Phase II trial of lapatinib shows some activity in CRPC

Lapatinib — which is already approved for the treatment of selected patients with advanced breast cancer — is an oral inhibitor of epidermal growth factor receptor (EGFR) and HER-2 tyrosine kinases, both of which may be relevant to activation of the androgen receptor and therefore may be involved in the progression of advanced forms of prostate cancer.

Whang et al. have just published data from a small, Phase II clinical trial of lapatinib in the therapy of castration-resistant prostate cancer (CRPC). In this multi-center, open-label study, chemotherapy-naïve men with a rising PSA on treatment with androgen deprivation therapy were treated with lapatinib 1,500 mg once a day.

The key results of this study are as follows:

  • A total of 29 patients were enrolled.
  • The average (median) age of the patients was 73 years.
  • The patients’ average (median) baseline PSA level was 21.6 ng/ml.
  • 7/29 men (24 percent) had no radiologic evidence of metastatic disease.
  • 22/29 men (76 percent) had evident bone metastasis or measurable disease or both.
  • Treatment was well tolerated and grade 3 treatment-related toxicities were limited to diarrhea (14 percent) and rash (3 percent).
  • 1/21 evaluable patients showed a >50 percent reduction in PSA from baseline.
  • Another patient had a 47 percent reduction in PSA from baseline and an ongoing duration of response of 45+ months.
  • The average (median) time to PSA progression was 29 days.

It appears that lapatinib has some degree of single-agent activity in a subset of patients with CRPC. If lapatinib is going to have real clinical value in the treatment of CRPC, however, it will be important to be able to identify markers that are expressed those patients most likely to respond to lapatinib.

Lapatinib is already marketed in many countries around the world (as Tykerb® or Tyverb®) by GlaxoSmithKline.

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