Pembrolizumab plus chemotherapy showed increased efficacy with increasing PD-L1 expression in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) in a subgroup analysis of the phase 3 KEYNOTE-048 trial.1
Among patients with a PD-L1 combined positive score (CPS) of 1-19, pembrolizumab plus chemotherapy improved overall survival (OS), compared with cetuximab plus chemotherapy. However, among patients with a PD-L1 CPS below 1, there was no significant difference in OS between the treatment groups.
These findings were published in the Journal of Clinical Oncology.
The KEYNOTE-048 trial (ClinicalTrials.gov Identifier: NCT02358031) enrolled 882 patients with recurrent or metastatic HNSCC. Patients were randomly assigned to receive pembrolizumab alone (n=301), pembrolizumab plus chemotherapy (platinum and fluorouracil; n=281), or cetuximab plus chemotherapy (platinum and fluorouracil; n=300).
In a prior analysis, pembrolizumab monotherapy and pembrolizumab-chemotherapy significantly improved OS, compared with cetuximab-chemotherapy, in patients with a PD-L1 CPS of 20 or higher and in those with a CPS of 1 or higher.2
For the current analysis, researchers evaluated patients with a PD-L1 CPS below 1 (n=128) and those with a CPS of 1-19 (n=373).1
In the CPS 1-19 subgroup, both pembrolizumab alone and pembrolizumab-chemotherapy demonstrated antitumor activity. However, only patients treated with pembrolizumab-chemotherapy had superior OS compared with patients who received cetuximab-chemotherapy.
In the CPS 1-19 cohort, the median OS was 10.8 months in the pembrolizumab group (n=124) and 10.1 months in the cetuximab-chemotherapy group (n=133; hazard ratio [HR], 0.86; 95% CI, 0.66-1.12; P =.12827). The median OS was 12.7 months in the pembrolizumab-chemotherapy group (n=116) and 9.9 months in the cetuximab-chemotherapy group (n=125; HR, 0.71; 95% CI, 0.54-0.94; P =.00726).
In the cohort with CPS below 1, neither pembrolizumab nor pembrolizumab-chemotherapy improved OS compared with cetuximab-chemotherapy.
In the CPS below 1 cohort, the median OS was 7.9 months in the pembrolizumab-alone group (n=44) and 11.3 months in the cetuximab-chemotherapy group (n=45; HR, 1.51; 95% CI, 0.96-2.37; P =.96241). The median OS was 11.3 months in the pembrolizumab-chemotherapy group (n=39) and 10.7 months in the cetuximab-chemotherapy group (n=43; HR, 1.21; 95% CI, 0.76-1.94; P =.78932).
“Results from the PD-L1 CPS 1-19 subgroup support previous findings of treatment benefit with pembrolizumab monotherapy and pembrolizumab-chemotherapy in patients with PD-L1 CPS ≥1 tumors,” the researchers wrote. “Although PD-L1 expression is informative, exploration of additional predictive biomarkers is needed for low PD-L1-expressing HNSCC.”
Disclosures: This research was supported by Merck Sharp & Dohme Corp. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
- Burtness B, Rischin D, Greil R, et al. Pembrolizumab alone or with chemotherapy for recurrent/metastatic head and neck squamous cell carcinoma in KEYNOTE-048: Subgroup analysis by programmed death ligand-1 combined positive score. J Clin Oncol. Published online March 25, 2022. doi:10.1200/JCO.21.02198
- Burtness B, Harrington KJ, Greil R, et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): A randomised, open-label, phase 3 study. Lancet. 2019;394(10212):1915-1928. doi:10.1016/S0140-6736(19)32591-7
This article originally appeared on Cancer Therapy Advisor