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.
Study Details
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.
Key Findings
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.”
Dr. Burtness, of Yale University School of Medicine and Yale Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
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.
