Lapatinib in combination with capecitabine plus oxaliplatin (CapeOx) in HER2-positive advanced or metastatic gastric, esophageal, or gastroesophageal adenocarcinoma (AC): The TRIO-013/LOGiC Trial.

Gastrointestinal (Noncolorectal) Cancer
Session Type and Session Title: 
Oral Abstract Session, Gastrointestinal (Noncolorectal) Cancer
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr LBA4001)
J. Randolph Hecht, Yung-Jue Bang, Shukui Qin, Hyun-Chul Chung, Jian-Ming Xu, Joon Oh Park, Krzysztof Jeziorski, Yaroslav Shparyk, Paulo M. Hoff, Alberto F. Sobrero, Pamela Salman, Jin Li, Svetlana Protsenko, Marc E. Buyse, Karen Afenjar, Tomomi Kaneko, Allison Kemner, Sergio Santillana, Michael F. Press, Dennis J. Slamon; David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA; Seoul National University Hospital, Seoul, South Korea; Nanjing Yanggongjing Hospital, Nanjing, China; Yonsei University College of Medicine Severance Hospital, Yonsei, South Korea; Cancer Center, 307 Hospital, Academy of Military Medical Science, Beijing, China; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland; Lviv State Oncology Regional Treatment and Diagnostic Centre, Lviv, Ukraine; Instituto do Cancer do Estado de São Paulo, São Paulo, Brazil; Azienda Ospedaliera Universitaria San Martino, Genova, Italy; Fundación Arturo López Pérez, Santiago, Chile; Fudan University Shanghai Cancer Center, Shanghai, China; N. N. Petrov Research Institute of Oncology, St. Petersburg, Russia; International Drug Development Institute, Louvain la Neuve, Belgium; Cancer International Research Group, Paris, France; GlaxoSmithKline, Uxbridge, United Kingdom; GlaxoSmithKline, Collegeville, PA, United Kingdom; GlaxoSmithKline, Rio de Janeiro, Brazil; USC Norris Comprehensive Cancer Center, Los Angeles, CA; University of California, Los Angeles, School of Medicine/Translational Oncology Research Laboratory, Los Angeles, CA

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures


Background: HER2 amplification is common in upper GI tract (UGIT) adenocarcinomas and inhibition improves clinical outcomes. Lapatinib ditosylate (L), a dual anti EGFR and anti HER2 tyrosine kinase inhibitor with preclinical activity against these cancers, was investigated in a phase III, randomized, double blind trial evaluating efficacy and safety in combination with CapeOx as first-line treatment of advanced or metastatic HER2+ UGIT ACs. Methods: Subjects had measurable and/or non-measurable disease with overexpression or amplification of HER2 (IHC2+ and FISH amplified, or IHC 3+, or FISH, CISH, or SISH amplified). HER2 status was reviewed by the central lab. Subjects were randomized 1:1 to CapeOx q3w (oxaliplatin 130mg/m2 day 1; capecitabine 850mg/m2/BID days 1 – 14), and daily L (1250mg) (CapeOx+L) or placebo (CapeOx+P). The primary efficacy population (PEP) comprised all subjects whose tumors were centrally confirmed to be FISH amplified. The primary endpoint was overall survival (OS) of the PEP. Secondary endpoints included progression free survival (PFS), overall response rate (ORR) and safety. Results: 545 pts were randomized and 487 had HER2+ centrally confirmed. The primary endpoint was not reached with a hazard ratio (HR) for OS of CapeOx+L compared to CapeOx+P of 0.91 (95% CI 0.73, 1.12, p=0.35); median 12.2 vs. 10.5 months, respectively. HR for uncensored PFS was 0.86 (95% CI 0.71 - 1.04, p=0.10); median 6.0 vs. 5.4 months. The analysis of PFS censored by the time of subsequent anticancer therapy as per protocol showed a HR of 0.82 (95% CI 0.68, 1.00, p=0.04). ORR was 53% in the CapeOx+L arm and 40% in the CapeOx+P arm. Pre-specified subgroup analyses showed significant improvements in OS in Asian pts (HR= 0.68) and those under 60 years (HR=0.69). There was no association between IHC and OS. Toxicity profiles were similar except for increased overall diarrhea, and skin toxicity and grade 3+ diarrhea (12 vs 3%) with CapeOx+L. Conclusions: The addition of L to CapeOx did not reach its primary endpoint, though certain subgroups showed improvement. Further clinical and molecular analyses will be presented. Clinical trial information: NCT00680901.