Powell Matthew A, Cibula David, O'Malley David M, Boere Ingrid, Shahin Mark S, Savarese Antonella, Chase Dana M, Gilbert Lucy, Black Destin, Herrstedt Jørn, Sharma Sudarshan, Kommoss Stefan, Gold Michael A, Thijs Anna M, Ring Kari, Bolling Magnus Frödin, Buscema Joseph, Gill Sarah E, Nowicki Paul, Nevadunsky Nicole, Callahan Michael, Willmott Lyndsay, McCourt Carolyn, Billingsley Caroline, Ghamande Sharad A, He Zangdong, Balas Morad Marco, Stevens Shadi, Fleming Evelyn, Mirza Mansoor Raza
National Cancer Institute-sponsored NRG Oncology, Washington University School of Medicine, St Louis, MO, USA.
Department of Gynaecology, Obstetrics and Neonatology, General University Hospital in Prague, First Faculty of Medicine, Charles University, Prague, Czech Republic.
Gynecol Oncol. 2025 Jan;192:40-49. doi: 10.1016/j.ygyno.2024.10.022. Epub 2024 Nov 12.
Part 1 of the RUBY trial (NCT03981796) demonstrated improved survival in patients with primary advanced or recurrent endometrial cancer (EC) treated with dostarlimab plus carboplatin-paclitaxel versus placebo plus carboplatin-paclitaxel. Here, we examine additional efficacy and safety data from patients with mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) EC in the RUBY trial.
Patients were randomized 1:1 to dostarlimab 500 mg or placebo plus carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab or placebo every 6 weeks for up to 3 years. In the dMMR/MSI-H population of RUBY Part 1, analysis of progression-free survival by investigator assessment compared with blinded independent central review, sensitivity analyses of the source-verified population compared with the randomized population, and analysis of safety in this population were completed.
In total, 118 patients with dMMR/MSI-H were enrolled in the RUBY trial (53, dostarlimab arm; 65, placebo arm). At the first interim analysis, a 72% reduction in the risk of progression or death (P < 0.0001) was seen with dostarlimab plus carboplatin-paclitaxel by investigator assessment per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), which was consistent with blinded independent central review per RECIST v1.1. Likewise, sensitivity analyses of the source-verified dMMR/MSI-H population compared with the randomized dMMR/MSI-H population were consistent for progression-free survival and overall survival. Safety results seen in the dMMR/MSI-H population were similar to those previously reported for the overall population.
All primary and secondary efficacy assessments demonstrate the consistent benefit of dostarlimab plus carboplatin-paclitaxel. The improvements seen in survival and the manageable safety profile support the favorable benefit-risk profile for dostarlimab plus carboplatin-paclitaxel in patients with dMMR/MSI-H primary advanced or recurrent EC.
RUBY试验（NCT03981796）的第1部分表明，与安慰剂加卡铂-紫杉醇相比，接受多斯塔利单抗加卡铂-紫杉醇治疗的原发性晚期或复发性子宫内膜癌（EC）患者的生存率有所提高。在此，我们研究了RUBY试验中错配修复缺陷/微卫星高度不稳定（dMMR/MSI-H）EC患者的其他疗效和安全性数据。
患者按1:1随机分组，每3周接受一次500 mg多斯塔利单抗或安慰剂加卡铂-紫杉醇治疗，共6个周期，随后每6周接受一次多斯塔利单抗或安慰剂治疗，最长持续3年。在RUBY第1部分的dMMR/MSI-H人群中，完成了研究者评估的无进展生存期分析与盲法独立中心审查的比较、源验证人群与随机人群的敏感性分析以及该人群的安全性分析。
总共有118例dMMR/MSI-H患者纳入了RUBY试验（多斯塔利单抗组53例；安慰剂组65例）。在首次中期分析中，根据实体瘤疗效评价标准第1.1版（RECIST v1.1），研究者评估显示多斯塔利单抗加卡铂-紫杉醇使疾病进展或死亡风险降低了72%（P<0.0001），这与根据RECIST v1.1进行的盲法独立中心审查结果一致。同样，源验证的dMMR/MSI-H人群与随机的dMMR/MSI-H人群的敏感性分析在无进展生存期和总生存期方面也是一致的。dMMR/MSI-H人群的安全性结果与之前报道的总体人群结果相似。
所有主要和次要疗效评估均显示多斯塔利单抗加卡铂-紫杉醇具有一致的益处。生存率的提高和可控的安全性表明，多斯塔利单抗加卡铂-紫杉醇对于dMMR/MSI-H原发性晚期或复发性EC患者具有良好的效益风险比。
