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乐伐替尼联合派姆单抗治疗晚期子宫内膜癌可显著延长生存期
作者:小柯机器人 发布时间:2022/1/23 17:09:42

美国纽约纪念斯隆·凯特林癌症中心Vicky Makker团队研究了乐伐替尼联合派姆单抗治疗晚期子宫内膜癌的疗效。2022年1月19日出版的《新英格兰医学杂志》发表了这项成果。

铂类化疗失败后晚期子宫内膜癌的标准治疗尚不清楚。

在临床3期试验中,研究组招募晚期子宫内膜癌患者,此前至少接受过一种铂类化疗方案,将其按1:1的比例随机分配,分别接受乐伐替尼+派姆单抗治疗,或治疗医师选择的化疗。

两个主要终点是根据实体瘤疗效评价标准1.1版在盲法独立中心评价中评估的无进展生存期和总生存期。对错配修复完整(pMMR)疾病患者和所有患者的终点进行评估。对安全性也进行了评估。

研究组共招募了827名患者(697名患有pMMR疾病,130名患有错配修复缺陷疾病),随机分组后,411名接受乐伐替尼联合派姆单抗治疗,416名接受化疗。乐伐替尼+派姆单抗组的pMMR人群的中位无进展生存期为6.6个月,显著长于化疗组的3.8个月,进展或死亡的危险比为0.60;乐伐替尼+派姆单抗组的总体中位无进展生存期为7.2个月,亦显著长于化疗组的3.8个月,危险比为0.56。

乐伐替尼+派姆单抗组的pMMR人群的中位总生存期为17.4个月,显著长于化疗组的12.0个月,死亡危险比为0.68;乐伐替尼+派姆单抗组的总体中位总生存期为18.3个月,亦显著长于化疗组的11.4个月,危险比为0.62。乐伐替尼+派姆单抗组中88.9%的患者发生3级及以上不良事件,化疗组有72.7%。

研究结果表明,在晚期子宫内膜癌患者中,与化疗相比,乐伐替尼联合派姆单抗治疗可显著延长无进展生存期和总生存期。

附:英文原文

Title: Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer

Author: Vicky Makker, M.D.,, Nicoletta Colombo, M.D.,, Antonio Casado Herráez, M.D.,, Alessandro D. Santin, M.D.,, Emeline Colomba, M.D.,, David S. Miller, M.D.,, Keiichi Fujiwara, M.D.,, Sandro Pignata, M.D.,, Sally Baron-Hay, M.B., B.S.,, Isabelle Ray-Coquard, M.D.,, Ronnie Shapira-Frommer, M.D.,, Kimio Ushijima, M.D.,, Jun Sakata, M.D.,, Kan Yonemori, M.D.,, Yong Man Kim, M.D.,, Eva M. Guerra, M.D.,, Ulus A. Sanli, M.D.,, Mary M. McCormack, F.R.C.R.,, Alan D. Smith, M.D.,, Stephen Keefe, M.D.,, Steven Bird, M.S.,, Lea Dutta, Pharm.D.,, Robert J. Orlowski, M.D.,, and Domenica Lorusso, M.D.

Issue&Volume: 2022-01-19

Abstract:

Background

Standard therapy for advanced endometrial cancer after failure of platinum-based chemotherapy remains unclear.

Methods

In this phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with advanced endometrial cancer who had previously received at least one platinum-based chemotherapy regimen to receive either lenvatinib (20 mg, administered orally once daily) plus pembrolizumab (200 mg, administered intravenously every 3 weeks) or chemotherapy of the treating physician’s choice (doxorubicin at 60 mg per square meter of body-surface area, administered intravenously every 3 weeks, or paclitaxel at 80 mg per square meter, administered intravenously weekly [with a cycle of 3 weeks on and 1 week off]). The two primary end points were progression-free survival as assessed on blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1, and overall survival. The end points were evaluated in patients with mismatch repair–proficient (pMMR) disease and in all patients. Safety was also assessed.

Results

A total of 827 patients (697 with pMMR disease and 130 with mismatch repair–deficient disease) were randomly assigned to receive lenvatinib plus pembrolizumab (411 patients) or chemotherapy (416 patients). The median progression-free survival was longer with lenvatinib plus pembrolizumab than with chemotherapy (pMMR population: 6.6 vs. 3.8 months; hazard ratio for progression or death, 0.60; 95% confidence interval [CI], 0.50 to 0.72; P<0.001; overall: 7.2 vs. 3.8 months; hazard ratio, 0.56; 95% CI, 0.47 to 0.66; P<0.001). The median overall survival was longer with lenvatinib plus pembrolizumab than with chemotherapy (pMMR population: 17.4 vs. 12.0 months; hazard ratio for death, 0.68; 95% CI, 0.56 to 0.84; P<0.001; overall: 18.3 vs. 11.4 months; hazard ratio, 0.62; 95% CI, 0.51 to 0.75; P<0.001). Adverse events of grade 3 or higher occurred in 88.9% of the patients who received lenvatinib plus pembrolizumab and in 72.7% of those who received chemotherapy.

Conclusions

Lenvatinib plus pembrolizumab led to significantly longer progression-free survival and overall survival than chemotherapy among patients with advanced endometrial cancer.

DOI: 10.1056/NEJMoa2108330

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2108330

 

期刊信息

The New England Journal of Medicine:《新英格兰医学杂志》,创刊于1812年。隶属于美国麻省医学协会,最新IF:70.67
官方网址:http://www.nejm.org/
投稿链接:http://www.nejm.org/page/author-center/home