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Phase II trial of lapatinib in patients in stage D0 prostate cancer (E5803): Effect of Kras and EGFR status on clinical outcome
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Phase II trial of lapatinib in patients in stage D0 prostate cancer (E5803): Effect of Kras and EGFR status on clinical outcome

Y. Chen, J. Kolesar, W. Huang, R. S. DiPaola, M. Pins, M. A. Carducci, M. N. Stein, G. Bubley, G. Wilding and G. Liu
Journal of clinical oncology, Vol.28(15_suppl), pp.4668-4668
05/20/2010
DOI: 10.1200/jco.2010.28.15_suppl.4668
url
https://doi.org/10.1200/jco.2010.28.15_suppl.4668View
Published (Version of record) Open Access

Abstract

Abstract only Background: Activation of epidermal growth factor is important in prostate cancer (PC) development and the transcription of androgen receptor regulated genes. Lapatinib is a selective dual tyrosine kinase inhibitor of EGFR and ErbB2. Here we report the effects of Kras 38 mutation, EGFR expression/mutation, and drug metabolizing enzyme polymorphisms on clinical outcome. Methods: Patients (pts) with rising PSA after primary therapy for PC were enrolled. A PSA doubling time (PSADT) of ≤ 12 months was required (calculated from a minimum of 3 PSA obtained at least 6 weeks apart, within 6 months of enrollment). No radiographic evidence of metastasis was allowed. Lapatinib was administered orally at 1,500 mg once daily. Primary tumor blocks were obtained and assessed for EGFR expression, EGFR Q787Q polymorphism, and Kras 38 mutational status. Drug metabolizing enzyme single-nucleotide polymorphism was assessed in PBMCs. Results: 49 pts were enrolled (14 ineligible), resulting in 35 pts for analysis. Of these, 14 tumor blocks and 29 whole blood samples were available. High EGFR expression (using AQUA) was seen in 4 pts (low EGFR expression in 10) and Kras 38 mutation present in 3 of 13 evaluable samples. No PSA response was observed; however, 28 (80.0%) maintained stable disease. Pre-treatment average slope was 0.19 log PSA/month (PSADT=3.70 months), in contrast to on-treatment average slope of 0.13 log PSA/month (PSADT=5.44 months) using linear mixed effects models (p = 0.006). Median progression-free survival was 17.4 months for the high EGFR group and 6.0 months for the low EGFR group (p = 0.50). Pts with Kras 38 mutation had shorter PFS than those without Kras 38 mutation, but the difference was not statistically significant (p = 0.09). No association between SNPs and drug toxicity was found. Conclusions: Although no PSA responses were observed, lapatinib may have biologic activity in men with androgen-dependent PC as evidenced by a decrease in PSA slope in this nonrandomized study. Trends towards improved PFS in pts with EGFR overexpression and Kras wild type status support that a biologic effect is present in this patient population and that further trials using lapatinib in pre-castrate PC warranted.

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