0007), with medians of 14.9 versus 10.7 months and 2 year survival rates of 38.3% versus 22.1%
Summary
It is over 30 years since single agent cisplatin was demonstrated to be active in recurrent/metastatic mucosal head and neck squamous cell carcinoma (R/M HNSCC) with trials suggesting improved survival [1, 2]. The Extreme trial was a significant advance with the addition of the anti-EGFR monoclonal antibody, cetuximab to platinum and 5-Fluorouracil improving overall survival compared to chemotherapy alone [5]. The median overall survival improved from 7.4 months in the chemotherapy-alone arm to 10.1 months in the arm that received chemotherapy plus cetuximab (hazard ratio, 0.80; 95% confidence interval, 0.64 to 0.99; P = 0.04). Based on these results, the Extreme regimen was approved in many jurisdictions and became the standard of care for first-line treatment of R/M HNSCC. No treatment had been shown to improve survival in the second-line or beyond R/M HNSCC setting. The first major report in R/M HNSCC was at the Annual Meeting of the American Society of
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
