The Current Treatment Pathways for Head and Neck Cancers
Key Points
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Surgery in resectable patients and definitive radiation or chemoradiation in unresectable patients are the primary treatment modalities for early-stage head and neck squamous cell carcinoma.
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Human papillomavirus (HPV) status has a large impact on prognosis and treatment pathways in head and neck cancer.
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Immunotherapy is gaining ground in head and neck cancer treatment, with perioperative pembrolizumab approved for resectable disease based on KEYNOTE-689.
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Multidisciplinary collaboration is key for these disease sites, given the potential impact on speech and nutrition.
Head and Neck Carcinoma Treatment Options
Fangdi Sun, MD, of Stanford University, joined the Oncology Brothers podcast cohosts, Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, to discuss the treatment algorithm for patients with head and neck cancers. The doctors covered the primary treatments for mucosal head and neck squamous cell carcinoma populations, the relevance of HPV status, and the distinct treatment pathway for nasopharyngeal carcinomas.
Initial Workup for Primary Tumors
The discussion first covered the standard workup for head and neck cancers. First, oncologists visualize the tumor. For oral cavity cancers, this can be assessed directly on physical examination; however, other disease sites require fiber-optic endoscopy. Further imaging includes anatomic scanning of the primary site and neck, typically with MRI or CT, as well as PET/CT or systemic CT imaging.
There are only a few relevant biomarkers in head and neck cancers. Immunohistochemistry (IHC) for PD-L1 status should be performed across early and advanced disease settings. For oropharynx tumors specifically, IHC for p16 protein to indicate HPV status and risk is necessary, as HPV–positive and HPV–negative cancers have different risk factors, prognosis, and treatment pathways. Next-generation sequencing has a limited role in initial workup, as most head and neck cancers are squamous cell cancers and lack actionable targets, said Dr. Sun.
Treating Mucosal Head and Neck Squamous Cell Cancer
Surgery is the primary treatment for resectable, early, or limited-stage mucosal head and neck squamous cell carcinoma. Patients with high-risk disease features also receive adjuvant radiation, chemotherapy, or both. For unresectable early-stage disease, the primary treatment strategy is definitive chemoradiation plus systemic therapy. Cisplatin is the preferred systemic agent pairing, and many oncologists use a lower-dose weekly administration instead of standard cisplatin dosing in this setting, said Dr. Sun.
The latest treatment approval for earlier stages is perioperative pembrolizumab for patients with PD-L1–positive stage III/IVA resectable mucosal head and neck squamous cell carcinomas, based on the KEYNOTE-689 trial. This regimen is appropriate for PD-L1–positive, HPV–negative patients. However, there is some concern that tumor progression during neoadjuvant therapy could cause previously resectable patients to become unresectable, said Dr. Sun.
For advanced or metastatic mucosal head and neck squamous cell carcinoma, the standard first-line therapy is pembrolizumab or pembrolizumab plus chemotherapy based on the KEYNOTE-048 study. The trial showed that pembrolizumab monotherapy improved overall survival (OS) for patients with a PD-L1 combined positive score of 1 or greater, and pembrolizumab plus chemotherapy improved OS for all patients.
In clinical practice, pembrolizumab plus chemotherapy may still be appropriate for PD-L1–positive patients if tumor progression is a concern. For PD-L1–negative patients, platinum-based chemotherapy with pembrolizumab or cetuximab is the current standard treatment, though this population is poorly represented in recent trials, said Dr. Sun.
Compared to HPV–negative head and neck cancers, HPV–positive oropharynx cancer is particularly sensitive to radiation and chemotherapy. In HPV–positive disease, definitive radiation or chemoradiation, again with additional adjuvant therapy for high-risk disease, is preferred over resection to avoid surgical morbidities. Dr. Sun emphasized this is a vaccine-preventable disease. Regardless of disease stage and treatment choice, a multidisciplinary approach to preserve nutrition and speech is crucial for head and neck cancers, the doctors agreed.
Distinct Treatment Algorithm for Nasopharyngeal Carcinoma
The primary treatments for T1N0 patients and T2N0 or stage IB patients are definitive radiation therapy with or without chemotherapy and concurrent chemoradiation, respectively. For stage II/III patients, the standard treatment is induction chemotherapy (usually gemcitabine plus cisplatin), followed by chemoradiation.
Some trial and real-world data support the addition of adjuvant capecitabine in this setting, and Dr. Sun said she routinely recommends it in her practice. Ongoing trials are also evaluating immunotherapy, although none have led to an approval. In advanced or metastatic nasopharyngeal carcinoma, the primary treatment strategy is gemcitabine and cisplatin plus one of two approved PD-L1 inhibitors, toripalimab and penpulimab.
In closing the discussion, Dr. Sun emphasized the importance of multidisciplinary collaboration, as many treatment decisions, particularly in the definitive setting, are “patient and disease specific in a way that isn’t captured by staging systems or risk models.” Even judgment of resectable disease is very patient-specific based on disease characteristics and organ preservation, she added.