[Nonimmunological systemic therapies in head and neck cancer : Cytotoxic, targeted, EGFR-directed, and supportive approaches at ASCO 2026].

Authors

Markus Blaurock, Philippe Schafhausen, Henrike B Zech

Published in

HNO. Oct 15, 2026. Epub Oct 15, 2026.

Abstract

Systemic treatment of head and neck cancer is dominated by checkpoint inhibitors. Beyond immunotherapy, the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting presented data on chemotherapy, epidermal growth factor receptor (EGFR)-directed agents, novel routes of administration, and supportive care.
The aim was to appraise the studies on nonimmunological systemic therapy presented at ASCO 2026 and to derive recommendations for practice.
A structured review of all 329 head and neck-related abstracts presented at the 2026 ASCO Annual Meeting was created. Non-checkpoint-inhibitor-dominant approaches were included, with justified exceptions for combination regimens; of 72 studies, 67 reported results and 58 contained interpretable signals. Salivary gland, thyroid, and sinonasal cancers are covered elsewhere.
Three phase III trials met their prespecified noninferiority criteria for de-escalated or toxicity-reduced regimens in nasopharyngeal cancer, albeit within wide margins (8%-10%). The metronomic adjuvant chemotherapy study (MACE postop) missed its primary overall survival (OS) endpoint (79.2% vs. 70.2%; hazard ratio, HR, 0.76) with a borderline positive progression-free survival (PFS) signal. In first-line palliative treatment, oral metronomic chemotherapy plus ultra-low-dose nivolumab prolonged survival versus paclitaxel/carboplatin (10.3 vs. 6.2 months; HR 0.565). Amivantamab achieved a 47% response rate after platinum and PD-(L)1 failure; photoimmunotherapy missed both co-primary endpoints. Positive nimotuzumab signals derived from an abstract-only publication.
The nasopharyngeal trials are methodologically the strongest, but noninferiority is not equivalence, and transferability to other head and neck cancers is not established. No purely cytotoxic or targeted therapy has established a new standard in head and neck squamous cell carcinoma (HNSCC); low-cost metronomic regimens and EGFR-directed combinations are promising, supportive approaches remain exploratory.

PMID:
42878801
Bibliographic data and abstract were imported from PubMed on 16 Oct 2026.

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