Abstract No.: 16037
Citation: J Clin Oncol 26:
2008 (May 20 suppl; abstr 16037)
Author(s):
Y. E. Whang, C. N. Moore, A. J. Armstrong, W. K. Rathmell, P. A. Godley, J. M. Crane, G. I. Grigson, K. Morris, C. P. Watkins, D. J. George
Background: Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) tyrosine kinases represent potential targets in prostate cancer. HER2 promotes progression of prostate cancer to the hormone refractory stage and ligand-independent activation of androgen receptor in preclinical models. Inactivation of HER2 leads to inhibition of androgen receptor transcriptional activity and decreased synthesis of prostate specific antigen (PSA). Lapatinib (GW57206) is a tyrosine kinase inhibitor of EGFR and HER2.
Methods: In this multicenter, open-label trial, patients with rising PSA on androgen deprivation therapy who completed antiandrogen withdrawal, if previously on antiandrogen, and have not received chemotherapy were eligible. They were treated with lapatinib at an oral dose of 1500 mg daily. The primary endpoints were to determine PSA response rates and time to PSA progression.
Results: Twenty-nine patients enrolled on the study had a median age of 72.5 years (range 58-91 y) and a baseline PSA of 21.6 (4.5-196.5). Six patients had no radiologic evidence of metastatic disease while the remaining patients had bone or measurable disease or both. The most frequent adverse events were diarrhea (76%), fatigue (72%), rash (41 %) and anemia (38%). Dyspepsia, anorexia, and nausea were less frequently noted. Grade 3 treatment-related toxicities were diarrhea (17%) and rash (3%) that led to discontinuation in one patient for rash and dose interruption/reduction for diarrhea. One of 21 evaluable patients had >50% reduction in PSA (197 to 49), while another patient had 47% reduction in PSA (12.9 to 6.9), with a duration of response of >15 months. The median time to PSA progression was 29 days. Two patients had nonprogressive disease lasting >15 and >5 months.
Conclusions:
Lapatinib was well tolerated. Lapatinib showed single agent activity in a small subset of unselected patients with hormone refractory prostate cancer, as measured by PSA. Future trials should incorporate predictive biomarkers and a combination with other agents.