Retrospective cohort study of pathologic response after neoadjuvant chemoimmunotherapy versus immunotherapy in HNSCC

Treatment outcomes for locally advanced head and neck squamous cell carcinoma (HNSCC) are suboptimal. Neoadjuvant immunotherapy (NAI) has shown promise, but pathologic response rates remain modest with single-agent regimens. A retrospective cohort study at Icahn School of Medicine at Mount Sinai (New York, NY) compared rates of pathologic response between NAI and neoadjuvant chemoimmunotherapy (NACI) for adult patients with resectable HNSCC of the aerodigestive tract. The study included 86 participants who received at least one cycle of NAI (n=28) or NACI (n=58) followed by definitive surgery from July 2024 to March 2026. Primary outcome was pathologic response in the surgical specimen, categorized as pathologic complete response (pCR), major pathologic response (MPR; ≤10% viable tumor), or partial response. Among 86 participants, 29% achieved pCR and 17% achieved MPR. pCR or MPR occurred in 67% (95% CI 54-78) of NACI recipients compared with one (3.6%) of the NAI recipients. In propensity score-adjusted analysis, NACI was associated with higher odds of pCR or MPR (odds ratio 29.1; 95% CI 6.7-274.7) compared with NAI. Treatment was generally well tolerated, with few adverse event-related delays to surgery. The authors conclude that these findings support the potential role of neoadjuvant combination regimens in resectable HNSCC, although prospective trials are needed to determine effects on survival.