Eskander Ramez N, Sill Michael W, Beffa Lindsey, Moore Richard G, Hope Joanie M, Musa Fernanda B, Mannel Robert S, Shahin Mark S, Cantuaria Guilherme H, Girda Eugenia, Lokich Elizabeth, Kavecansky Juraj, Leath Charles A, Gien Lilian T, Hinchcliff Emily M, Lele Shashikant B, Landrum Lisa M, Backes Floor, O'Cearbhaill Roisin E, Baghdadi Tareq Al, Hill Emily K, Thaker Premal H, John Veena S, Welch Stephen, Fader Amanda N, Powell Matthew A, Aghajanian Carol
Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, CA, USA.
Rebecca and John Moores Cancer Center, La Jolla, CA, USA.
Nat Med. 2025 May;31(5):1539-1546. doi: 10.1038/s41591-025-03566-1. Epub 2025 Mar 5.
Historically, the treatment of patients with advanced stage or recurrent endometrial cancer included paclitaxel plus carboplatin. Immunotherapy in combination with chemotherapy resulted in improved clinical outcomes in several solid tumors. In the phase 3 NRG GY018 study, pembrolizumab plus chemotherapy significantly improved investigator-assessed progression-free survival (PFS; primary endpoint) versus placebo plus chemotherapy in patients with advanced/metastatic/recurrent endometrial cancer regardless of mismatch repair status. Here we report on key secondary endpoints and exploratory analyses. Patients were women ≥18 years old with newly diagnosed stage III or IVA endometrial cancer with measurable disease, or stage IVB or recurrent endometrial cancer with or without measurable disease. Patients (n = 810) were randomized (1:1) to pembrolizumab or placebo plus paclitaxel-carboplatin followed by maintenance pembrolizumab or placebo for up to 24 months. Overall survival was a secondary endpoint and PFS per RECIST v.1.1 by blinded independent central review was an exploratory endpoint. Overall survival data were immature; hazard ratios favored pembrolizumab (mismatch repair-proficient: 0.79 (0.53-1.17); 1-sided nominal P = 0.1157; mismatch repair-deficient: 0.55 (0.25-1.19); 1-sided nominal P = 0.0617). Hazard ratios (95% confidence intervals) for PFS per blinded independent central review favored pembrolizumab (mismatch repair-proficient: 0.64 (0.49-0.85); P = 0.0008; mismatch repair-deficient: 0.45 (0.27-0.73); P = 0.0005). These findings further support the use of pembrolizumab plus chemotherapy as first-line treatment for patients with advanced stage or recurrent endometrial cancer regardless of mismatch repair status. ClinicalTrials.gov identifier: NCT03914612 .
从历史上看，晚期或复发性子宫内膜癌患者的治疗方案包括紫杉醇加卡铂。免疫疗法与化疗联合应用在几种实体瘤中取得了更好的临床疗效。在3期NRG GY018研究中，对于晚期/转移性/复发性子宫内膜癌患者，无论错配修复状态如何，帕博利珠单抗联合化疗与安慰剂联合化疗相比，显著改善了研究者评估的无进展生存期（PFS；主要终点）。在此，我们报告关键的次要终点和探索性分析结果。患者为年龄≥18岁的女性，新诊断为III期或IVA期且有可测量病灶的子宫内膜癌，或IVB期或复发性子宫内膜癌，有或无可测量病灶。患者（n = 810）被随机（1:1）分为接受帕博利珠单抗或安慰剂加紫杉醇 - 卡铂治疗，随后接受帕博利珠单抗或安慰剂维持治疗长达24个月。总生存期是次要终点，由盲法独立中央审查根据RECIST v.1.1标准评估的PFS是探索性终点。总生存期数据尚不成熟；风险比倾向于帕博利珠单抗（错配修复 proficient：0.79（0.53 - 1.17）；单侧名义P = 0.1157；错配修复 deficient：0.55（0.25 - 1.19）；单侧名义P = 0.0617）。根据盲法独立中央审查评估的PFS的风险比（95%置信区间）倾向于帕博利珠单抗（错配修复 proficient：0.64（0.49 - 0.85）；P = 0.0008；错配修复 deficient：0.45（0.27 - 0.73）；P = 0.0005）。这些发现进一步支持了无论错配修复状态如何，帕博利珠单抗联合化疗可作为晚期或复发性子宫内膜癌患者的一线治疗方案。ClinicalTrials.gov标识符：NCT03914612 。
