What is the role of immunotherapy in the treatment of head and neck cancers?

From the Guidelines

Immunotherapy plays a crucial role in the treatment of head and neck cancers, particularly for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), with immune checkpoint inhibitors like pembrolizumab and nivolumab being the primary agents used. The use of immunotherapy in head and neck cancers has been supported by recent guidelines, including the ASCO guideline on immunotherapy and biomarker testing in recurrent and metastatic head and neck cancers 1.

Key Points

• Immunotherapy is effective for patients with platinum-refractory recurrent or metastatic HNSCC, with response rates varying between 15-20% as monotherapy 1.
• Pembrolizumab may be used as first-line treatment in combination with chemotherapy for metastatic disease, and is also approved for the treatment of TMB-high advanced rare head and neck cancers 1.
• Biomarkers like high PD-L1 expression or high tumor mutational burden may predict better outcomes with immunotherapy 1.
• The addition of immunotherapy to first-line treatment with cisplatin and gemcitabine has shown an increase in progression-free survival (PFS) for recurrent and/or metastatic nasopharyngeal carcinoma (NPC) 1.

Treatment Considerations

• Treatment duration typically continues until disease progression or unacceptable toxicity, with some patients receiving therapy for up to two years.
• Common side effects of immunotherapy include fatigue, rash, and immune-related adverse events affecting organs like the thyroid, lungs, or liver, requiring regular monitoring.
• The role of immunotherapy in rare head and neck cancers, such as salivary gland carcinomas, is also being explored, with pembrolizumab being approved for the treatment of TMB-high advanced rare head and neck cancers 1.

Recent Guidelines

• The ASCO guideline on immunotherapy and biomarker testing in recurrent and metastatic head and neck cancers provides recommendations for the use of immunotherapy in this setting 1.
• The ESMO-EURACAN clinical practice guideline update for nasopharyngeal carcinoma also provides recommendations for the use of immunotherapy in the treatment of NPC 1.

From the FDA Drug Label

The efficacy of KEYTRUDA was investigated in KEYNOTE-048 (NCT02358031), a randomized, multicenter, open-label, active-controlled trial conducted in 882 patients with metastatic HNSCC who had not previously received systemic therapy for metastatic disease or with recurrent disease who were considered incurable by local therapies.

Table 70: Efficacy Results* for KEYTRUDA plus Platinum/Fluorouracil in KEYNOTE-048

Endpoint	KEYTRUDA 200 mg every 3 weeks Platinum FU	Cetuximab Platinum FU
OS
Number (%) of patients with event	197 (70%)	223 (80%)
Median in months (95% CI)	13.0 (10.9,14.7)	10.7 (9.3,11.7)
Hazard ratio* (95% CI)	0.77 (0.63,0.93)
p-Value*	0.0067

The role of immunotherapy in the treatment of head and neck cancers is established as a viable option, with KEYTRUDA (pembrolizumab) demonstrating a statistically significant improvement in Overall Survival (OS) compared to chemotherapy alone in patients with metastatic or unresectable, recurrent head and neck squamous cell cancer (HNSCC).

• KEYTRUDA in combination with chemotherapy showed a hazard ratio of 0.77 for OS, indicating a reduced risk of death compared to cetuximab in combination with chemotherapy.
• The median OS was 13.0 months for the KEYTRUDA combination arm, compared to 10.7 months for the cetuximab combination arm.
• Additionally, nivolumab (OPDIVO) has shown statistically significant improvement in OS for patients with recurrent or metastatic squamous cell carcinoma of the head and neck, with a hazard ratio of 0.70 compared to investigator’s choice of therapy 2 3.

From the Research

Overview of Immunotherapy in Head and Neck Cancers

• Immunotherapy has significantly improved the outcome of recurrent metastatic squamous cell carcinoma of the head and neck (SCCHN) 4.
• The anti-PD-1 antibody drugs nivolumab and pembrolizumab are the only immunotherapies with proven efficacy in head and neck cancer 4.
• Combinations of immunotherapy with cancer drugs and treatment modalities, such as radiation therapy and surgery, are being investigated to improve efficacy and safety 4, 5.

Current Status of Immunotherapy in Head and Neck Cancers

• Immunotherapy, especially immune checkpoint inhibitors (ICIs) like pembrolizumab and nivolumab, has contributed to significant improvements in treatment outcomes and survival of head and neck cancer patients 5.
• However, only a subset of patients benefits from ICIs, and identifying combination therapies to improve response rates is an active area of research 5.
• Ongoing clinical trials are investigating the combination of targeted therapy with immunotherapy, including the use of novel immunotherapeutic agents like durvalumab, atezolizumab, and avelumab 6.

Challenges and Future Directions

• The selection criteria for immune checkpoint inhibitors and the optimization of combination regimens are challenges that need to be addressed to maximize the benefits of immunotherapy in head and neck cancers 7.
• There is a lack of knowledge on how to incorporate molecular biomarkers as predictors of response to head and neck cancer immunotherapy 7.
• A more personalized approach to metastatic or recurrent head and neck cancer therapy should be followed, considering the role of the microbiome in immunotherapy and the limitations of immunotherapy 6.

Consensus Guidelines and Recommendations

• The Society for Immunotherapy of Cancer (SITC) has generated consensus recommendations for emerging immunotherapies, including patient selection, therapy sequence, response monitoring, adverse event management, and biomarker testing 8.
• These guidelines serve as a foundation to assist clinicians' understanding of the role of immunotherapies in head and neck cancer and to standardize utilization across the field for patient benefit 8.