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


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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.

References

1. 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

2. 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