Memorial Sloan Kettering Cancer Center, New York, New York.
Beth Israel Deaconess Medical Center, Boston, Massachusetts.
Cancer. 2019 Jul 15;125(14):2400-2408. doi: 10.1002/cncr.32061. Epub 2019 Apr 5.
In a prior open-label study, the combination of dalantercept, a novel antiangiogenic targeting activin receptor-like kinase 1 (ALK1), plus axitinib was deemed safe and tolerable with a promising efficacy signal in patients with advanced renal cell carcinoma (RCC).
In the current phase 2, randomized, double-blind, placebo-controlled study, patients with clear cell RCC previously treated with 1 prior angiogenesis inhibitor were randomized 1:1 to receive axitinib plus dalantercept versus axitinib plus placebo. Randomization was stratified by the type of prior therapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints were PFS in patients with ≥2 prior lines of anticancer therapy, overall survival, and the objective response rate.
Between June 10, 2014, and February 23, 2017, a total of 124 patients were randomly assigned to receive axitinib plus dalantercept (59 patients) or placebo (65 patients). The median PFS was not found to be significantly different between the treatment groups (median, 6.8 months vs 5.6 months; hazard ratio, 1.11 [95% CI, 0.71-1.73; P = .670]). Neither group reached the median overall survival (hazard ratio, 1.39 [95% CI, 0.70-2.77; P = .349]). The objective response rate was 19.0% (11 of 58 patients; 95% CI, 9.9%-31.4%) in the dalantercept plus axitinib group and 24.6% (15 of 61 patients; 95% CI, 14.5%-37.3%) in the placebo plus axitinib group. At least 1 treatment-emergent adverse event of ≥grade 3 was observed in 59% of patients (34 of 58 patients) in the dalantercept group and 64% of patients (39 of 61 patients) in the placebo group. One treatment-related death occurred in the placebo plus axitinib group.
Although well tolerated, the addition of dalantercept to axitinib did not appear to improve treatment-related outcomes in previously treated patients with advanced RCC.
在一项先前的开放标签研究中，新型抗血管生成靶向激活素受体样激酶 1（ALK1）的dalantercept与 axitinib 联合使用，在先前接受过 1 种血管生成抑制剂治疗的晚期肾细胞癌（RCC）患者中被认为是安全且耐受良好的，并且具有有希望的疗效信号。
在当前的 2 期、随机、双盲、安慰剂对照研究中，先前接受过 1 种抗血管生成治疗的透明细胞 RCC 患者按 1:1 随机分配接受 axitinib 加 dalantercept 或 axitinib 加安慰剂治疗。随机分组按先前治疗的类型进行分层。主要终点是无进展生存期（PFS）。次要终点是在接受≥2 线抗癌治疗的患者中的 PFS、总生存期和客观缓解率。
2014 年 6 月 10 日至 2017 年 2 月 23 日期间，共有 124 名患者被随机分配接受 axitinib 加 dalantercept（59 名患者）或安慰剂（65 名患者）治疗。未发现治疗组之间的中位 PFS 有显著差异（中位值，6.8 个月比 5.6 个月；风险比，1.11 [95%CI，0.71-1.73；P=0.670]）。两组均未达到中位总生存期（风险比，1.39 [95%CI，0.70-2.77；P=0.349]）。客观缓解率在 dalantercept 加 axitinib 组为 19.0%（58 例患者中有 11 例；95%CI，9.9%-31.4%），安慰剂加 axitinib 组为 24.6%（61 例患者中有 15 例；95%CI，14.5%-37.3%）。dalantercept 组中至少有 1 例治疗后出现≥3 级的不良事件的患者占 59%（58 例患者中有 34 例），安慰剂组中这一比例为 64%（61 例患者中有 39 例）。安慰剂加 axitinib 组有 1 例治疗相关死亡。
尽管耐受良好，但在先前接受过治疗的晚期 RCC 患者中，添加 dalantercept 似乎并未改善治疗相关结局。
