O-0005 - RTOG 0436: a phase III trial of cisplatin, paclitaxel and radiation with or without cetuximab in the nonoperative treatment of esophageal cancer

Date 26 June 2014
Event World GI 2014
Session Esophageal cancer
Topics Anti-Cancer Agents & Biologic Therapy
Oesophageal Cancer
Surgery and/or Radiotherapy of Cancer
Presenter David H. Ilson
Citation Annals of Oncology (2014) 25 (suppl_2): ii105-ii117. 10.1093/annonc/mdu193
Authors D.H. Ilson1, A. Konski2, A. Chakravarthy3, C. Anker4, H. Thakrar5, N. Horiba6, V. Kavadi7, J. Giguere8, M. Deutsch9, A. Raben10, K. Roof11, G. Videtic12, J. Pollock13, K. Winter14, H. Safran15, M. Suntharalingham6, C. Crane16, A. Dicker17, L. Kachnic18
  • 1Memorial Sloan-Kettering Cancer Center, New York/US
  • 2Wayne State University, Detroit/US
  • 3Vanderbilt University, Nashville/US
  • 4University of Utah, Salt Lake City/US
  • 5Hospital of Cook County, Chicago/US
  • 6University of Maryland, Baltimore/US
  • 7Texas Oncology, Sugar Land/US
  • 8Greenville CCOP, Greenville/US
  • 9University of Pittsburgh, Pittsburgh/US
  • 10Christiana Care Health Care, Newark/US
  • 11Southeast Cancer Control Consortium, Winston Salem/US
  • 12Cleveland Clinic, Cleveland/US
  • 13Wheeling Hospital, Wheeling/US
  • 14The Radiation Therapy Oncology Group, Philadelphia/US
  • 15The Brown University Oncology Research Group, Providence/US
  • 16MD Anderson Cancer Center, Houston/US
  • 17Thomas Jefferson University Hospital, Philadelphia/US
  • 18Boston Medical Center, Boston/US



RTOG 0436 randomized patients (pts) undergoing non-operative management of esophageal carcinoma to concurrent chemoradiation with or without Cetuximab.


Pts with adenocarcinoma (AC) or squamous cell carcinoma (SCC) of the esophagus (EUS stage T1N1M0; T2-4 AnyN M0; AnyT/N M1a) were randomized to weekly concurrent paclitaxel (50 mg/m2), cisplatin (25 mg/m2) x 6 weeks, plus daily radiation 50.4 Gy/1.8 Gy fractions ± weekly cetuximab (400 mg/m2 day 1 then weekly 250 mg/m2 x 5). Stratification of patients was by histology, tumor size (< 5 cm vs >5 cm), and presence/absence of celiac lymph nodes. The primary endpoint was Overall Survival (OS). To detect an increase in 2-year OS from 41% to 53% with 80% power and a 1-sided 0.025 alpha, planned accrual was 420 pts. An interim analysis of endoscopic clinical complete response (cCR) was planned for the first 150 pts with each histology.


From 2008-2013 344 pts were accrued and 328 were eligible. Based on the interim analysis of cCR, the study stopped accruing AC pts in 5/2012. Based on reported data from the SCOPE-1 trial, SCC accrual stopped in 1/2013. Treatment arms were balanced for pretreatment characteristics: 80% T3/4 disease, 66% N1, and 19% had celiac nodes. Grade 3/4/5 treatment related AEs were 45%, 22%, 4% in Arm 1 (cetuximab) vs 49%, 17%, 1% in Arm 2 (no cetuximab). cCR rates were equivalent in arm 1 (56%) and arm 2 (59%, p = 0.72), with no differences seen by histology in arm 1 vs 2. For cCR pts, the 12 and 24 mo OS rates were 79% and 58% vs 53% & 30% for those with residual disease [p < 0.0001]. Median follow-up for all pts is 15.4 mos. The 12 and 24 mo OS (95% CI) were not different for Arm 1: 64% (56%, 71%), and 44% (36%, 52%), vs Arm 2: 65% (57%, 72%) and 42% (34%, 50%) [p = 0.70]. The 12 and 24 mo OS for AC (n= 203) was 65% and 43% for Arm 1 vs 64% and 41% for Arm 2 [p = 0.37]. For SCC (n = 125) there was also no difference in 12 and 24 mo OS: 62% and 46% for Arm 1 vs 67% and 43% for Arm 2 [p = 0.97].


The addition of cetuximab to concurrent chemoradiation failed to improve OS irrespective of tumor histology, and there were no differences in cCR rates by arm. These results add to the growing body of literature that, in an unselected patient population, there is no benefit for current EGFR targeted agents in the treatment of esophageal cancer. Biomarkers to better select patients for EGFR targeted therapy need to be identified. Supported by RTOG CA21661 & CCOP CA3742 NCI grants and Bristol Myers Squibb.