OBJECTIVES: Epidermal growth factor receptor (EGFR) and HER-2 tyrosine kinases may be involved in activation of androgen receptor and progression of prostate cancer. They represent potential therapeutic targets in prostate cancer. Lapatinib is an oral inhibitor of EGFR and HER-2. The objective of this study is to assess the preliminary clinical efficacy of lapatinib in the therapy of castration-resistant prostate cancer. METHODS: In this multicenter, open-label trial, patients with rising PSA on androgen deprivation therapy and not having received chemotherapy were eligible. They were treated with lapatinib at a dose of 1,500 mg once daily. The primary end point was a >50% confirmed PSA decline from baseline; safety, tolerability, and time to PSA progression were secondary outcomes. RESULTS: Twenty-nine patients enrolled in the study had a median age of 73 years and a baseline PSA of 21.6 ng/ml. Seven patients had no radiologic evidence of metastatic disease, while the remaining patients had bone or measurable disease or both. Treatment was well tolerated with only grade 3 treatment-related toxicities being diarrhea (14%) and rash (3%). One of 21 evaluable patients had >50% reduction in PSA, while another patient had 47% reduction in PSA with an ongoing duration of response of 45+ months. The median time to PSA progression was 29 days. CONCLUSIONS: Lapatinib showed single agent activity in a small subset of unselected patients with castration-resistant prostate cancer, as measured by PSA. Future trials should explore a trial design with time-to-event end points and predictive biomarkers and a combination with other agents.
OBJECTIVES:Epidermal growth factor receptor (EGFR) and HER-2 tyrosine kinases may be involved in activation of androgen receptor and progression of prostate cancer. They represent potential therapeutic targets in prostate cancer. Lapatinib is an oral inhibitor of EGFR and HER-2. The objective of this study is to assess the preliminary clinical efficacy of lapatinib in the therapy of castration-resistant prostate cancer. METHODS: In this multicenter, open-label trial, patients with rising PSA on androgen deprivation therapy and not having received chemotherapy were eligible. They were treated with lapatinib at a dose of 1,500 mg once daily. The primary end point was a >50% confirmed PSA decline from baseline; safety, tolerability, and time to PSA progression were secondary outcomes. RESULTS: Twenty-nine patients enrolled in the study had a median age of 73 years and a baseline PSA of 21.6 ng/ml. Seven patients had no radiologic evidence of metastatic disease, while the remaining patients had bone or measurable disease or both. Treatment was well tolerated with only grade 3 treatment-related toxicities being diarrhea (14%) and rash (3%). One of 21 evaluable patients had >50% reduction in PSA, while another patient had 47% reduction in PSA with an ongoing duration of response of 45+ months. The median time to PSA progression was 29 days. CONCLUSIONS:Lapatinib showed single agent activity in a small subset of unselected patients with castration-resistant prostate cancer, as measured by PSA. Future trials should explore a trial design with time-to-event end points and predictive biomarkers and a combination with other agents.
Authors: Stefan Vallo; Jens Mani; Matthias Stastny; Jasmina Makarević; Eva Juengel; Igor Tsaur; Georg Bartsch; Axel Haferkamp; Roman A Blaheta Journal: Invest New Drugs Date: 2012-07-17 Impact factor: 3.850
Authors: Atish D Choudhury; Anna C Schinzel; Maura B Cotter; Rosina T Lis; Katherine Labella; Ying Jie Lock; Francesca Izzo; Isil Guney; Michaela Bowden; Yvonne Y Li; Jinal Patel; Emily Hartman; Steven A Carr; Monica Schenone; Jacob D Jaffe; Philip W Kantoff; Peter S Hammerman; William C Hahn Journal: Cancer Res Date: 2016-11-29 Impact factor: 12.701
Authors: Kwanghee Kim; Philip A Watson; Souhil Lebdai; Sylvia Jebiwott; Alexander J Somma; Stephen La Rosa; Dipti Mehta; Katie S Murray; Hans Lilja; David Ulmert; Sebastien Monette; Avigdor Scherz; Jonathan A Coleman Journal: Clin Cancer Res Date: 2018-02-20 Impact factor: 12.531
Authors: Shuai Gao; Huihui Ye; Sean Gerrin; Hongyun Wang; Ankur Sharma; Sen Chen; Akash Patnaik; Adam G Sowalsky; Olga Voznesensky; Wanting Han; Ziyang Yu; Elahe A Mostaghel; Peter S Nelson; Mary-Ellen Taplin; Steven P Balk; Changmeng Cai Journal: Clin Cancer Res Date: 2016-03-02 Impact factor: 12.531