Tykerb with Herceptin – pro

Lapatinib is an oral receptor tyrosine kinase inhibitor, inhibiting both the ErbB-1 and ErbB-2 receptors. Lapatinib has been shown to have activity in ErbB-2–overexpressing breast cancer in several phase II and III clinical trials. Tykerb is approved with capecitabine or Femara.

Data from the first-ever randomized, multi-center, open label Phase III trial examining the combination of two targeted therapies, Tykerb™ (lapatinib ditosylate) tablets and Herceptin® (trastuzumab), in women with HER2-positive metastatic breast cancer was presented at the annual American Society of Clinical Oncology (ASCO) meeting in Chicago, in May 2008 and published in 2009. It randomized 296 patients to Tykerb plus Herceptin or Tykerb alone in the treatment of HER2-positive, recurrent breast cancer. Patients had received an average of four or five prior chemotherapy regimens and an average of three prior Herceptin-containing regimens for metastatic disease, with a median time from the last Herceptin regimen being approximately 25 days. Nearly half of all patients were hormone-positive. Patients were randomized to Tykerb (1,500 mg/day) or Tykerb (1,000 mg/day) plus Herceptin (4 mg/kg loading dose followed by 2 mg/kg per week).

•Women treated with a combination of Tykerb and Herceptin remained free of cancer progression for roughly one month longer than women treated with Tykerb alone (12.0 weeks versus 8.1 weeks).
•Overall survival was roughly three months longer among women treated with Tykerb and Herceptin than among women treated with Tykerb alone (51.6 weeks versus 39 weeks). The difference between groups in overall survival was not statistically significant, however, suggesting that it could have occurred by chance alone.
•Women treated with Tykerb and Herceptin were more likely to experience diarrhea than women treated with Tykerb alone.
These results suggest that the combination of Tykerb and Herceptin more effectively delays cancer progression than Tykerb alone.

A recent review from The UK National Techology Assessment concluded that either trastuzumab with an aromatase inhibitor(AI) or lapatinib  with an AI were not superior to AI alone. The same would presumably apply to the combination the two with an AI.

Fleeman N, Bagust A, Boland A, Dickson R, Dundar Y, Moonan M, Oyee J, Blundell M, Davis H, Armstrong A, Thorp N.Lapatinib and trastuzumab in combination with an aromatase inhibitor for the first-line treatment of metastatic hormone receptor-positive breast cancer which over-expresses human epidermal growth factor 2 (HER2): a systematic review and economic analysis.
Health Technol Assess. 2011;15(42):1-93,.

UBlackwell KL, Burstein HJ, Storniolo AM et al. Randomized study of lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer. Journal of Clinical Oncology. 2010;28:1124-1130.

Gomez HL, Chavez MA, Doval DC et al. A phase II, randomized trial using the small molecule tyrosine kinase inhibitor lapatinib as a first-line treatment in patients with FISH positive advanced or metastatic breast cancer. J Clin Oncol 2005;23(suppl 16):203S.

Trudeau M, Johnston S, Kaufman et al. Lapatinib (Tycerb) monotherapy in patients with recurrent inflammatory breast cancer (IBC): Clinical activity and biologic predictors of response. Ann Oncol 2006;17(suppl 9):ix69

O’Shaughnessy J, Blackwell KL, Burstein H, et al. A randomized study of lapatinib alone or in combination with trastuzumab in heavily pretreated HER2+ metastatic breast cancer progressing on trastuzumab therapy. Program and abstracts of the 44th American Society of Clinical Oncology Annual Meeting; May 30 – June 3, 2008; Chicago, Illinois. Abstract 1015


José Baselga et al, Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet Volume 379, No. 9816, p633–640, 18 February 2012

NCCN, Breast Cancer 2016

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