Neoadjuvant triplet chemotherapy enables radiotherapy avoidance in human papillomavirus-associated oropharyngeal cancer: a multicentre Phase II trial.

BACKGROUND: This prospective Phase 2 trial assessed a novel de-escalation strategy for upfront neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (NAC-TPF) to avoid postoperative radiotherapy (PORT) and chemoradiotherapy (POCRT) for human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). METHODS: Patients with HPV-associated resectable OPSCC were enrolled. Invasive surgery or PORT/POCRT was an inclusion criterion if upfront surgery was performed. Treatment started with three cycles of NAC-TPF, followed by surgery. The primary endpoint was the centrally reviewed pathological complete response (pCR) rate after NAC-TPF. Levels of high-risk HPV RNA in tumor specimens and plasma circulating tumor (ct) HPV DNA, and quality of life (QOL) scores were assessed. RESULTS: Of 32 eligible patients, 30 patients underwent transoral surgery after NAC-TPF. R0 resection was confirmed in 31 patients. pCR and virological complete response rate at both the primary site and lymph nodes were 65.6% and 64.5%, respectively. No PORT/POCRT was performed in 91%. All QOL scores recovered to baseline values or improved within 1 year. Twenty-three patients showed undetectable ctHPV DNA levels after NAC-TPF. CONCLUSION: Although the primary endpoint was not met, NAC-TPF in HPV-associated resectable OPSCC achieved clinically meaningful pCR, enabling avoidance of PORT/POCRT in the majority of patients. (Clinical trial registration numbers: jRCT1041220029).