Resistance to novel androgen signaling inhibition and metastatic castration-resistant prostate cancer (mCRPC) progression is likely dependent on tumor microenvironment interactions. The Src pathway and neoangiogenesis have been implicated in prostate cancer progression. We studied the effect of adding the targeted agents dasatinib and sunitinib to abiraterone acetate (AA) in men with mCRPC.
In this open-label randomized phase 2 study, mCRPC patients received AA. At resistance to AA, they were randomized 1:1 to combination with dasatinib or sunitinib. At second progression, patients crossed over. The primary end point was time to treatment failure (TTF), defined as time to progression or death. Secondary end points included overall survival and safety.
From March 2011 to February 2015, a total of 179 patients were enrolled and 132 subsequently randomized. Median TTF was 5.7 months in the dasatinib group and 5.5 months in the sunitinib group. There was no difference between the two groups in terms of TTF (hazard ratio, 0.85; 95% confidence interval, 0.59-1.22). Median overall survival from study entry was 26.3 months in the dasatinib group and 27.7 months in the sunitinib group (hazard ratio, 1.02; 95% confidence interval, 0.71-1.47). Grade 3 or higher adverse events related to study medication were more frequent with sunitinib (n = 44, 46%) compared to dasatinib (n = 26, 24%). At data cutoff, 7 patients were experiencing a continuous response to AA, with a median duration of treatment of 5.7 years.
There is no difference in overall survival and TTF between dasatinib and sunitinib combined with abiraterone in the treatment of patients with bone mCRPC.
Clinical genitourinary cancer. 2020 May 30 [Epub ahead of print]
Nicholas Spetsieris, Myrto Boukovala, Justin A Weldon, Alexandros Tsikkinis, Anh Hoang, Ana Aparicio, Shi-Ming Tu, John C Araujo, Amado J Zurita, Paul G Corn, Lance Pagliaro, Jeri Kim, Jennifer Wang, Sumit K Subudhi, Nizar M Tannir, Christopher J Logothetis, Patricia Troncoso, Xuemei Wang, Sijin Wen, Eleni Efstathiou
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX., Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX., Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX., Department of Biostatistics, West Virginia University School of Public Health, Morgantown, WV., Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address: .