PD-L1 CPS Score Could Direct Treatment Decisions in Recurrent/Metastatic Head and Neck Cancer

Kevin Harrington, PhD

PD-L1 combined positive score (CPS) may serve to predict whether a patient with PD-L1–expressing recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) will receive optimal benefit with pembrolizumab (Keytruda) alone vs in combination with chemotherapy or with cetuximab (Erbitux) plus chemotherapy, according to an efficacy subgroup analysis of the phase 3 KEYNOTE-048 trial (NCT02358031).¹

Overall, 882 patients with recurrent or metastatic HNSCC and who had not received prior systematic therapy were enrolled in the trial. Among these participants, 128 had PD-L1 CPS less than 1 and 373 had a PD-L1 CPS between 1 and 19. Enrolled participants were randomized 1:1:1 to receive either single-agent pembrolizumab, pembrolizumab plus chemotherapy, or cetuximab plus chemotherapy.

An efficacy analysis of the PD-L1 CPS less than 1 and CPS 1 to 19 subgroups were performed post hoc.

The data, which were recently published in the Journal of Clinical Oncology, found that patients with a PD-L1 CPS less than 1 were more likely to experience superior overall survival (OS) when receiving cetuximab plus chemotherapy vs single-agent pembrolizumab. Here, the median OS was 7.9 months with pembrolizumab vs 11.3 months cetuximab/chemotherapy (HR, 1.51; 95% CI, 0.96-2.37). However, among patients with a PD-L1 CPS between 1 and 19, the median OS was 10.8 months with pembrolizumab vs 10.1 months with the cetuximab combination (HR, 0.86; 95% CI, 0.66-1.12).

Moreover, in a comparison of pembrolizumab/chemotherapy vs cetuximab/chemotherapy, patients with a PD-L1 CPS less than 1 had a median OS of 11.3 months vs 10.7 months (HR, 1.21; 95% CI, 0.76-1.94). However, for those with a PD-L1 CPS between 1 and 19, median OS was 12.7 months with pembrolizumab/chemotherapy vs 9.9 months with cetuximab/chemotherapy (HR, 0.71; 95% CI, 0.54-0.94).

These findings, suggest study authors, support previous findings of pembrolizumab benefit for patients with PD-L1–expressing HNSCC. However, they also suggest that PD-L1 CPS score can be an effective strategy for deciding which of the 3 treatment options will best benefit a patient with PD-L1–expressing HNSCC. Furthermore, while PD-L1 expression is a useful predictor of the immunotherapy’s efficacy, exploration into further predictive biomarkers for low PD-L1–expressing HNSCC is warranted.

“We have found that patients with head and neck cancer benefit from different approaches to treatment depending on the levels of a key immune protein in the tumor and among the surrounding cells,” lead study author Kevin Harrington, PhD, professor of biological cancer therapies at The Institute of Cancer Research, London, and consultant clinical oncologist at The Royal Marsden NHS Foundation Trust, said. “This new, more refined interpretation of the PD-L1 test should give clinicians a much clearer indication of which patients are most likely to benefit from immunotherapy alone and who should be considered for immunotherapy in combination with chemotherapy.”

Harrington added that the findings also indicate that patients with a moderate PD-L1 score would benefit from pembrolizumab plus chemotherapy as opposed to single-agent treatment, and that these new findings could potentially change the approach to caring for this patient population.

Researchers did acknowledge that the number of participants with a PD-L1 CPS less than 1 was small, and that future research efforts should seek to continue exploring the biomarker’s usefulness in low–expressing PD-L1. However, given that the PD-L1 test is affordable and reliable, the data suggest that it should be utilized to assess how best to incorporate pembrolizumab into this patient populations’ treatment plans.²

“Smarter tests to identify patients who are most likely to respond to treatment are a key aspect of precision medicine and are urgently needed for immunotherapies,” Kristian Helin, MSc, PhD, chief executive of The Institute of Cancer Research in London, said. “Tests like these can help improve outcomes for patients and make sure we don’t subject people who are unlikely to respond to treatments that won’t benefit them. I hope our new study can improve care for patients with head and neck cancer by helping to optimize treatment depending on test results.”

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 ahead of print March 25, 2022. doi:10.1200/JCO.21.02198.
2. Test can personalise use of immunotherapy and chemotherapy for head and neck cancer. The Institute of Cancer Research. News release. Accessed March 29, 2022. https://bit.ly/3NusPBC