随机 II 期临床试验：卡铂-紫杉醇与卡铂-紫杉醇-曲妥珠单抗治疗过度表达 Her2/Neu（NCT01367002）的晚期（III-IV 期）或复发性子宫浆液性癌：总生存分析更新。
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.
机构信息
John Hopkins School of Medicine, Baltimore, Maryland.
University of Maryland, Baltimore, Maryland.
出版信息
Clin Cancer Res. 2020 Aug 1;26(15):3928-3935. doi: 10.1158/1078-0432.CCR-20-0953. Epub 2020 Jun 29.
PURPOSE
Uterine-serous-carcinoma (USC) is an aggressive variant of endometrial cancer. On the basis of preliminary results of a multicenter, randomized phase II trial, trastuzumab (T), a humanized-mAb 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.
PATIENTS AND METHODS
Eligible patients had stage III to IV or recurrent disease. Participants were randomized 1:1 to receive C/P for six cycles ± T followed by maintenance T until progression or toxicity. Progression-free survival (PFS) was the primary endpoint; overall survival (OS) and toxicity were secondary endpoints.
RESULTS
Sixty-one 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 months versus 12.9 months in the control and T-arms (HR = 0.46; 90% CI, 0.28-0.76; = 0.005). Median-PFS was 9.3 months versus 17.7 months among 41 patients with stage III to IV disease undergoing primary treatment (HR = 0.44; 90% CI, 0.23-0.83; = 0.015), and 7.0 months versus 9.2 months among 17 patients with recurrent disease (HR = 0.12; 90% CI, 0.03-0.48; = 0.004). OS was higher in the T compared with the control arm, with medians of 29.6 months versus 24.4 months (HR = 0.58; 90% CI, 0.34-0.99; = 0.046). The benefit was most notable in those with stage III to 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; = 0.041). Toxicity was not different between arms.
CONCLUSIONS
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 to IV disease.
目的
子宫浆液性癌（USC）是一种侵袭性子宫内膜癌。基于一项多中心、随机 II 期试验的初步结果，曲妥珠单抗（T），一种针对 Her2/Neu 的人源化单克隆抗体，联合卡铂/紫杉醇（C/P），被认为是治疗晚期/复发性 HER2/Neu 阳性 USC 的一种替代方法。我们报告了 NCT01367002 的更新生存分析。
患者和方法
符合条件的患者患有 III 期至 IV 期或复发性疾病。参与者按 1:1 随机接受 C/P 治疗 6 个周期，然后接受 T 维持治疗，直至进展或出现毒性。无进展生存期（PFS）是主要终点；总生存期（OS）和毒性是次要终点。
结果
61 名患者被随机分配。在中位随访 25.9 个月后，在 58 名可评估患者中，有 43 名出现进展，38 名死亡。更新后的中位 PFS 继续有利于 T 臂，对照组和 T 臂的中位数分别为 8.0 个月和 12.9 个月（HR = 0.46；90%CI，0.28-0.76；= 0.005）。在接受初始治疗的 41 名 III 期至 IV 期疾病患者中，中位 PFS 为 9.3 个月，而 17 名复发性疾病患者为 17.7 个月（HR = 0.44；90%CI，0.23-0.83；= 0.015），而在 17 名复发性疾病患者中，中位 PFS 为 7.0 个月，而 17.7 个月为 9.2 个月（HR = 0.12；90%CI，0.03-0.48；= 0.004）。与对照组相比，T 组的 OS 更高，中位值为 29.6 个月和 24.4 个月（HR = 0.58；90%CI，0.34-0.99；= 0.046）。这种获益在 III 期至 IV 期疾病患者中最为明显，T 臂的中位生存期未达到，而对照组的中位生存期为 24.4 个月（HR = 0.49；90%CI，0.25-0.97；= 0.041）。两组之间的毒性无差异。
结论
在患有晚期/复发性 HER2/Neu 阳性 USC 的女性中，C/P 联合 T 增加了 PFS 和 OS，对 III 期至 IV 期疾病的治疗效果最大。
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