E1308: Reduced-dose IMRT in human papilloma virus (HPV)-associated resectable oropharyngeal squamous carcinomas (OPSCC) after clinical complete response (cCR) to induction chemotherapy (IC).

Head and Neck Cancer
Session Type and Session Title: 
Oral Abstract Session, Head and Neck Cancer
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr LBA6006)
Anthony Cmelak, Shuli Li, Shanthi Marur, Weiqiang Zhao, William H. Westra, Christine H. Chung, Maura L. Gillison, Jill Gilbert, Julie E. Bauman, Lynne I. Wagner, Robert L. Ferris, David R. Trevarthen, A. Dimitrios Colevas, Balkrishna N. Jahagirdar, Barbara Burtness; Vanderbilt-Ingram Cancer Center, Nashville, TN; Dana-Farber Cancer Institute, Boston, MA; The Johns Hopkins University School of Medicine, Baltimore, MD; The Ohio State University, Columbus, OH; The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH; Vanderbilt University, Nashville, TN; University of Pittsburgh Cancer Institute, Pittsburgh, PA; Feinberg School of Medicine, Northwestern University, Chicago, IL; University of Pittsburgh School of Medicine, Pittsburgh, PA; Colorado Cancer Research Program, Denver, CO; Stanford University, Stanford, CA; HealthPartners and Regions Cancer Care Center, St. Paul, MN; Fox Chase Cancer Center, Philadelphia, PA

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Abstract Disclosures


Background: HPV+ patients (pts) in E2399 obtained a 2-yr 95% survival and 86% PFS after IC and 70Gy chemoradiation. We hypothesized reduced-dose IMRT (54Gy, 23% reduction) in HPV+ OPSCC pts could maintain high LR control and 85% 2-yr PFS in pts with cCR to IC. Methods: Pts with resectable stage III/IVa,b HPV+ OPSCC received IC q3 weeks x 3 with paclitaxel 90mg/m2 days (D) 1,8,15, cisplatin 75mg/m2 D1, and standard cetuximab (Cetux) weekly schedule. IC response determined IMRT dose independently at primary and involved nodes: IMRT 54Gy/27 if cCR vs. 69.3Gy/33 if <cCR. Cetux was continued during IMRT. Primary endpoint was 2-yr PFS. Results: 90 pts were enrolled (80 analyzable). Med FU is 23.3 months (mo). Tumor and Nodal stage: T4-10%, T3-17%, T2-50%, and T1-23%; N0,1-16%, N2a,b-54%, N2c-31%. Med age 57yrs. 46% never smoked and 84% not current smokers. IC and C-IMRT was well tolerated: 96% received all 3-cycles of IC. 71% had cCR. 62 pts (78%) received reduced-dose Cetux-IMRT. For all reduced IMRT pts, 23mo PFS is 84%, primary site LC 94%, nodal control 95%, and distant 92%. Post-treatment neck dissection was positive for tumor in 4/8 reduced dose IMRT pts compared to 1/3 pts treated with std dose. One late grade 3 toxicity occurred in 1 reduced-dose pt: hypomagnesemia at 30mo. Conclusions: IC + reduced-dose Cetux-IMRT produced high tumor control rates. Late toxicities were minimal. Low dose pts achieved 84% PFS at 23mo and 95% 2-yr survival. Pts with <10yrs smoking, T1-3 and N0-2b disease achieved 96% PFS. Further studies of reduced-dose IMRT in chemoresponsive HPV+ pts are warranted. Clinical trial information: NCT01084083.

Variable (n) 23mo PFS (90% CI) 24mo OS (90% CI)
All reduced-dose pts ( 62) 0.84 (0.74, 0.90) 0.95 (0.87, 0.98)
T4A (7) 0.69 (0.29,0.89) 0.86 (0.45, 0.97)
T1-T3(55) 0.86 (0.75, 0.92) 0.96 (0.88, 0.99)
N2C (19) 0.77 (0.56, 0.89) 0.95 (0.76, 0.99)
N0-N2b(43) 0.87 (0.75, 0.94) 0.95 (0.85, 0.98)
Smoker > 10 pkyr (21) 0.71 (0.48, 0.85) 0.90 (0.71, 0.97)
Smoker <= 10 pkyr (40) 0.92 (0.81, 0.97) 0.97 (0.87, 0.995)
Smoker<=10 pkyr,
<T4, <N2c (n=27)
0.96 (0.82, 0.99) 0.96 (0.82, 0.99)
All standard-dose pts (15) 0.64 (0.39, 0.81) 0.87 (0.63, 0.96)