E 1308: A phase II trial of induction chemotherapy (IC) followed by cetuximab with low dose versus standard dose IMRT in patients with human papilloma virus (HPV)-associated resectable squamous cell carcinoma of the oropharynx (OPSCC).

Abstract

6005 Background: HPV is associated with 60-80% of OPSCC. E2399 results showed IC followed by (f/b) paclitaxel (P)/3D RT (70Gy) improved 2-yr progression-free (PFS) for HPV+ compared to HPV- OPSCC. We studied a regimen with 20% radiation dose reduction to 54Gy in HPV + OPSCC patients (pts) with a clinical complete response (CCR) to IC. Methods: Stage III/IVA,B resectable HPV+ OPSCC were included. Eligible pts received IC q3 week x 3 with P 90mg/m2 days (D) 1,8, 15, cisplatin (CDDP) 75mg/m2 D1, and cetuximab (C) 400 mg/m2 D1, cycle 1 f/b C 250 mg/m2 weekly. Primary tumor and involved nodal response to IC were determined independently. Pts recieved IMRT 54Gy/27 fxs with weekly C for CCR vs. 69.3Gy/33 fxs with weekly C if <CCR. Primary endpoint was 2-year PFS; secondary endpoints were toxicity, OS, response rate, QOL and correlative biomarkers. Results: From March 2010 to Oct 2011, 90 pts were enrolled (80 analyzable). Median age was 57 years, 95% men, 93% Caucasian, 91% PS 0, 46% never smokers, 84% not current smokers. Nodal stage: 39%-N2B, 29%-N2C, T stage: 23%-T1, 50%-T2, 16%-T3, 10%-T4. 96% received all 3 cycles of IC. Grade 3/4 toxicities included: rash (25%), neutropenia (11%). During CRT: oral mucositis (31%), dysphagia (17%), radiation dermatitis (8%). Response: Biopsy at primary site post- baseline measurements rendered 7/80 pts unevaluable (UE), 6/7 had investigator-reported CCR to IC. The centrally reviewed and investigator reported primary site CCR rate to IC was 63.8% ( 95% CI: 52.2%, 74.2%) and 71.3% (95% CI: 60.0%, 80.8%), respectively. Radiation: 73.8% (59/80 pts) received low dose IMRT/C to primary [54Gy (56), 52Gy (1), 40Gy (2)]. Best overall clinical response was 86% (CR +PR+SD) with 14% UE. Rate of post-treatment neck dissection in low dose vs other RT gp is 13.4% vs 22.2% ( p value of 0.46), respectively. Median follow up is 11.8 months. Conclusions: Overall, IC with P, CDDP and C f/b low dose RT with C was well tolerated, with all pts responding and very low grade 3/4 toxicities. Data on PFS are premature. A 2 year PFS of 85% or better will be considered worthy of further study. Clinical trial information: NCT01084083.