Multicenter phase 2 trial of neoadjuvant triplet chemotherapy to avoid radiotherapy in HPV-associated OPSCC

A multicenter phase 2 trial in Japan assessed a novel de-escalation strategy of neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (NAC-TPF) to avoid postoperative radiotherapy (PORT) and postoperative chemoradiotherapy (POCRT) for resectable HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Treatment started with three cycles of NAC-TPF, followed by surgery. The primary endpoint was centrally reviewed pathological complete response rate (pCR) after NAC-TPF. Of 32 eligible patients, 30 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 quality of life scores recovered to baseline values or improved within 1 year. Twenty-three patients (77%) showed undetectable ctHPV DNA levels after NAC-TPF. The authors conclude that, although the primary endpoint was not met, NAC-TPF in HPV-associated OPSCC achieved clinically meaningful pCR, enabling avoidance of PORT/POCRT in the majority of patients (graphical abstract).