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.
Clin Genitourin Cancer. 2021 Feb;19(1):22-31.e5. doi: 10.1016/j.clgc.2020.05.013. Epub 2020 May 30.
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.
新型雄激素信号抑制和转移性去势抵抗性前列腺癌（mCRPC）进展的耐药性可能依赖于肿瘤微环境的相互作用。Src 通路和新生血管生成与前列腺癌的进展有关。我们研究了在 mCRPC 患者中添加靶向药物 dasatinib 和 sunitinib 与 abiraterone acetate（AA）联合治疗的效果。
在这项开放标签的随机 2 期研究中，mCRPC 患者接受 AA 治疗。在 AA 耐药后，他们按 1:1 随机分为联合 dasatinib 或 sunitinib 组。第二次进展时，患者交叉。主要终点是治疗失败时间（TTF），定义为进展或死亡时间。次要终点包括总生存期和安全性。
从 2011 年 3 月到 2015 年 2 月，共纳入 179 例患者，其中 132 例随后被随机分组。Dasatinib 组 TTF 的中位数为 5.7 个月，sunitinib 组为 5.5 个月。两组 TTF 无差异（危险比，0.85；95%置信区间，0.59-1.22）。从研究入组开始，Dasatinib 组的中位总生存期为 26.3 个月，sunitinib 组为 27.7 个月（危险比，1.02；95%置信区间，0.71-1.47）。与研究药物相关的 3 级或更高不良事件在 sunitinib 组更为常见（n=44，46%），而 dasatinib 组为 26（24%）。在数据截止时，7 例患者对 AA 持续有反应，中位治疗时间为 5.7 年。
在治疗骨转移的 mCRPC 患者中，与 abiraterone 联合使用 dasatinib 和 sunitinib 对总生存期和 TTF 没有差异。
