New first-line treatment for recurrent or metastatic squamous cell carcinoma of head and neck: does one size fit all?

According to cancer statistics for 2012 (GLOBOCAN), the global incidence of HNC in that year stood at around 680,000, with 390,000 of these cases occurring in Asian countries. Around 240,000 Asian people died from HNC, accounting for 5.5% of global cancer deaths (1). Patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) have a poor prognosis. Treatment goals are limited, but include prolongation of survival, palliation of existing symptoms and prevention of new cancer-related symptoms. In particular, systemic chemotherapy has only a modest impact on outcome in these patients (2), and median survival in reported Phase III randomized trials ranges from 6 to 9 months (3-8). Platinum-based chemotherapy remains the standard, and although combination therapy has shown higher response rates, no other regimen has demonstrated a survival advantage over cisplatin monotherapy. In their randomized Phase III trial of cisplatin or carboplatin plus 5-FU (PF/CF) with or without cetuximab against PF/ CF for R/M SCCHN (EXTREME Study), Vermorken et al. reported that the hazard ratio for overall survival (OS) of PF/CF plus cetuximab to PF/CF alone was 0.80 [95% confidence interval (CI), 0.64–0.99]. Median OS was 10.1 months for PF/CF plus cetuximab versus 7.4 months for PF/CF alone (P=0.04) (9). From this result, PF/CF + cetuximab, the so-called EXTREME regimen, has been the standard first line chemotherapy for patients with R/ M SCCHN. For platinum-refractory R/M SCCHN, the anti-PD-1 antibodies nivolumab and pembrolizumab demonstrated a survival benefit in the pivotal Phase III trials (CheckMate141, KEYNOTE-040) (10,11). Recently, however, Burtness et al. reported the practicechanging results of a Phase III trial (KEYNOTE-048; KN-048) which compared the EXTREME regimen with pembrolizumab alone or PF/CF plus pembrolizumab for patients with previously untreated R/M SCCHN (12).