美国加州大学圣迭戈分校Ramez N. Eskander团队研究了派姆单抗联合化疗治疗晚期子宫内膜癌对患者预后的影响。相关论文发表在2023年3月27日出版的《新英格兰医学杂志》上。

子宫内膜癌的标准一线化疗是紫杉醇加卡铂。在化疗中加入派姆单抗的益处尚不清楚。

在这项双盲、安慰剂对照、随机、3期临床试验中，研究组将816名患有可衡量疾病（III期或IVA期）、IVB期或复发性子宫内膜癌症的患者按1:1的比例分为两组，一组接受派姆单抗或安慰剂，同时联合紫杉醇加卡铂。派姆单抗或安慰剂的给药计划为每3周一次共6个周期，随后每6周一次最多14个维持周期。

根据患者是否患有错配修复缺陷型（dMMR）或错配修复熟练型（pMMR）疾病，将患者分为两组。如果无治疗间隔至少为12个月，则允许先前的辅助化疗。主要结局是两组患者的无进展生存率。中期分析计划在dMMR队列中至少84例死亡或进展事件和pMMR队列中至少196例事件发生后触发。

在为期12个月的分析中，对dMMR队列中无进展生存率进行Kaplan–Meier估计，派姆单抗组为74%，安慰剂组为38%（进展或死亡的风险比为0.30），相对风险差异为70%。在pMMR队列中，派姆单抗组和安慰剂组的中位无进展生存期分别为13.1个月和8.7个月（风险比为0.54；组间差异显著）。派姆单抗和联合化疗的不良事件与预期一致。

研究结果表明，在晚期或复发性子宫内膜癌患者中，在标准化疗中添加派姆单抗，与单独化疗相比，无进展生存期显著延长。

附：英文原文

Title: Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer | NEJM

Author: Ramez N. Eskander, M.D.,, Michael W. Sill, Ph.D.,, Lindsey Beffa, M.D.,, Richard G. Moore, M.D.,, Joanie M. Hope, M.D.,, Fernanda B. Musa, M.D.,, Robert Mannel, M.D.,, Mark S. Shahin, M.D.,, Guilherme H. Cantuaria, M.D.,, Eugenia Girda, M.D.,, Cara Mathews, M.D.,, Juraj Kavecansky, M.D.,, Charles A. Leath III, M.D., M.S.P.H.,, Lilian T. Gien, M.D.,, Emily M. Hinchcliff, M.D., M.P.H.,, Shashikant B. Lele, M.D.,, Lisa M. Landrum, M.D.,, Floor Backes, M.D.,, Roisin E. O’Cearbhaill, M.D.,, Tareq Al Baghdadi, M.D.,, Emily K. Hill, M.D.,, Premal H. Thaker, M.D.,, Veena S. John, M.D.,, Stephen Welch, M.D.,, Amanda N. Fader, M.D.,, Matthew A. Powell, M.D.,, and Carol Aghajanian, M.D.

Issue&Volume: 2023-03-27

Abstract:

Background

Standard first-line chemotherapy for endometrial cancer is paclitaxel plus carboplatin. The benefit of adding pembrolizumab to chemotherapy remains unclear.

Methods

In this double-blind, placebo-controlled, randomized, phase 3 trial, we assigned 816 patients with measurable disease (stage III or IVA) or stage IVB or recurrent endometrial cancer in a 1:1 ratio to receive pembrolizumab or placebo along with combination therapy with paclitaxel plus carboplatin. The administration of pembrolizumab or placebo was planned in 6 cycles every 3 weeks, followed by up to 14 maintenance cycles every 6 weeks. The patients were stratified into two cohorts according to whether they had mismatch repair–deficient (dMMR) or mismatch repair–proficient (pMMR) disease. Previous adjuvant chemotherapy was permitted if the treatment-free interval was at least 12 months. The primary outcome was progression-free survival in the two cohorts. Interim analyses were scheduled to be triggered after the occurrence of at least 84 events of death or progression in the dMMR cohort and at least 196 events in the pMMR cohort.

Results

In the 12-month analysis, Kaplan–Meier estimates of progression-free survival in the dMMR cohort were 74% in the pembrolizumab group and 38% in the placebo group (hazard ratio for progression or death, 0.30; 95% confidence interval [CI], 0.19 to 0.48; P<0.001), a 70% difference in relative risk. In the pMMR cohort, median progression-free survival was 13.1 months with pembrolizumab and 8.7 months with placebo (hazard ratio, 0.54; 95% CI, 0.41 to 0.71; P<0.001). Adverse events were as expected for pembrolizumab and combination chemotherapy.

Conclusions

In patients with advanced or recurrent endometrial cancer, the addition of pembrolizumab to standard chemotherapy resulted in significantly longer progression-free survival than with chemotherapy alone.

DOI: 10.1056/NEJMoa2302312

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2302312