Pembrolizumab for Platinum- and Cetuximab-Refractory Head and Neck Cancer: Results From a Single-Arm, Phase II Study

Abstract

Purpose There are no approved treatments for recurrent/metastatic head and neck squamous cell carcinoma refractory to platinum and cetuximab. In the single-arm, phase II KEYNOTE-055 study, we evaluated pembrolizumab, an anti-programmed death 1 receptor antibody, in this platinum- and cetuximab-pretreated population with poor prognosis. Methods Eligibility stipulated disease progression within 6 months of platinum and cetuximab treatment. Patients received pembrolizumab 200 mg every 3 weeks. Imaging was performed every 6 to 9 weeks. Primary end points: overall response rate (Response Evaluation Criteria in Solid Tumors v1.1, central review) and safety. Efficacy was assessed in all dosed patients and in subgroups on the basis of programmed death ligand 1 (PD-L1) expression and human papillomavirus (HPV) status. Results Among 171 patients treated, 75% received two or more prior lines of therapy for metastatic disease, 82% were PD-L1 positive, and 22% were HPV positive. At the time of analysis, 109 patients (64%) experienced a treatment-related adverse event; 26 patients (15%) experienced a grade ≥ 3 event. Seven patients (4%) discontinued treatment, and one died of treatment-related adverse events. Overall response rate was 16% (95% CI, 11% to 23%), with a median duration of response of 8 months (range, 2+ to 12+ months); 75% of responses were ongoing at the time of analysis. Response rates were similar in all HPV and PD-L1 subgroups. Median progression-free survival was 2.1 months, and median overall survival was 8 months. Conclusion Pembrolizumab exhibited clinically meaningful antitumor activity and an acceptable safety profile in recurrent/metastatic head and neck squamous cell carcinoma previously treated with platinum and cetuximab.

Fig 1.

Patient disposition. *One patient died because of cardiac arrest (not treatment related) and one died because of pneumonitis (treatment related).

Fig 2.

Efficacy of pembrolizumab. (A) The best percentage change from baseline in target lesions (ie, difference in size of target lesions between baseline and postbaseline assessments divided by baseline target lesion size times 100) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by central imaging vendor review (n = 141). (B) Treatment exposure and response duration in patients with a confirmed complete or partial response per RECIST v1.1 by central imaging vendor review (n = 28). (C) Kaplan-Meier estimate of progression-free survival per RECIST v1.1 by central imaging vendor review. (D) Kaplan-Meier estimate of overall survival. HPV, human papillomavirus.

Fig 2.

Efficacy of pembrolizumab. (A) The best percentage change from baseline in target lesions (ie, difference in size of target lesions between baseline and postbaseline assessments divided by baseline target lesion size times 100) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by central imaging vendor review (n = 141). (B) Treatment exposure and response duration in patients with a confirmed complete or partial response per RECIST v1.1 by central imaging vendor review (n = 28). (C) Kaplan-Meier estimate of progression-free survival per RECIST v1.1 by central imaging vendor review. (D) Kaplan-Meier estimate of overall survival. HPV, human papillomavirus.

Fig A1.

Duration of response in patients with confirmed response per Response Evaluation Criteria in Solid Tumors, version 1.1, by central imaging vendor review (n = 28).

Fig A2.

Kaplan-Meier estimates of (A) progression-free survival and (B) overall survival by programmed death ligand 1 (PD-L1) status.