FDA Approves Keytruda® for Firstline Head and Neck Cancer

The U.S. Food and Drug Administration approved Keytruda® (pembrolizumab) for firstline treatment of patients with metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC).

The decision was based on results from the randomized, multicenter, three-arm, open-label, active-controlled KEYNOTE-048 that included 882 patients with metastatic HNSCC who had not previously received systemic therapy for metastatic disease or with recurrent disease who were considered incurable by local therapies.

Patients were randomized 1:1:1 to receive pembrolizumab as a single agent, pembrolizumab plus chemotherapy (carboplatin or cisplatin and fluorouracil), or cetuximab plus chemotherapy (carboplatin or cisplatin and fluorouracil). Patients were stratified by tumor PD-L1 expression, HPV status, and Eastern Cooperative Oncology Group performance status score.

Significantly improved overall survival with pembrolizumab

Patients receiving pembrolizumab plus chemotherapy had statistically significant improvement in overall survival (OS) compared with those receiving cetuximab plus chemotherapy: The median OS was 13.0 months and 10.7 months, respectively (hazard ratio [HR] = 0.77; 95% CI, 0.63-0.93; P=0.0067). The results were similar among a cohort of patients with a Combined Positive Score (CPS) ≥20 (HR=0.69; 95% CI, 0.51-0.94) and those with a CPS ≥1 (HR=0.71; 95% CI, 0.57-0.88).

The study also resulted in statistically significant improvements in OS for the subgroups of patients with PD‑L1 CPS ≥1 HNSCC and PD-L1 CPS ≥20 HNSCC who were randomized to receive pembrolizumab as a single agent compared with cetuximab plus chemotherapy. In the CPS ≥1 subgroup, the median OS was 12.3 months for the pembrolizumab arm and 10.3 months for the cetuximab plus chemotherapy arm (HR=0.78; 95% CI, 0.64-0.96; P=0.0171). For the CPS ≥20 subgroup, the median OS was 14.9 months for the pembrolizumab arm and 10.7 months for the cetuximab plus chemotherapy arm (HR=0.61; 95% CI, 0.45-0.83; P=0.0015). At the time of the interim analysis, there was no significant difference in OS between the pembrolizumab as a single agent arm and the cetuximab plus chemotherapy arm for the overall population.

There were no significant differences in progression-free survival among the different treatment cohorts.

The most common adverse events (AEs) reported in patients receiving pembrolizumab as a single agent were fatigue, constipation, and rash. The most common AEs reported in patients who received pembrolizumab in combination with chemotherapy were nausea, fatigue, constipation, vomiting, mucosal inflammation, diarrhea, decreased appetite, stomatitis, and cough.