In an analysis of the KEYNOTE-048 trial reported in a research letter in JAMA Oncology, Yu et al identified outcomes with pembrolizumab alone or combined with chemotherapy vs cetuximab plus chemotherapy in patients with recurrent or metastatic head and neck squamous cell carcinoma with a low or intermediate PD-L1 combined positive score (CPS).
As noted by the investigators, KEYNOTE-048 established the benefit of treatment with pembrolizumab monotherapy and pembrolizumab plus chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma. They stated, “The authors reported overall survival analyses for the total population, those with a CPS of 20 or greater, and those with a CPS of 1 or greater, but to our knowledge, data on outcomes for patients with an intermediate (1–19) or low (< 1) CPS have not been previously published…. Combined, these subsets represented 57% of the KEYNOTE-048 study population.”
Study Details
The study included analysis of individual patient data for overall survival for 124 patients in the pembrolizumab monotherapy group, 116 in the pembrolizumab plus chemotherapy group, and 133 in the cetuximab plus chemotherapy group with a CPS of 1 to 19, and for 44, 39, and 45 patients, respectively, with a CPS of < 1. Analysis of progression-free survival included 124, 116, and 125 patients, respectively, with a CPS of 1 to 19, and 44, 40, and 45, respectively, with a CPS of < 1.
Key Findings
Overall, CPS was associated with overall survival among patients receiving pembrolizumab monotherapy and pembrolizumab plus chemotherapy, but not among those receiving cetuximab plus chemotherapy.
Among patients with a CPS of 1 to 19, compared with cetuximab plus chemotherapy, overall survival was significantly improved with pembrolizumab plus chemotherapy (hazard ratio [HR] = 0.69, 95% confidence interval [CI] = 0.52–0.91, P = .01), whereas improvement with pembrolizumab monotherapy was not significant (HR = 0.86, 95% CI = 0.66–1.12, P = .25). Among patients with a CPS of < 1, no improvement in overall survival was observed for pembrolizumab plus chemotherapy (HR = 1.13, 95% CI = 0.71–1.80, P = .60) or pembrolizumab monotherapy (HR = 1.4, 95% CI = 0.89–2.20, P = .14) vs cetuximab plus chemotherapy.
Among patients with a CPS of 1 to 19, compared with cetuximab plus chemotherapy, progression-free survival was not significantly improved with pembrolizumab plus chemotherapy (HR = 0.92, 95% CI = 0.71–1.19, P = .51) and was significantly poorer with pembrolizumab monotherapy (HR = 1.55, 95% CI = 1.20–2.00, P = .001). Among patients with a CPS of < 1, progression-free survival was numerically poorer with pembrolizumab plus chemotherapy (HR = 1.42, 95% CI = 0.91–2.23, P = .12) and significantly poorer with pembrolizumab monotherapy (HR = 2.17, 95% CI = 1.38–3.42, P = .001) vs cetuximab plus chemotherapy.
The investigators stated, “The results of this secondary analysis of KEYNOTE-048 suggest that CPS was associated with overall survival for treatment with pembrolizumab plus chemotherapy and pembrolizumab monotherapy but is not a general prognostic factor for patients with recurrent or metastatic head and neck squamous cell carcinoma. For patients with intermediate CPS, treatment with pembrolizumab plus chemotherapy but not pembrolizumab monotherapy was associated with improved overall survival vs treatment with cetuximab plus chemotherapy. For patients with low CPS, treatment with pembrolizumab monotherapy was associated with shorter progression-free survival and a trend toward shorter overall survival, while patients treated with pembrolizumab plus chemotherapy had similar progression-free and overall survival when both regimens were compared with treatment with cetuximab plus chemotherapy…. This analysis potentially provides a granular perspective that is relevant for many patients.”
Nancy Y. Lee, MD, of the Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, is the corresponding author for the JAMA Oncology article.
