Randomized Phase II Trial of Carboplatin-Paclitaxel Compared with Carboplatin-Paclitaxel-Trastuzumab in Advanced (Stage III-IV) or Recurrent Uterine Serous Carcinomas that Overexpress Her2/Neu (NCT01367002): Updated Overall Survival Analysis.
Randomized Phase II Trial of Carboplatin-Paclitaxel Compared with Carboplatin-Paclitaxel-Trastuzumab in Advanced (Stage III-IV) or Recurrent Uterine Serous Carcinomas that Overexpress Her2/Neu (NCT01367002): Updated Overall Survival Analysis.
复制标题
DOI：
10.1158/1078-0432.ccr-20-0953
复制
发表时间：
2020-08-01
期刊：
影响因子：
--
通讯作者：
Santin AD
中科院分区：
文献类型：
--
作者：
Fader AN;Roque DM;Siegel E;Buza N;Hui P;Abdelghany O;Chambers S;Secord AA;Havrilesky L;O'Malley DM;Backes FJ;Nevadunsky N;Edraki B;Pikaart D;Lowery W;ElSahwi K;Celano P;Bellone S;Azodi M;Litkouhi B;Ratner E;Silasi DA;Schwartz PE;Santin AD
子宫浆液性癌(USC)是子宫内膜癌的侵袭性变种。根据多中心随机II期试验的初步结果，曲妥珠单抗(T)，一种针对Her2/Neu的人源化单抗，与卡铂/紫杉醇(C/P)相结合，被认为是治疗晚期/复发HER2/Neu阳性的USC的替代方案。我们报告了NCT01367002的最新生存分析。符合条件的患者有III-IV期或复发疾病。参与者以1：1的比例随机接受C/P治疗6个周期±T，然后是维持性T，直到病情进展或出现毒性。PFS是主要终点，OS和毒性是次要终点。61例患者被随机分为两组。经过25.9个月的中位随访，在58名可评估的患者中，有43人进展，38人死亡。更新的中位数-PFS继续偏爱T型臂，对照组和T型臂的中位数分别为8.0月和12.9个月，(HR 0.46，90%CI0.28-0.76；P=0.005)。41例初治的III-IV期患者中位PFS为9.3个月比17.7个月(HR0.44，90%CI0.23~0.83；P=0.015)；17例复发患者中位PFS为7.0月比9.2个月(HR0.12，90%CI0.03~0.48；P=0.004)。T组的OS高于对照组，中位数分别为29.6个月和24.4个月(HR0.58；90%CI0.34~0.99；P=0.046)。这一好处在III-IV期疾病患者中最为显著，T组患者的生存中位数未达到，而对照组为24.4个月(HR0.49，90%CI0.25-0.97；P=0.041)。毒性在不同的手臂上没有区别。对于晚期/复发HER2/Neu阳性的USC患者，在C/P基础上增加T可增加PFS和OS，在III-IV期疾病的治疗中获益最大。
Uterine-serous-carcinoma (USC) is an aggressive variant of endometrial cancer. Based on preliminary results of a multicenter, randomized phase II trial, trastuzumab (T), a humanized-monoclonal-antibody targeting Her2/Neu, in combination with carboplatin/paclitaxel (C/P), is recognized as an alternative in treating advanced/recurrent HER2/Neu-positive USC. We report the updated survival analysis of NCT01367002. Eligible patients had stage III-IV or recurrent-disease. Participants were randomized 1:1 to receive C/P for 6 cycles ± T followed by maintenance T until progression or toxicity. PFS was the primary-endpoint; OS and toxicity were secondary-endpoints. 61 patients were randomized. After a median-follow-up of 25.9-months, 43 progressions and 38 deaths occurred among 58 evaluable patients. Updated median-PFS continued to favor the T-arm, with medians of 8.0 versus 12.9-months in the control and T-arms, (HR 0.46, 90%CI 0.28–0.76; P=0.005). Median-PFS was 9.3 versus 17.7-months among 41 patients with stage III-IV disease undergoing primary treatment (HR 0.44, 90%CI 0.23–0.83; P=0.015), and 7.0 versus 9.2-months among 17 patients with recurrent disease (HR 0.12, 90%CI 0.03–0.48; P=0.004). OS was higher in the T compared to the control arm, with medians of 29.6 versus 24.4-months, (HR 0.58; 90%CI 0.34–0.99; P=0.046). The benefit was most notable in those with stage III-IV disease, with survival median not reached in the T-arm versus 24.4-months in the control arm (HR 0.49, 90%CI 0.25–0.97; P=0.041). Toxicity was not different between arms. Addition of T to C/P increased PFS and OS in women with advanced/recurrent HER2/Neu-positive USC, with the greatest benefit seen for the treatment of stage III-IV disease.