The first trial to evaluate anti–­programmed cell death protein 1 (PD-1) blockade combined with epidermal growth factor receptor (EGFR) inhibition in head and neck squamous cell carcinoma demonstrates promising activity of the drug combination in patients with platinum-refractory or -ineligible disease, according to data presented at the 2020 Multidisciplinary Head and Neck Cancers Symposium.¹

Results of the phase II trial showed a 45% overall response rate and durable responses in patients treated with pembrolizumab and cetuximab. With a median follow-up of 7.6 months, patients with a complete or partial response had a median duration of response of 14.9 months, whereas those with stable disease had a median duration of response of 9.5 months. The median overall survival was 18.4 months.

“Ongoing and future studies are certainly indicated to look at combined anti–PD-1 and EGFR inhibition.”

— Assuntina G. Sacco, MD

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“These data suggest that pembrolizumab plus cetuximab may have promising activity for platinum-refractory or -ineligible patients with recurrent or metastatic head and neck squamous cell carcinoma,” said Assuntina G. Sacco, MD, Associate Professor of Medicine and Medical Director of Infusion Services at UC San Diego Moores Cancer Center, La Jolla, California. “The safety profile was also acceptable, resulting in few treatment-related discontinuations. Ongoing and future studies of combined anti–PD-1 and EGFR inhibition are indicated.”

As Dr. Sacco reported, it is well established that patients with recurrent or metastatic head and neck squamous cell carcinoma who are either platinum-refractory or -ineligible have poor survival outcomes. Although there are U.S. Food and Drug Administration–approved therapies in the second-line setting, including both checkpoint inhibitors (pembrolizumab and nivolumab) and an EGFR inhibitor (cetuximab), she added, these agents are approved only as monotherapies.

Study Details

For this trial, Dr. Sacco and colleagues enrolled platinum-refractory or -ineligible patients with recurrent or metastatic head and neck squamous cell carcinoma. Patients were required to have a good performance status, measurable disease, and adequate organ function. They also had to be naive to immunotherapy. Some patients were allowed to have received prior cetuximab, but only if it was provided in the curative-intent setting, said Dr. Sacco.

All patients received standard dosing of pembrolizumab every 3 weeks in addition to weekly cetuximab. The investigators performed response assessments with diagnostic imaging every 9 weeks. The study’s primary endpoint was overall response rate, defined as partial or complete responses per Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary endpoints included 12-month progression-free survival probability, overall survival, response duration, safety, and correlative analyses.

Study Findings

Previously reported safety and interim futility analyses demonstrated acceptable toxicity and met protocol specifications for trial continuation. At the 2020 Multidisciplinary Head and Neck Cancers Symposium, Dr. Sacco presented the updated analysis of cohort 1, which included anti–PD-1/programmed cell death ligand 1 (PD-L1) and cetuximab-naive patients. The investigators enrolled 33 patients (median age, 61) over a 2-year period, and the overwhelming majority had oral cavity primaries. The majority of patients had not received any prior therapy in the recurrent/metastatic setting.

The results showed 15 responders, including 1 complete response and 14 partial responses, for an overall response rate of 45%. The disease control rate in this cohort was approximately 61%.

Regarding the time to response, Dr. Sacco observed that the best responses often occurred early, which is similar to other immunotherapy trials. “The responses that occurred early were deep and sustained,” commented Dr. Sacco. “However, one patient on trial started out with a stable disease response that then turned into a partial response by about 4 months and then a complete response at 8 months. She has remained in complete response.”

Patients with complete or partial responses had a median duration of response of 14.9 months. Patients with stable disease had a median duration of response of 9.5 months. The median overall survival was 18.4 months.

There were three grade 3 treatment-related toxicities that were possibly attributed to both study drugs. Two of these patients discontinued cetuximab and had symptomatic improvement, whereas the third patient with grade 3 colitis discontinued treatment with both drugs. 

DISCLOSURE: Dr. Sacco has received research grants from Merck and Pfizer.

REFERENCE

1. Sacco AG, Chen R, Ghosh D, et al: An open-label, non-randomized, multi-arm, phase II trial evaluating pembrolizumab combined with cetuximab in patients with recurrent/metastatic head and neck squamous cell carcinoma: Updated results of cohort 1 analysis. 2020 Multidisciplinary Head and Neck Cancers Symposium. Abstract 15. Presented February 28, 2020.