Cohen EEW, et al. - Pembrolizumab and standard-of-care therapy were compared regarding their efficacy and safety for the treatment of head-and-neck squamous cell carcinoma. Outcomes of this randomized, open-label, phase 3 study suggest pembrolizumab to be associated with clinically meaningful prolongation of overall survival and favorable safety profile in patients with recurrent or metastatic head and neck squamous cell carcinoma. This supports the further evaluation of pembrolizumab as a monotherapy and as part of combination therapy in earlier stages of disease.

Methods

• At 97 medical centres in 20 countries, this randomized, open-label, phase 3 study was conducted.
• Using an interactive voice-response and integrated web-response system, researchers randomly assigned (1:1) patients with head-and-neck squamous cell carcinoma that progressed during or after platinum-containing treatment for recurrent or metastatic disease (or both), or whose disease recurred or progressed within 3–6 months of previous multimodal therapy containing platinum for locally advanced disease, in blocks of four per stratum to receive pembrolizumab 200 mg every 3 weeks intravenously or investigator's choice of standard doses of methotrexate, docetaxel, or cetuximab intravenously (standard-of-care group).
• Overall survival in the intention-to-treat population was assessed as the primary endpoint.
• They analyzed safety in the as-treated population.

Results

• Researchers randomly allocated 247 patients to pembrolizumab and 248 to standard of care between Dec 24, 2014, and May 13, 2016.
• As of May 15, 2017, 181 (73%) of 247 patients died in the pembrolizumab group compared to 207 (83%) of 248 patients in the standard-of-care group.
• In the intention-to-treat population, they noted median overall survival of 8·4 months (95% CI 6·4–9·4) with pembrolizumab and 6·9 months (5·9–8·0) with standard of care (hazard ratio 0·80, 0·65–0·98; nominal p=0·0161).
• Grade 3 or worse treatment-related adverse events were noted in fewer patients among those who were treated with pembrolizumab vs those with standard of care (33 [13%] of 246 vs 85 [36%] of 234).
• Pembrolizumab treated patients experienced hypothyroidism (in 33 [13%] patients) while standard of care receiving patients experienced fatigue (in 43 [18%]) as the most common treatment-related adverse event .
• Treatment-related death was reported for four patients treated with pembrolizumab (unspecified cause, large intestine perforation, malignant neoplasm progression, and Stevens-Johnson syndrome) and two patients treated with standard of care (malignant neoplasm progression and pneumonia).