Tykerb (lapatinib) and chemo for Gastric Cancer – pro

20% of patients with advanced gastric cancer overexpress human epidermal growth-factor receptor 2 (HER2), and these patients had significantly improved overall survival when trastuzumab (Herceptin) is added to chemotherapy, compared with chemotherapy alone. In a study presented in 2009 ASCO, the improvement in overall survival was 2.7 months, from 11.1 months in the chemotherapy group to 13.8 months in the trastuzumab group (hazard ratio, 0.74, P = .0046). SImilar results were shown by ToGA, a large international Phase III trial investigating the benefit of Herceptin as the first therapy for patients with advanced and inoperable stomach cancer (first line).
This greatly increased and interest in Tykerb for gastric cancer. Preclinical studies in gastric cancer have shown that the drug has concentration-dependant antiproliferative properties against HER2-positive gastric cancer cell lines, showing synergy with trastuzumab.This agent is under study alone and combinations. A recent study by Iqbal concluded that Lapatinib is well tolerated, with modest single-agent activity in advanced/metastatic gastric cancer patients.

The study by Stath et al conlcuded that Lapatinib plus paclitaxel demonstrated activity in the second-line treatment of patients with HER2 FISH-positive IHC3+ advanced gastric cancer but did not significantly improve OS in the intent-to-treat population.

A recent editorial by Berman Schulze concluded: ” Lapatinib seems to be suitable especially for a subset of patients (i.e., <60 years of age and Asian origin). Resistance mechanisms against lapatinib have been reported and might be overcome by adding further targeted therapies to HER2-antagonizing combination therapies. In contrast to breast cancer, HER2-targeting in gastric adenocarcinoma seems to be more challenging. ”
Kazuhiro Nishikawa et al, Phase II study of the effectiveness and safety of trastuzumab and paclitaxel for taxane‐ and trastuzumab‐naïve patients with HER2‐positive, previously treated, advanced, or recurrent gastric cancer (JFMC45‐1102)Int J Cancer. 2017 Jan 1; 140(1): 188–196.

Arik Bernard Schulze, Andrea Kerkhoff, Georg Lenz, Torsten Kessle et lal, rTargeted therapies of HER2-positive gastric adenocarcinoma. TCR Vol 6, Supplement 7 (October 2017):
Satoh T et al, Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2-amplified advanced gastric cancer in Asian populations: TyTAN–a randomized, phase III study.J Clin Oncol. 2014 Jul 1;32(19):2039-49.
Van Cutsem E, Kang Y, Chung H et al. Efficacy results from the ToGA trial: a Phase III study of trastuzumab added to standard chemotherapy (CT) in first-line human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (GC). Presented at the 2009 annual meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL. Abstract LBA4509.

Y. Kang, Y. Bang, F. Lordick, S. Park, A. Sawaki, H. Chung, L. Shen, J. M. Xu, J. Leon-Chong, E. Van Cutsem Incidence of gastric and gastro-esophageal cancer in the ToGA trial: Correlation with HER2 positivity 2008 Gastrointestinal Cancers Symposium , Ab. 11

S. Iqbal et al, Southwest Oncology Group study S0413: a phase II trial of lapatinib (GW572016) as first-line therapy in patients with advanced or metastatic gastric cancer Ann Oncol (2011)
doi: 10.1093/annonc/mdr021

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