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.
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NCCN, Breast Cancer 2016