Abstract
Trastuzumab with trimodality treatment for esophageal adenocarcinoma with HER2 overexpression: NRG Oncology/RTOG 1010
Journal of clinical oncology, Vol.38(15_suppl), pp.4500-4500
05/20/2020
DOI: 10.1200/JCO.2020.38.15_suppl.4500
Abstract
4500
Background: Trastuzumab is a monoclonal antibody against human epidermal growth factor receptor 2 (HER2). The primary objective of RTOG 1010 was to determine if trastuzumab increases disease-free survival (DFS) when combined with trimodality treatment for patients with HER2 overexpressing esophageal adenocarcinoma. Methods: This open label, randomized phase III trial included patients with newly diagnosed stage T1N1-2, T2-3N0-2 adenocarcinoma of the esophagus involving the mid, distal, or esophagogastric junction and up to 5cm of the stomach. All patients received chemotherapy (C) of paclitaxel, 50mg/m
2
and carboplatin AUC = 2, weekly for 6 weeks, with radiation (XRT: 3D-CRT or IMRT, 50.4 Gy in 28 fractions) followed by surgery. Patients were randomized 1:1 to receive weekly trastuzumab 4mg/kg week 1 then 2mg/kg/weekly x 5 during CXRT then 6 mg/kg for 1 dose prior to surgery and 6mg/kg every 3 weeks for 13 treatments after surgery. HER2 status was determined by IHC and gene amplification by FISH. With a 2-sided alpha of 0.05, 162 DFS events provide 90% power to detect a signal for an increase in median DFS from 15 to 25 months. DFS and overall survival (OS) were estimated by the Kaplan-Meier method. and arms were compared using the log rank test. The Cox proportional hazards model was used to analyze treatment effect. Results: 571 patients were entered for assessment of HER2 expression, 203 HER2+ patients randomized. The median follow-up for alive patients is 5.0 years. The estimated 2, 3, and 4-year DFS (95% CI) for the CXRT +trastuzumab arm were 41.8% (31.8%, 51.7%), 34.3% (24.7%, 43.9%), and 33.1% (23.6%, 42.7%), respectively, and for the CXRT arm were 40.0% (30.0%, 49.9%), 33.4% (23.8%, 43.0%), and 30.1% (20.7%, 39.4%), respectively; log-rank p = 0.85. The median DFS time is 19.6 months (13.5-26.2) for the CXRT +trastuzumab arm compared to 14.2 months (10.5-23.0) for the CXRT arm. The hazard ratio (95% CI) comparing the DFS of CXRT+trastuzumab arm to the CXRT arm was 0.97 (0.69, 1.36). The median OS time was 38.5 months (26.2-70.4) for the CXRT+trastuzumab arm compared to 38.9 months (29.0-64.5) for the CXRT arm, hazard ratio (95% CI): 1.01 (0.69, 1.47). There was no statistically significant increase in treatment-related toxicities with the addition of trastuzumab including no increase in cardiac events. Conclusions: The addition of trastuzumab to trimodality treatment did not improve DFS for patients with HER2 overexpressing esophageal adenocarcinoma. Supported by NCI grants U10CA180868, UG1CA189867, U10CA180822 and Genentech. Clinical trial information: NCT01196390 .
Details
- Title: Subtitle
- Trastuzumab with trimodality treatment for esophageal adenocarcinoma with HER2 overexpression: NRG Oncology/RTOG 1010
- Creators
- Howard Safran - Brown University Oncology Research Group, Providence, RIKathryn A. Winter - Statistical Center, Radiation Therapy Oncology Group, Philadelphia, PADennis A. Wigle - Mayo Clinic, Rochester, MNThomas A. DiPetrillo - Rhode Island Hospital, Providence, RIMichael G. Haddock - Mayo Clinic, Rochester, MNTheodore S. Hong - Department of Radiation Oncology, Massachusetts General Hospital, Boston, MALawrence P. Leichman - Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, NYLakshmi Rajdev - Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NYMurray B. Resnick - Rhode Island Hospital, Providence, RILisa A. Kachnic - Boston Medical Center, Boston, MASamantha A. Seaward - Kaiser Permanente, Santa Clara, CAHarvey J. Mamon - Dana-Farber Cancer Institute, Boston, MADayssy Alexandra Diaz Pardo - The Ohio State University, Columbus, OHCarryn M. Anderson - University of IowaXinglei Shen - University of Kansas Cancer Center, Westwood, KSAnand K. Sharma - Medical University of South Carolina, Charleston, SCAlan W. Katz - University of Rochester, James P. Wilmot Cancer Institute, Rochester, NYJonathan C. Salo - Levine Cancer Institute, Atrium Health, Charlotte, NCKara Lynne Leonard - Rhode Island Hospital, Providence, RIChristopher H. Crane - The University of Texas MD Anderson Cancer Center, Houston, TX
- Resource Type
- Abstract
- Publication Details
- Journal of clinical oncology, Vol.38(15_suppl), pp.4500-4500
- DOI
- 10.1200/JCO.2020.38.15_suppl.4500
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Grant note
- DOI: 10.13039/100000002, name: U.S. National Institutes of Health; name: Pharmaceutical/Biotech Company
- Language
- English
- Date published
- 05/20/2020
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984315658902771
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