Selective Treatment Deintensification by Reducing Radiation Dose and Omitting Concurrent Chemotherapy Based on Response to Induction Chemotherapy in Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma: A Single-Arm, Phase 2 Trial (IChoice-01)

Abstract

Purpose: To demonstrate the feasibility of deintensification regimen in the light of the response to induction chemotherapy (IC) in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC).

Methods and materials: Patients with p16+ OPSCC, T1-2/N1-3M0 (excluding T1N1M0 with single and ≤3 cm lymph node) or T3-4N0-3M0 were enrolled between January 2019 and July 2021. All patients received 2 cycles of IC with docetaxel 75 mg/m² dL and cisplatin 75 mg/m² dL every 3 weeks. Those with major responses (≥50% decrease in both primary and lymph nodes) to IC entered the deintensification cohort (cohort D), in which intensity modulated radiation therapy alone was given to a reduced dose of 60 Gy/30 fractions. Those who failed to meet major responsesentered the concurrent chemoradiotherapy cohort (cohort C), where the dose was simultaneously integrated boosted to a standard 70 Gy/35 fractions to nonmajor response sites, concurrently with cisplatin 80 mg/m² dL,22. Patient-reported swallow function was documented using the MD Anderson Dysphagia Inventory. The primary endpoint was 2-year progression-free survival (PFS) using Simon's 2 stage design.

Results: A total of 26 of 48 (54.2%) participants met the criteria to enter cohort D and 22 of 48 (45.8%) patients entered cohort C. With a median follow-up time of 29.7 months (6.9-48.0 months), 2-year PFS and OS rates were 85.4% and 93.6%, respectively for all enrolled patients. In cohort D, 2-year PFS and OS rates were both 100%. Grade 3 and 4 IC-related toxicities included leukopenia/neutropenia occurring in 41.7% and hyponatremia in 4.2% of patients. A higher incidence of grade 3 and 4 mucositis (61.9% vs 23.1% P = .022) was observed in cohort C. Consistent decline in longitudinal MD Anderson Dysphagia Inventory scores were observed at month 3 after radiation therapy between cohorts and both were found to recover to baseline at month 12.

Conclusions: Selective radiation therapy dose reduction and concurrent chemotherapy removal based on IC response in HPV + OPSCC was feasible and promising. Further study of this strategy to balance efficacy and toxicity is warranted in a prospective controlled trial.