Tykerb gastric cancer – pro

Gastric cancer is known to have amplification of the ErbB2 (HER2) gene and Herceptin is supported for use in gastric cancer. Recently, there has been an interest in using Tyker(lapatinib) which is a drug that utalizes the same mechanism of action as Herceptin. One such trial is: LOGiC – Lapatinib Optimization Study in ErbB2 (HER2) Positive Gastric Cancer: A Phase III Global, Blinded Study Designed to Evaluate Clinical Endpoints and Safety of Chemotherapy Plus Lapatinib. This is an international multi-center trial that will enroll patients with locally advanced, unresectable, or metastatic gastric, esophageal, or gastro-esophageal junction cancer whose tumors have amplification of the ErbB2 (HER2) gene. The trial will investigate whether lapatinib, when added to the chemotherapy regimen, capecitabine plus oxaliplatin (CapeOx), extends the time to progression and overall survival. CapeOx is administered to all patients, and patients will be randomly assigned to receive either lapatinib or placebo. There is evidence of effectiveness for brian metastases, at least in breast cancer(Lin et al).

Iqbal et al showed that Tykerb is an effective first line drug. The evidence thus far suggests that the combination of lapatinib + capecitabine shows promising efficacy and is well tolerated as 1st line treatment for advanced GC(Pishvaian et al). The same appears to be true of paclitaxel and lapatinib and studies of this combination are ongoing.

A number of issues remain to study: the type of combination therapy, the role of Taykeb in patients previousely treated with Herceptin, and efficacy in brain mets of patients with gastric cancer.

 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) 22 (12): 2610-2615

Power, D. G., Kelsen, D. P & Shah, M. A. Advanced gastric cancer—slow but steady progress. Cancer Treat. Rev. 36, 384-392 (2010).

Ku, G. Y. & Ilson, D. H. Esophagogastric cancer: targeted agents. Cancer Treat. Rev. 36, 235-248 (2010).

Grothey, A. EGFR antibodies in colorectal cancer: where do they belong? J. Clin. Oncol. 28, 4668-4670 (2010).

M. Pishvaian, D. Sakaeva, R. K. Hsieh, S. Y. Rha, G. Caderillo-Ruiz, W. H. Miller Jr., A. M. Kemner, Y. M. Nagarwala, W. Zhang, H. Lenz; Georgetown University Medical Center, Washington, DC; Clinical Oncology Dispensary of the Republic of Bashkortostan, Ufa, Russia; Mackay Memorial Hospital, Taipei, Taiwan; Yonsei Cancer Center, Cancer Metastasis Research Center, Yonsei University College of Medicine, Seoul, South Korea; Deparment of Medical Oncology, Instituto Nacional de Cancerologia, Tlalpan, Mexico; Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, QC, Canada; GlaxoSmithKline, Collegeville, PA; University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA  A global, multicenter phase II trial of lapatinib plus capecitabine in gastric cancer. J Clin Oncol 29: 2011 (suppl 4; abstr 88)

Lin NU, Diéras V, Paul D, Lossignol D, Christodoulou C, Stemmler HJ, Roché H, Liu MC, Greil R, Ciruelos E, Loibl S, Gori S, Wardley A, Yardley D, Brufsky A, Blum JL, Rubin SD, Dharan B, Steplewski K, Zembryki D, Oliva C, Roychowdhury D, Paoletti P, Winer EP. Multicenter phase II study of lapatinib in patients with brain metastases from HER2-positive breast cancer. Clin Cancer Res. 2009 Feb 15;15(4):1452-9.

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