TY - JOUR
T1 - A Phase 2 Trial of Abiraterone Followed by Randomization to Addition of Dasatinib or Sunitinib in Men With Metastatic Castration-Resistant Prostate Cancer
AU - Spetsieris, Nicholas
AU - Boukovala, Myrto
AU - Weldon, Justin A.
AU - Tsikkinis, Alexandros
AU - Hoang, Anh
AU - Aparicio, Ana
AU - Tu, Shi Ming
AU - Araujo, John C.
AU - Zurita, Amado J.
AU - Corn, Paul G.
AU - Pagliaro, Lance
AU - Kim, Jeri
AU - Wang, Jennifer
AU - Subudhi, Sumit K.
AU - Tannir, Nizar M.
AU - Logothetis, Christopher J.
AU - Troncoso, Patricia
AU - Wang, Xuemei
AU - Wen, Sijin
AU - Efstathiou, Eleni
N1 - Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2021/2
Y1 - 2021/2
N2 - Background: 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. Patients and Methods: 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. Results: 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. Conclusion: There is no difference in overall survival and TTF between dasatinib and sunitinib combined with abiraterone in the treatment of patients with bone mCRPC.
AB - Background: 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. Patients and Methods: 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. Results: 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. Conclusion: There is no difference in overall survival and TTF between dasatinib and sunitinib combined with abiraterone in the treatment of patients with bone mCRPC.
KW - Androgen-signaling inhibition
KW - Neoangiogenesis
KW - Src pathway
KW - Targeted agents
KW - Tumor microenvironment
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U2 - 10.1016/j.clgc.2020.05.013
DO - 10.1016/j.clgc.2020.05.013
M3 - Article
C2 - 32675015
AN - SCOPUS:85087803956
SN - 1558-7673
VL - 19
SP - 22-31.e5
JO - Clinical Genitourinary Cancer
JF - Clinical Genitourinary Cancer
IS - 1
ER -