Pathologic response and surgical conversion after preoperative docetaxel, cisplatin, and oral 5-FU with or without PD-1 inhibitors in resectable HNSCC: A retrospective cohort study.

Abstract

e18072 Background: Induction chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF) has been widely used in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC), but its clinical utility is often limited by substantial toxicity. A modified regimen consisting of docetaxel, cisplatin, and oral tegafur–uracil (DCU) has been adopted as a more tolerable alternative. Immune checkpoint inhibitors have demonstrated a survival benefit in recurrent or metastatic HNSCC (KEYNOTE-048) and have shown promising efficacy in the perioperative setting (KEYNOTE-689), providing a rationale for exploring adding chemotherapy to perioperative pembrolizumab for resectable HNSCC, based on the KEYNOTE-689 study results. Methods: We conducted a retrospective cohort study of patients resectable HNSCC who received DCU-based induction chemotherapy at Linkou Chang Gung Memorial Hospital between August 2024 and December 2025. A total of 59 patients were included, of whom 37 received DCU alone and 22 received pembrolizumab plus DCU (PDCU). Outcomes included progression-free survival (PFS), overall survival (OS), pathological and clinical responses, conversion to definitive surgery, and treatment-related adverse events (AEs) graded according to CTCAE v5.0. Results: Patients treated with PDCU showed numerically longer PFS and OS compared with those receiving DCU alone; however, no statistically significant differences were observed. Pathologic complete response (pCR) was achieved in 33% in the PDCU group, whereas no pCR was observed in the DCU group. In addition, a higher proportion of patients treated with PDCU underwent definitive surgery compared with those receiving DCU alone (41% vs. 14%), with higher clinical response rates. Treatment-related AEs were generally manageable in both groups, and the addition of pembrolizumab did not result in a marked increase in severe toxicity. Those who did not accept surgery proceeded from concurrent chemoradiotherapy with the following maintenance therapy with pembrolizumab or oral tegafur-uracil for a one-year course (ongoing). Conclusions: In this real-world cohort of patients with resectable HNSCC, induction DCU demonstrated acceptable efficacy and tolerability. The addition of pembrolizumab was feasible and associated with higher pCR rates and increased conversion to surgery. These findings warrant further investigation of pembrolizumab-based induction strategies with longer follow-up and larger prospective studies.