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

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). 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. 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. 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.