In a post hoc analysis of the KEYNOTE-048 trial reported in the Journal of Clinical Oncology, Barbara Burtness, MD, and colleagues found that survival results with pembrolizumab and pembrolizumab/chemotherapy vs cetuximab/chemotherapy in patients with recurrent or metastatic head and neck squamous cell carcinoma and a PD-L1 combined positive score (CPS) of 1 to 19 supported CPS as a predictive factor for benefit of pembrolizumab and pembrolizumab/chemotherapy.
The previously reported primary analyses from the trial showed that pembrolizumab alone significantly improved overall survival among patients with CPS ≥ 1 and CPS ≥ 20, with a nonsignificant improvement in the total population, and that pembrolizumab/chemotherapy significantly improved survival in the CPS ≥ 1, CPS ≥ 20, and total populations.
Barbara Burtness, MD
The trial supported the June 2019 approval of pembrolizumab in combination with platinum/fluorouracil chemotherapy for all patients in this setting, and pembrolizumab as a single agent in those patients with CPS ≥ 1.
In the trial, 882 patients with no prior systemic treatment for recurrent or metastaitc disease were randomly assigned 1:1:1 to receive pembrolizumab alone, pembrolizumab/chemotherapy, or cetuximab/chemotherapy, with chemotherapy consisting of platinum and fluorouracil. The current analysis assessed outcomes in the CPS < 1 and CPS 1 to 19 populations. The randomly assigned CPS < 1 population consisted of 44 patients in the pembrolizumab group, 39 in the pembrolizumab/chemotherapy group, and 45 in the cetuximab/chemotherapy group. The CPS 1 to 19 population consisted of 124 patients in the pembrolizumab group, 116 in the pembrolizumab/chemotherapy group, and 133 in the cetuximab/chemotherapy group. For the sake of comparison, the previously reported results in the CPS ≥ 20 population were shown (133 in pembrolizumab group, 126 in pembrolizumab/chemotherapy group, and 122 in the cetuximab/chemotherapy group). As noted by the investigators, random assignment to pembrolizumab/chemotherapy was halted temporarily during the trial; thus, the cetuximab/chemotherapy population for the comparison with pembrolizumab/chemotherapy includes only those patients randomly assigned to cetuximab/chemotherapy while pembrolizumab/chemotherapy enrollment was ongoing.
In the CPS ≥ 20 population, median overall survival was 14.8 months for patients in the pembrolizumab group vs 10.7 months in the cetuximab/chemotherapy group (hazard ratio [HR] = 0.58, 95% confidence interval [CI] = 0.44–0.78). Median overall survival was 14.7 months in the pembrolizumab/chemotherapy group vs 11.0 months in the cetuximab/chemotherapy group (n = 110; HR = 0.60, 95% CI = 0.45–0.82).
In the CPS < 1 population, median overall survival was 7.9 months in the pembrolizumab group vs 11.3 months in the cetuximab/chemotherapy group (HR = 1.51, 95% CI = 0.96–2.37). Median overall survival was 11.3 months in the pembrolizumab/chemotherapy group vs 10.7 months in the cetuximab/chemotherapy group (n = 43; HR = 1.21, 95% CI = 0.76–1.94).
In the CPS 1 to 19 population, median overall survival was 10.8 months in the pembrolizumab group vs 10.1 months in the cetuximab/chemotherapy group (HR = 0.86, 95% CI = 0.66–1.12). Median overall survival was 12.7 months in the pembrolizumab/chemotherapy group vs 9.9 months in the cetuximab/chemotherapy group (n = 125; HR = 0.71, 95% CI = 0.54–0.94).
The investigators concluded, “Increased efficacy of pembrolizumab or pembrolizumab/chemotherapy was observed with increasing PD-L1 expression. PD-L1 CPS < 1 subgroup analysis was limited by small participant numbers. Results from the PD-L1 CPS 1 to 19 subgroup support previous findings of treatment benefit with pembrolizumab monotherapy and pembrolizumab/chemotherapy in patients with PD-L1 CPS ≥ 1 tumors. Although PD-L1 expression is informative, exploration of additional predictive biomarkers is needed for low PD-L1–expressing head and neck squamous cell carcinoma.”
Disclosure: The study was funded by Merck Sharp & Dohme Corp, a subsidiary of Merck & Co Inc. For full disclosures of the study authors, visit ascopubs.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.