TOPLINE

In a phase 2 trial of patients with locally advanced head and neck squamous cell carcinoma (HNSCC), neoadjuvant immunochemotherapy (ICT) followed by response-adapted surgery showed promise: Patients who responded to ICT and underwent reduced-volume surgery had a 2-year disease-free survival of 90% and universal laryngeal preservation.

METHODOLOGY

• Standard treatment for locally advanced HNSCC, including radical surgery followed by radiation with or without chemotherapy, comes with a high recurrence rate and considerable long-term toxicity. Recent evidence shows that neoadjuvant ICT can achieve significant tumor regression, creating a potential window for surgery de-escalation.
• To further investigate, researchers conducted the single-arm phase 2 REMATCH trial, enrolling 52 patients with resectable, HPV-negative locally advanced HNSCC from health systems in Wuhan, China. 
• All patients received three cycles of neoadjuvant ICT (penpulimab 200 mg, albumin-bound paclitaxel 230 mg/m², and cisplatin 75 mg/m²) on day 1 of each 21-day cycle. Tumor response was evaluated before the third cycle; patients with more than 50% primary tumor regression underwent reduced-volume surgery, and those with less than 50% regression underwent standard surgery. All received adjuvant radiotherapy followed by nine cycles of maintenance immunotherapy. 
• The primary endpoint was 2-year disease-free survival, with secondary endpoints including objective response rate, pathologic complete response rate, R0 resection rate, organ preservation, and 2-year overall survival. 

TAKEAWAY

• Among 50 patients evaluated before the third ICT cycle, the objective response rate was 94%, with 90% achieving more than 50% primary tumor regression. 
• Among 47 patients undergoing resection, the R0 resection rate was 89%, with pathologic complete response and major pathologic response rates of 40% and 70%, respectively. Patients who underwent reduced-volume surgery showed superior surgical outcomes, with R0 in 93%, pathologic complete response in 45%, and major pathologic response in 79%. 
• At a median follow-up of 34 months, 2-year disease-free survival was 90% among patients who received reduced-volume surgery compared with 20% among those who received standard surgery. Two-year overall survival rates were 93% and 50%, respectively. 
• Among 39 patients undergoing reduced-volume surgery for laryngeal or hypopharyngeal tumors, laryngeal preservation was 100%. In contrast, 1 of 3 such patients undergoing standard surgery had complete loss of laryngeal function. 

IN PRACTICE

“The REMATCH trial provides the first prospective evidence that a response-adapted surgical strategy after [neoadjuvant] ICT is feasible,” the study authors wrote. “Patients achieving >50% primary tumor regression derived promising survival and universal laryngeal preservation. These findings support the initiation of phase III randomized trials to validate this de-escalation strategy.”

SOURCE

The study, led by Xiaomeng Zhang, of Tongji Medical College, Huazhong University of Science and Technology in Wuhan, was published online in Clinical Cancer Research.

LIMITATIONS

The study lacked a randomized control group to directly compare reduced-volume and standard surgery. The cohort predominantly comprised laryngeal and hypopharyngeal cancers (90%), which may limit generalizability to other head and neck cancer subsites. The relatively short follow-up may not capture late recurrences, and the small sample size limits the ability to draw definitive conclusions about outcomes, particularly in patients with poor response to ICT.

DISCLOSURES

The trial was supported by the National Natural Science Foundation of China and the Key Research and Development Program of Hubei Province. The authors reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.