Mehra Details the Importance of PD-L1 Expression in HNSCC Treatment Selection


Ranee Mehra, MD, discusses the link between PD-L1 expression and increased immunotherapy efficacy in head and neck squamous cell carcinoma, and what future treatment options may look like for patients in this space.

Immunotherapy (IO) has revolutionized the head and neck squamous cell carcinoma (HNSCC) space, but there are still avenues to explore to offer benefit to all patients, according to Ranee Mehra, MD.

In a presentation at the 40th Annual CFS®, Mehra, who is director of head and neck medical oncology and professor of medicine at the Marlene and Stewart Greenebaum Comprehensive Cancer Center, reviewed data from KEYNOTE-048 (NCT02358031) in HNSCC highlighting that PD-L1 positive patients have better outcomes with IO therapy of pembrolizumab (Keytruda), as either monotherapy, or with chemotherapy. She also touched on new data for IO in combination with radiation, which has not been as effective as investigators had hoped.

In an interview with Oncology Nursing News® following the presentation, Mehra recounted the main takeaways from her talk—underscoring the advantages and limitations of IO therapy in HNSCC, and where the field is continuing to focus.

“[Data from KEYNOTE-048 have] completely changed the course of the disease for patients,” Mehra said, adding that although not all patients derive benefit, clinicians are seeing more patients living longer with a good quality of life and without excessive toxicity. Moving forward, the field needs better biomarkers for monotherapy selection and better combination data, both upfront and in the refractory setting.

Interestingly, there may be opportunities in combining targeted therapies and IO therapies; however, these avenues have not been adequately explored, she noted. There has been interest in combining IO with targeted therapy and kinase inhibitors, such as lenvatinib (Lenvima) plus pembrolizumab is a regimen currently under exploration. Moreover, because many patients with HNSCC (up to 30%) exhibit PIK3CA alterations, other research is focused on inhibitors in this space. It also crucial to recognize that not all patients will benefit from IO, she added, and that investigators continue to learn about the molecular biology of the different genomic profiles to provide more options to patients.

She concluded by noting that PD-L1 expression is a key factor in determining a frontline regimen for patients whether its chemotherapy alone, in combination with IO, or IO monotherapy.

“Involving the patient individual factors is important in the initiation of treatment as well as in [making] decisions about whether [a regimen] needs to be added—or reduced [because of] toxicity,” she summarized.


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. 2022;40(21):2321-2332. doi:10.1200/JCO.21.02198

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