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. Specifically, lapatinib is effective in patients with metastatic breast cancer, with inflammatory breast cancer, and possibly, with brain metastases. An ongoing clinical trial and another anticipated clinical trial will investigate lapatinib as adjuvant treatment in early-stage disease. One such trial is: Neo ALTTO (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimisation) Study, NCT00553358
This is a randomised, open label multicenter Phase III study comparing the efficacy of neoadjuvant lapatinib plus paclitaxel, versus trastuzumab plus paclitaxel, versus concomitant lapatinib and trastuzumab plus paclitaxel given as neoadjuvant treatment in HER2/ErbB2 over-expressing and/or amplified primary breast cancer. Patients will be randomised to receive either: lapatinib 1500 mg daily, trastuzumab 4 mg/kg iv load followed by 2 mg/kg iv weekly, or lapatinib 1000 mg daily with trastuzumab 4 mg/kg iv load followed by 2 mg/kg iv weekly for a total of 6 weeks. After this biological window, patients on monotherapy arms will continue on the same targeted therapy plus weekly paclitaxel 80 mg/m2 for a further 12 weeks, up to definitive surgery. In the combination arm, patients will receive lapatinib 750 mg daily in combination with trastuzumab 2 mg/kg IV plus weekly paclitaxel 80mg/m2 IV for a further 12 weeks, up to definitive surgery. After surgery, patients will receive three courses of adjuvant chemotherapy with FEC followed by the same targeted therapy as in the biological window of the neoadjuvant setting for a further 34 weeks (in the combination arm, lapatinib dose will be 1000 mg daily in combination with trastuzumab). The planned total duration of the anti-HER2 therapy will be one year. Of concern, in teh similar but adjuvant ALTTO trial, Arm 2 was discontinued in 2011 becasue Tykerb appeared less active at the interim analysis. The data looked at in the interim analysis show that lapatinib (Arm 2 of ALTTO) does not appear to be as good as standard trastuzumab in preventing disease recurrence, according to the IDMC.
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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