Toxicity, Swallow Function, and Quality of life on MC1273, a Phase 2 Study of Dose De-escalation for Adjuvant Chemoradiation in HPV+ Oropharynx Squamous Cell Carcinoma

Adjuvant therapy for oropharynx squamous cell carcinoma (OPSCC) has rates for acute grade ≥3 dysphagia and late grade ≥2 toxicities of 37% and 55% (RTOG 0234). The goal of MC1273 is to determine if dose de-escalation to 30-36 Gy after surgery and neck dissection for patients (pts) with HPV+ OPSCC can maintain rates for disease control (primary endpoint) while reducing short and long-term side effects (secondary endpoints). Eligible pts had p16+ OPSCC, ≤10 pack-year smoking, and R0 resection. Cohort A (≥T3, ≥N2, lymphovascular invasion, or perineural invasion) received 30 Gy in 1.5 Gy BID over 12 days with weekly docetaxel (15 mg/m2). Pts with +ECE (Cohort B) received the same treatment plus a boost to ECE+ nodal levels to 36 Gy in 1.8 Gy BID using a simultaneous integrated boost technique. Pts received a modified barium swallow impairment profile (MBSImP) at baseline (BL), 1 month (mo) post, and 12 mo post-RT. Pts also had patient-reported QOL assessments consisting of the University of Michigan Xerostomia QOL Scale (XeQOLS), Functional Assessment of Cancer Therapy-HN (FACT-HN), European Quality of Life (Eq)-5D, and EORTC-HN assessed at BL and 1, 3, 12, and 24 mo post–radiation therapy (RT). Accrual was 9/2013 – 6/2016 (n= 80, A: 37, B: 43). Median follow-up was 24 mo. No pts have died or been lost to follow-up. Grade 1/2/≥3 toxicity rates at BL (post-op, n=78), 1 mo (n=78), 3 mo (n=78), 12 mo (n=71), and 24 mo (n=29) were 60%/12%/3%, 86%/15%/6%, 82%/17%/3%, 72%/1%/0%, and 59%/10%/0%. All grade ≥3 toxicity occurred by 3 mo and resolved by 6 mo. One pt had a grade 4 infusion reaction to docetaxel that resolved with treatment. Common late grade 2 toxicities were xerostomia and lymphedema (5%), and dysphagia, fatigue, and dysgeusia (3%). No pts required a feeding tube (PEG) due to RT. Oral swallow study scores worsened from BL to 1 mo post RT (n=76; 1.5±1.9 to 2.0±2.2, P=.0476) but recovered at 1 year post RT (n=61; 1.5±1.9 to 1.5±1.8, P=.68). For pharyngeal swallow, scores were stable from BL to 1 mo post RT (n=76; 5.8±3.9 to 5.8±3.7, P=.9176) and significantly improved by 1 year (n=61; 5.8±3.9 to 4.7±3.6, P=.0194). Evaluable pts for QOL endpoints were 78 (BL), 66 (1 mo), 67 (3 mo), 53 (12 mo), and 25 (24 mo). Only the XeQOLs worsened at 1 and 3 mo post-RT (P