Pembrolizumab Plus Cetuximab Demonstrate Promising Clinical Activity for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma


Data from a phase 2 clinical trial with pembrolizumab and cetuximab yielded promising clinical activity in patients with recurrent or metastatic head and neck squamous cell carcinoma.

Pembrolizumab (Keytruda) plus cetuximab (Erbitux) elicited promising responses in a population of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), according to the results of a phase 2 trial (NCT03082534) that were published in Lancet Oncology.

Findings from the trial identified a 6-month overall response rate of 45% (95% CI, 28%-62%), meeting the study’s primary end point. All reported responses were noted as being partial responses. Additionally, 15% of patients had stable disease (95% CI, 3%-27%) and 39% of patients had progressive disease (95% CI, 23%-56%) as a best response by 6 months.

“To our knowledge, this is the first study to evaluate PD-1 blockade with EGFR inhibition in recurrent or metastatic HNSCC,” wrote the investigators. “The combination of pembrolizumab with cetuximab resulted in impressive response rates, durable responses, and prolonged overall survival for participants with platinum-resistant or platinum-ineligible recurrent or metastatic HNSCC who did not previously receive PD-1 or EGFR inhibitors.”

Thirty-three patients were enrolled on the trial between March 22, 2017, and July 16, 2019, all of whom received at least 1 dose of pembrolizumab. The data cutoff point for the study’s primary analysis was January 22, 2020. Median follow-up duration was 7.3 months.

Eligible patients had platinum-resistant or platinum-ineligible, recurrent or metastatic HNSCC and were at least 18 years old with an ECOG performance status of 0 to1. Additionally, patients were required to have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and have received no prior immunotherapy or EGFR inhibitors. Patients included in the study received a 200 mg dose of pembrolizumab intravenously every 3 weeks, with an initial dose of cetuximab at 400 mg/m2 intravenously followed by 250 mg/m2 intravenously once weekly.

For patients with partial or complete responses (CRs), a median duration of response (DOR) of 13.1 months (95% CI, 6.5–not reached [NR]) was reported. Eight of the 16 patients who experienced a partial or CR experienced a progression event or died, with a median time to the first radiographical response of 2.0 months (range, 1.8-8.4).

The median time to progression was 8.9 months (95% CI, 4.0-NR) for patients with stable disease, 3 of whom had either a progression event or has died by 6 months. The overall disease control rate was 61% for this cohort of patients.

Additional findings indicated that patients experienced a median progression-free survival (PFS) of 6.5 months (95% CI, 2.1-NR) and median overall survival of 18.4 months (95% CI, 11.0-NR). Thirteen (39%) deaths were reported at data cutoff, 9 of which were due to disease and 4 were due to adverse effects (AEs) unrelated to the study treatment.

Thirty patients reported a total of 223 treatment-related AEs, including 14 grade 3 or higher treatment-related AEs. Serious treatment-related AEs included colitis (6%), laryngeal edema (3%), acidosis (3%), and sepsis (3%).

A main limitation of the study comes from the open-label, non-randomized design, which requires confirmation for the results in a randomized controlled trial with a larger sample size. Moreover, while the ORR was evaluated at 6 months, the investigative team explained that further responses occurred after that point.

“Given the promising clinical activity, further evaluation of pembrolizumab with cetuximab in a randomized phase 3 study compared with first-line standard therapies for recurrent or metastatic HNSCC is warranted,” the investigators concluded.


Sacco AG, Chen R, Worden FP, et al. Pembrolizumab plus cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma: an open-label, multi-arm, non-randomised, multicentre, phase 2 trial. Lancet Oncol. 2021;22(6):883-892. doi:10.1016/S1470-2045(21)00136-4

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