Author: Mark L. Fuerst , Contributing Writer, MedPage Today
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Immunotherapy with anti–programmed cell death protein 1 (PD-1) immune checkpoint inhibitors (ICIs) is now an essential treatment for patients with recurrent and metastatic head and neck squamous cell carcinoma (HNSCC), and ICIs also show promise for patients with nasopharyngeal carcinoma and other rare head and neck cancer types.
A recently released ASCO Guideline on immunotherapy and biomarker testing in recurrent and metastatic HNSCCs provided evidence-based recommendations. A new related document by expert panel co-chairs Emrullah Yilmaz, MD, PhD, of the Cleveland Clinic, and Loren K. Mell, MD, of the University of San Diego, and colleagues poses questions and answers about the guideline. The following is a summary:
For patients with recurrent and metastatic head and neck cancer, which biomarkers should be used in the selection of anti–PD-1 immune checkpoint inhibitor therapy?
We recommend programmed death ligand 1 (PD-L1) combined positive score (CPS) testing for recurrent and metastatic HNSCC. PD-L1 reports come via immunohistochemistry using CPS or tumor proportion score. CPS has emerged as a preferred biomarker in HNSCC and has been used in landmark head and neck clinical trials such as KEYNOTE-048.
Tumor mutational burden (TMB), another emerging biomarker for predicting response to anti–PD-1 ICIs, was studied in KEYNOTE-158. TMB is not used routinely in HNSCC, but may help in cases where PD-L1 CPS is unavailable or for rare head and neck cancers.
In first-line treatment of patients with PD-L1 CPS ≥ 1 recurrent and metastatic HNSCC, can pembrolizumab be used alone or with chemotherapy?
Pembrolizumab alone can be considered for patients with CPS ≥ 1; however, for patients with high disease burden where an early response is required, pembrolizumab and chemotherapy can be considered regardless of the PD-L1 expression.
The KEYNOTE-048 trial evaluated the role of pembrolizumab as a single agent or in combination with chemotherapy versus chemotherapy and cetuximab in first-line treatment of patients with recurrent or metastatic HNSCC. Patients with CPS ≥ 1 had improved overall survival (OS) with pembrolizumab monotherapy compared with cetuximab and chemotherapy.
Patients with CPS ≥ 20 had the greatest benefit from pembrolizumab monotherapy. OS benefit was observed in the overall population with pembrolizumab and chemotherapy, making this another option for patients with PD-L1 positive HNSCC.
In first-line treatment of patients with PD-L1 CPS < 1 recurrent and metastatic HNSCC, can pembrolizumab be used alone or in combination with chemotherapy?
Pembrolizumab and chemotherapy remain an option for patients with CPS < 1, but cetuximab and chemotherapy could also be considered for these patients.
Subgroup analysis of KEYNOTE-048 for patients with CPS < 1 did not show a statistically significant difference in OS with pembrolizumab and chemotherapy compared with cetuximab and chemotherapy groups. However, there were a small number of patients in this subgroup, and the study was not powered to evaluate efficacy for CPS < 1.
Which immunotherapy should be used in patients with platinum-refractory recurrent and metastatic HNSCC?
Either nivolumab or pembrolizumab are appropriate systemic options regardless of PD-L1 status in patients with platinum-refractory HNSCC.
Two large, randomized phase III studies have confirmed the efficacy of anti–PD-1 ICIs in platinum-refractory HNSCC. CheckMate 141 compared nivolumab, and KEYNOTE-040 compared pembrolizumab with standard-of-care chemotherapy for platinum-refractory HNSCC.
Both nivolumab and pembrolizumab prolonged OS in these two studies, and response to immunotherapy was independent of PD-L1 expression.
Should immunotherapy be used in patients with recurrent and metastatic nasopharyngeal carcinoma?
Pembrolizumab or nivolumab may be offered in combination with gemcitabine and cisplatin for first-line treatment of recurrent or metastatic nasopharyngeal carcinoma.
The combination of anti-PD-1 ICIs with gemcitabine and cisplatin was shown to be effective in recurrent or metastatic nasopharyngeal carcinoma in several phase III studies from Asia. JUPITER-02, CAPTAIN-1, and RATIONALE-309 studies used toripalimab, camrelizumab, and tislelizumab, respectively, in combination with gemcitabine and cisplatin — all showing progression-free survival benefit in recurrent or metastatic nasopharyngeal carcinoma.
The role of the anti–PD-1 inhibitors in platinum-refractory nasopharyngeal carcinoma without prior ICI use is not well established. However, responses to anti–PD-1 ICIs are comparable with chemotherapy with a better safety profile, so they may be considered in the platinum-refractory setting as single-agent therapy.
Can radiation therapy be given in combination with immunotherapy for the treatment of recurrent or oligometastatic HNSCC?
Radiation therapy is safe to give to patients with recurrent and metastatic HNSCC in combination with immunotherapy, and should be considered for palliation or local control.
Anti–PD-1 inhibitors and stereotactic body radiation therapy combinations have not been shown to increase efficacy for abscopal effect for the treatment of oligometastatic disease in HNSCC. However, there are several ongoing studies to evaluate the efficacy of stereotactic body radiation therapy with immunotherapy for locoregional disease.
Can immunotherapy be used for patients with rare head and neck cancers?
Pembrolizumab may be considered for patients with advanced rare head and neck cancers with limited treatment options, if high tissue TMB is identified.
KEYNOTE-158 has shown the effectiveness of pembrolizumab in patients with advanced cancer with high tissue TMB defined as ≥ 10 mutations per megabase.
Pembrolizumab has also shown activity in patients with salivary gland cancers expressing ≥ 1% PD-L1 and may therefore be considered in such patients with advanced recurrent or metastatic salivary gland cancers with ≥ 1% PD-L1.
Read the guideline summary here.
JCO Oncology Practice
Source Reference: Yilmaz E, et al “Immunotherapy and biomarker testing in recurrent and metastatic head and neck cancers: ASCO Guideline Q and A” JCO Oncol Pract 2023; 19: 194-196.