Patients (pts) with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) have limited treatment options. The programmed death (PD)-1 pathway is a key mechanism by which tumors evade immune surveillance. Approximately 60% of oropharynx cancers are associated with HPV infection. It is hypothesized that virally induced tumors may have enhanced immunogenicity and PD-L1 expression. Pembrolizumab (pembro), an anti–PD-1 antibody, blocks interaction between PD-1 and PD-L1. This presentation will summarize the current phase 1b data for pembro in R/M HNSCC.
KEYNOTE-012 (NCT01848834) is a phase 1b study evaluating the efficacy and safety of pembro in pts with advanced solid tumors, including 2 R/M HNSCC cohorts. The initial (I) HNSCC cohort enrolled PD-L1+ pts; these pts received pembro 10 mg/kg Q2W. Additional HNSCC pts were enrolled, regardless of PD-L1 status, in an expansion (E) cohort to further explore pembro in a different dosing regimen (200 mg Q3W). HPV status was collected for all HNSCC pts. Imaging was performed every 8 wk to assess treatment response. The primary endpoint was overall response rate (ORR; RECIST v1.1), and a key secondary endpoint was response among HPV+ pts.
In total, 192 R/M HNSCC pts received pembro during this phase 1b trial (I=60 pts; E=132 pts). 32 pts were still on treatment at the data cutoff (Sept 1, 2015). The majority of pts (84%) received prior therapies for recurrent disease. ORR (confirmed) was 18% (95% CI, 13-24). 7 pts had a complete response; 27 pts had a partial response. By Sept 1, 2015, median duration of response was not yet reached (range, 2+ to 22+ mo); median follow-up duration for responders was 13 mo (range, 8-24). Responses were ongoing in 22 (76%) pts. ORR was 22% (95% CI, 13-34) in HPV+ pts and 16% (95% CI, 10-23) in HPV- pts. Median OS was 9 mo (95% CI, 7-11); 6-mo PFS rate was 25%. Treatment-related AEs (TRAEs) occurred in 64% of pts; 12% of pts had a grade 3-4 TRAE. No pts died because of a TRAE.
The robust antitumor activity observed during this phase 1b study suggests pembro at either dose tested (200 mg Q3W or 10 mg/kg Q2W) is an active treatment for R/M HNSCC regardless of HPV status. Ongoing studies to assess the clinical benefit of pembro in HPV+ and HPV- R/M HNSCC include KEYNOTE-055 (NCT02255097), a phase 2 trial of pembro after progression on platinum and cetuximab; KEYNOTE-040 (NCT02252042), a phase 3 trial of pembro vs standard of care (SOC) after platinum failure; and KEYNOTE-048 (NCT02358031), a phase 3 trial of first-line pembro or pembro+SOC vs SOC. Study outcomes may enable treatment optimization in pts with HPV+ and HPV- R/M HNSCC.