派姆单抗治疗持续性、复发性或转移性宫颈癌可显著延长生存期
2021-09-23   阅读:431   来源:新英格兰医学杂志

意大利米兰比科卡大学Nicoletta Colombo团队研究了派姆单抗治疗持续性、复发性或转移性宫颈癌的效果。2021年9月18日出版的《新英格兰医学杂志》发表了该成果。

派姆单抗对化疗期间进展的程序性死亡配体1(PD-L1)阳性转移性或不可切除的宫颈癌有效。研究人员评估了在有无贝伐单抗的化疗中加入派姆单抗的相对临床获益。

研究组进行了一项双盲、临床3期试验,招募患有持续性、复发性或转移性宫颈癌的患者,将其按1:1随机分组,分别每3周接受派姆单抗(200mg)或安慰剂治疗,最多35个周期,再加上铂基化疗和贝伐单抗(由研究人员自行决定)。双主要终点为无进展生存率和总生存率,分别对PD-L1综合阳性评分为1分或以上的患者、意向治疗人群和PD-L1综合阳性评分为10分或以上的患者进行顺序测试。综合阳性评分定义为PD-L1染色细胞数除以活肿瘤细胞总数,再乘以100。

在548名PD-L1综合阳性评分为1分或以上的患者中,派姆单抗组的中位无进展生存期为10.4个月,显著高于安慰剂组的8.2个月,疾病进展或死亡的危险比为0.62。在意向治疗人群中的617名患者中,无进展生存期分别为10.4个月和8.2个月,危险比为0.65。在317名PD-L1综合阳性评分为10分及以上的患者中,无进展生存期分别为10.4个月和8.1个月,危险比为0.58。

上述三组人群中派姆单抗组和安慰剂组24个月的总生存率分别为53.0%和41.7%(死亡风险比为0.64)、50.4%和40.4%(0.67),以及54.4%和44.6%(0.61),组间差异均显著。最常见的3-5级不良事件是贫血(派姆单抗组为30.3%,安慰剂组为26.9%)和中性粒细胞减少症(分别为12.4%和9.7%)。

研究结果表明,对于同时接受含或不含贝伐单抗化疗的持续性、复发性或转移性宫颈癌患者,采用派姆单抗治疗后的无进展生存期和总生存期明显长于安慰剂。

附:英文原文

Title: Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer | NEJM

Author: Nicoletta Colombo, M.D., Ph.D.,, Coraline Dubot, M.D.,, Domenica Lorusso, M.D., Ph.D.,, M. Valeria Caceres, M.D., Ph.D.,, Kosei Hasegawa, M.D., Ph.D.,, Ronnie Shapira-Frommer, M.D.,, Krishnansu S. Tewari, M.D.,, Pamela Salman, M.D.,, Edwin Hoyos Usta, M.D.,, Eduardo Yaez, M.D.,, Mahmut Gümü, M.D.,, Mivael Olivera Hurtado de Mendoza, M.D.,, Vanessa Samoulian, M.D., Ph.D.,, Vincent Castonguay, M.D.,, Alexander Arkhipov, M.D., Ph.D.,, Sarper Toker, M.D., M.B.A.,, Kan Li, Ph.D.,, Stephen M. Keefe, M.D.,, and Bradley J. Monk, M.D.

Issue&Volume: 2021-09-18

Abstract:

Background

Pembrolizumab has efficacy in programmed death ligand 1 (PD-L1)–positive metastatic or unresectable cervical cancer that has progressed during chemotherapy. We assessed the relative benefit of adding pembrolizumab to chemotherapy with or without bevacizumab.

Methods

In a double-blind, phase 3 trial, we randomly assigned patients with persistent, recurrent, or metastatic cervical cancer in a 1:1 ratio to receive pembrolizumab (200 mg) or placebo every 3 weeks for up to 35 cycles plus platinum-based chemotherapy and, per investigator discretion, bevacizumab. The dual primary end points were progression-free survival and overall survival, each tested sequentially in patients with a PD-L1 combined positive score of 1 or more, in the intention-to-treat population, and in patients with a PD-L1 combined positive score of 10 or more. The combined positive score is defined as the number of PD-L1–staining cells divided by the total number of viable tumor cells, multiplied by 100. All results are from the protocol-specified first interim analysis.

Results

In 548 patients with a PD-L1 combined positive score of 1 or more, median progression-free survival was 10.4 months in the pembrolizumab group and 8.2 months in the placebo group (hazard ratio for disease progression or death, 0.62; 95% confidence interval [CI], 0.50 to 0.77; P<0.001). In 617 patients in the intention-to-treat population, progression-free survival was 10.4 months and 8.2 months, respectively (hazard ratio, 0.65; 95% CI, 0.53 to 0.79; P<0.001). In 317 patients with a PD-L1 combined positive score of 10 or more, progression-free survival was 10.4 months and 8.1 months, respectively (hazard ratio, 0.58; 95% CI, 0.44 to 0.77; P<0.001). Overall survival at 24 months was 53.0% in the pembrolizumab group and 41.7% in the placebo group (hazard ratio for death, 0.64; 95% CI, 0.50 to 0.81; P<0.001), 50.4% and 40.4% (hazard ratio, 0.67; 95% CI, 0.54 to 0.84; P<0.001), and 54.4% and 44.6% (hazard ratio, 0.61; 95% CI, 0.44 to 0.84; P=0.001), respectively. The most common grade 3 to 5 adverse events were anemia (30.3% in the pembrolizumab group and 26.9% in the placebo group) and neutropenia (12.4% and 9.7%, respectively).

Conclusions

Progression-free and overall survival were significantly longer with pembrolizumab than with placebo among patients with persistent, recurrent, or metastatic cervical cancer who were also receiving chemotherapy with or without bevacizumab.

DOI: 10.1056/NEJMoa2112435

 

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