Recurrent or metastatic head and neck squamous-cell carcinoma (SCC) is associated with a poor prognosis, and the treatment options are limited in this disease setting, highlighting the need for novel treatment strategies. Pembrolizumab is a humanized high-affinity antibody that exerts dual-ligand blockade of the immune checkpoint receptor programmed cell death-1 (PD-1). It has demonstrated robust antitumor activity and acceptable tolerability in several tumors, including melanoma and lung cancer. The KEYNOTE-012 study is an ongoing multicohort, open-label, phase 1b trial that is evaluating pembrolizumab 10 mg/kg every 2 weeks in recurrent or metastatic head and neck SCC (Chow L, et al. ESMO 2014: Abstract LBA 31). The primary efficacy end point was overall response rate (ORR).
Of the 104 patients with head and neck SCC screened for PD ligand 1 (PD-L1) expression, 81 (78%) were PD-L1–positive; 60 of these patients were enrolled in the trial. At a median follow-up of 10.2 months, the ORR was 19.6%, including 1 complete response; the duration of response ranged from 8+ to 41+ weeks (the median was not reached). Of the enrolled patients, 15 (25%) continue to receive pembrolizumab therapy.
In the overall population, the median progression-free survival (PFS) was 9.3 months, and the median overall survival (OS) was 12.6 months. Based on human papillomavirus (HPV) status, no difference in ORR was found between the HPV-positive and HPV-negative subsets (20% vs 19.4%); however, the HPV-positive subgroup showed longer PFS (17.2 vs 9.1 months) and OS (not reached vs 9.5 months) compared with the HPV-negative subgroup. PD-L1 expression positively correlated with ORR (P = .018), with an ORR of 50% achieved by the 12 patients with high PD-L1 expression.
Treatment-related adverse events of any grade occurred in 58% of patients, and grade 3 or 4 adverse events accounted for 17% of these. The most common treatment-related adverse events were fatigue (18%), pruritus (10%), and nausea (8%). Based on these results, it was concluded that pembrolizumab was well-tolerated and demonstrated particular antitumor activity in HPV-positive advanced head and neck SCC.
