In a cohort of a phase II trial reported in The Lancet Oncology, Assuntina G. Sacco, MD, and colleagues found that the combination of pembrolizumab and cetuximab produced durable responses in patients with recurrent or metastatic head and neck squamous cell carcinoma who had received no prior PD-1, PD-L1, or EGFR inhibitor treatment.

Assuntina G. Sacco, MD

Study Details

In the investigator-initiated U.S. multicenter trial, 33 patients (cohort 1) who had platinum-resistant disease or were platinum-ineligible were enrolled between March 2017 and July 2019. Patients received pembrolizumab at 200 mg every 3 weeks plus cetuximab at a loading dose of 400 mg/m² followed by 250 mg/m² weekly in 21-day cycles, with treatment continuing until disease progression or unacceptable toxicity.

The primary endpoint was overall response rate on Response Evaluation Criteria in Solid Tumors version 1.1 by 6 months in the intention-to-treat population. The trial comprises two additional cohorts including patients with previous response to immunotherapy followed by relapse or disease progression with or without previous cetuximab exposure and a cohort for cutaneous head and neck squamous cell carcinoma; findings will be reported separately after cohorts are fully accrued.

Responses

Median follow-up was 7.3 months (interquartile range = 3.9–10.9 months). By 6 months, objective responses (all partial) were observed in 15 patients (45%; 95% confidence interval [CI] = 28%–62%). An additional five patients (15%) had stable disease.

The median duration of response was 13.1 months (95% CI = 6.5 months–not reached). Conversion from stable disease to partial response at 6.1 months and then to complete response at 8.2 months was observed in one patient, yielding a response rate beyond the 6-month time point of 48%.

Objective response by 6 months was less common among human papillomavirus (HPV)-positive vs HPV-negative patients (3 of 12 = 25% vs 12 of 21 = 57%), although the difference was not significant (P = .18). No association between PD-L1 expression combined positive score (CPS) and objective response was observed (P = .80).

At the time of data cutoff (January 2020), median progression-free survival was 6.5 months (95% CI = 2.1 months–not reached) and median overall survival was 18.4 months (95% CI = 11.0 months–not reached). No association was observed between HPV status and overall (P = .30) or progression-free survival (P = .40) or between CPS and overall (P = .70) or progression-free survival (P = .40).   

Adverse Events

Patients experienced 13 grade 3 treatment-related adverse events and 1 grade 4 treatment-related adverse event (sepsis). The most common grade ≥ 3 treatment-related adverse events were oral mucositis (9%) and acneiform rash, hypomagnesemia, and colitis (6% each). Serious treatment-related adverse events consisted of colitis (6%), laryngeal edema (3%), acidosis (3%), and sepsis (3%). Treatment-related adverse events led to discontinuation of treatment in five patients (15%). There were no treatment-related deaths.

The investigators concluded: “Pembrolizumab combined with cetuximab shows promising clinical activity for recurrent or metastatic head and neck squamous cell carcinoma, and merits further investigation.”

Dr. Sacco, of Moores Comprehensive Cancer Center, University of California, San Diego, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Merck Sharp & Dohme. For full disclosures of the study authors, visit thelancet.com.