MC1675, a Phase III Evaluation of De-Escalated Adjuvant Radiation Therapy (DART) vs. Standard Adjuvant Treatment for Human Papillomavirus Associated Oropharyngeal Squamous Cell Carcinoma

Abstract

<h3>Purpose/Objective(s)</h3> We previously reported the results of a phase II clinical trial evaluating 30-36 Gy of adjuvant radiation therapy (RT) for selected patients with HPV+ OPSCC. Herein we report the two-year results of a phase III trial comparing this 30-36 Gy regimen with standard of care (SOC) adjuvant RT. <h3>Materials/Methods</h3> All patients (pts) received transoral robotic surgery (TORS) and neck dissection for a margin negative resection. Pts with pT4 disease or who required >2 attempts to clear margins were excluded. Pts with intermediate risk factors received 30 Gy/1.5 Gy b.i.d. + docetaxel 15 mg/m² days 1 and 8, while pts with extranodal extension (ENE) simultaneously received 36 Gy/1.8 Gy b.i.d. to ENE+ nodal levels. Pts were randomized (2:1) to DART or SOC (60 Gy ± weekly cisplatin 40 mg/m²). Stratification was by risk group (intermediate risk vs ENE+) and smoking status (< vs ≥10 pack-yr). The primary endpoint was grade ≥3 AE rate ≥3 mos after RT with the study powered to have 90% power to detect a grade ≥3 AE rate reduction from 25% to 7%. Secondary endpoints were OS, LRC, PFS, and QOL. Pts received a swallow evaluation (MBSImP) before, 1 mo, and 1 yr post-RT. Pts also had QOL assessed with the FACT-HN, EORTC-HN35, and University of Michigan Xerostomia QOL Scale (XeQOLS) pre-RT and 1, 3, 12, and 24 mos post-RT. <h3>Results</h3> Accrual was from 10/16 – 8/20 (n = 194, DART: 130, SOC: 64, ENE+: 115 (59%), Non-smokers: 139 (72%), median age 59.4 yrs (37.9-81.6), male 89%. Median follow-up as of 7/21 was 25.3 mo. 1.6% DART and 27.4% SOC pts (p<0.0001) required a feeding tube. Grade ≥3 AEs at 3 months were 1.6% DART vs 7.1% SOC (p = 0.058). Swallowing function change from baseline to 1 month was superior in the DART arm (DART vs SOC, median) MBSImP: -0.3 vs -2.6 (p = 0.0155) as was baseline to 3 month QOL FACT-HN: 5.1 vs -3.2 (p = 0.0007); EORTC-HN Pain: -8.6 vs 2.5 (p = 0.0009); XeQOLS: 2.9 vs 11.7 (p = 0.0001). 2 yr statistics between DART and SOC arms were similar except for PFS on the DART/ENE+ arm (Table). PFS on the DART/ENE+ arm was driven by the pN2 cohort (AJCC 8, >4 LN). For ENE+/pN0-1 pts, (DART vs SOC) 2 yr PFS was 89.6% vs 95.8%; LRC 95.8% vs 100.0%; DMFS 96.4% vs 95.8%. For ENE+/pN2 (DART vs SOC) PFS was 42.9% vs 100%; LRC 77.0% vs 100%; DMFS 59.4% vs 100%. <h3>Conclusion</h3> DART demonstrated less toxicity, improved swallowing function and QOL when compared to SOC. DART also had excellent LRC, PFS, and OS rates, particularly in the ENE negative cohort. Caution is advised for de-escalating ENE+ pts with pN2 disease.