Pembrolizumab Is Active in Platinum- and Cetuximab-Refractory Head and Neck Cancer

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“Results from this study indicate that pembrolizumab is an active agent for a patient population with limited options.”
— Joshua Bauml, MD, and colleagues

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IN THE PHASE II KEYNOTE-055 trial, pembrolizumab (Keytruda) was found to produce durable responses in patients with platinum- and cetuximab (Erbitux)-refractory head and neck squamous cell carcinoma.1 Results of the trial were reported by Joshua Bauml, MD, of the University of Pennsylvania, Philadelphia, and colleagues in the Journal of Clinical Oncology. Pembrolizumab was approved in August 2016 for the treatment of recurrent or metastatic head and neck squamous cell carcinoma with disease progression on or after platinum-containing chemotherapy. 

Study Details 

THE STUDY ENROLLED 171 patients with recurrent/metastatic head and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx resistant to both platinum and cetuximab between October 2014 and September 2015. Concurrent platinum and cetuximab treatment was not required, but patients had to have progressive disease or recurrence within 6 months of the last dose of each therapy. 

Patients received pembrolizumab at 200 mg every 3 weeks. Imaging was performed every 6 to 9 weeks. The primary endpoints were overall response rate on central review and safety. 

Patients had a median age of 61 years; 81% were male; 89% were white; 98% had an Eastern Cooperative Oncology Group performance status of 0 or 1; 58% were past cigarette smokers and 35% were never smokers; 58% had their primary tumor in the oropharynx; the median number of prior systemic therapies was 2 (range = 1–6); prior curative treatments included radiotherapy and chemotherapy in 89%, surgery in 57%, and adjuvant chemotherapy in 21%; 76% had received ≥ 2 lines of treatment for recurrent/ metastatic disease; 49% had received concurrent platinum and cetuximab; 77% were human papillomavirus (HPV)-negative; and 82% were programmed cell death ligand 1 (PD-L1)–positive (≥ 1% combined tumor and inflammatory cells positive). 

Response Rate 

THE OVERALL RESPONSE rate was 16% (95% confidence interval [CI] = 11%–23%), with 1 complete response and 27 partial responses observed. Stable disease was observed in an additional 19% of patients. Reduction in target lesion size was observed in 50% of patients. 

The median response duration was 8 months (range = 2+ to 12+ months), with 75% of responses ongoing at the time of analysis. Response rates were 16% in HPV-positive patients and 15% in HPV-negative patients; they were 18% in PD-L1–positive patients and 12% in PD-L1–negative patients. Analysis by ≥ 50% (n = 48) vs < 50% (n = 118) cells positive for PD-L1 showed response rates of 27% vs 13%. 


  • Pembrolizumab produced a response rate of 16% in recurrent/metastatic head and neck cancer, with a median response duration of 8 months (range = 2+ to 12+ months).
  • Responses were observed irrespective of HPV or PD‑L1 status.

Outcomes in HPV and PD-L1 Subgroups 

MEDIAN PROGRESSION-FREE survival was 2.1 months, and median overall survival was 8 months. Progression-free survival at 6 months was 23% in all patients, 25% in HPV-positive patients, and 21% in HPV-negative patients. Overall survival at 6 months was 59% in all patients, 72% in HPV-positive patients, and 55% in HPV-negative patients. 

Progression-free survival at 6 months was 24% in PD-L1–positive patients (31% in those with ≥ 50% positive cells) and 20% in PD-L1–negative patients (20% in those with < 50% positive cells). Overall survival at 6 months was 59% in PD-L1–positive patients (60% in those with ≥ 50% positive cells) and 56% in PD-L1–negative patients (58% in those with < 50% positive cells). 

Adverse Events 

AT DATA CUTOFF, patients had received pembrolizumab for a median of 90 days. Treatment-related adverse events of any grade occurred in 64% of patients, with the most common being fatigue (18%), hypothyroidism (9%), nausea (6%), aspartate transaminase (AST) increase (6%), and diarrhea (6%). Treatment-related grade ≥ 3 adverse events occurred in 15%, with the most common being AST increase and anemia (2% each). 

The most common immune-mediated adverse events of any grade or causal attribution were hypothyroidism (16%), pneumonitis (4%), and hyperthyroidism (2%). Treatment was discontinued due to treatment-related adverse events in 4% of patients. One patient died from treatment-related pneumonitis. 

The investigators concluded: “[P]embrolizumab exhibited clinically significant antitumor activity and an acceptable safety profile in heavily pretreated [recurrent/metastatic head and neck squamous cell carcinoma] regardless of HPV status. Results from this study indicate that pembrolizumab is an active agent for a patient population with limited options. The robust clinical activity demonstrated in this trial confirms the activity of this class of agents and supports ongoing immunotherapy studies in head and neck cancer.” ■

DISCLOSURE: The study was supported by Merck & Co. For full disclosure of the study authors, visit 


1. Bauml J, Seiwert TY, Pfister DG, et al: Pembrolizumab for platinum- and cetuximab-refractory head and neck cancer: Results from a single-arm, phase II study. J Clin Oncol 35:1542-1549, 2017.

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