Chase Dana M, Herrstedt Jørn, Miller Eirwen M, Gilbert Lucy, Zub Oleksandr, Mathews Cara, Angioli Roberto, Teneriello Michael, Gropp-Meier Martina, Powell Matthew A, Reyners Anna K L, Cloven Noelle G, Eminowicz Gemma, Gill Sarah E, Maćkowiak-Matejczyk Beata, Pothuri Bhavana, Samouëlian Vanessa, Jain Angela, Boone Jonathan, Bouberhan Sara, Trinidad Joshua, Braly Patricia, Buttin Barbara, Backes Floor J, Sawyer Brandon, Antony Grace, Garside Jamie, Allonby Odette, McCourt Carolyn K, Mirza Mansoor Raza
David Geffen School of Medicine at the University of California Los Angeles, Department of Obstetrics and Gynecology, Los Angeles, CA, USA.
Zealand University Hospital, Roskilde and University of Copenhagen, Department of Clinical Oncology, Copenhagen, Denmark.
Int J Gynecol Cancer. 2025 May 21;35(8):101935. doi: 10.1016/j.ijgc.2025.101935.
In part 1 of the phase 3 RUBY trial (NCT03981796) in patients with primary advanced or recurrent endometrial cancer, dostarlimab plus carboplatin-paclitaxel significantly improved progression-free and overall survival vs placebo plus carboplatin-paclitaxel. Post hoc analyses examined the impact of adding dostarlimab to chemotherapy, compared with placebo plus chemotherapy, on quality-adjusted time without symptoms of disease progression or toxicity of treatment in this patient population.
Patients were randomized 1:1 to receive dostarlimab/placebo plus chemotherapy every 3 weeks for 6 cycles, followed by dostarlimab/placebo monotherapy every 6 weeks for up to 3 years. Data from the first interim analysis (September 28, 2022) were used, and quality of life (QoL) was assessed with the EuroQoL 5-Dimensions 5-Level questionnaire. Quality-adjusted time without symptoms of disease progression or toxicity of treatment was calculated as the sum product of the restricted mean survival times spent in 3 mutually exclusive states: toxicity, time without symptoms of disease progression or treatment toxicity, and relapse, and utilized each state's corresponding QoL.
In the dostarlimab and placebo arms, 241 and 246 patients were analyzed for safety, respectively. In the overall population, the mean (95% CI) duration of quality-adjusted time without symptoms of disease progression or toxicity of treatment was significantly longer in the dostarlimab arm (24.75 months [22.88 to 26.65 months]) than in the placebo arm (20.34 months [18.95 to 21.76 months]; the mean difference [95% CI] of 4.41 months [2.01 to 6.77 months], p < .001). Benefits in quality-adjusted time without symptoms of disease progression or toxicity of treatment after dostarlimab treatment were observed regardless of mismatch repair/microsatellite instability status or toxicity criteria used and were predominantly driven by the time without symptoms of disease.
Dostarlimab plus carboplatin-paclitaxel treatment is associated with meaningful improvement in survival, avoidance of substantial toxicity, and maintenance of patient-reported QoL in patients with primary advanced or recurrent endometrial cancer.
在3期RUBY试验（NCT03981796）的第1部分中，对于原发性晚期或复发性子宫内膜癌患者，与安慰剂加卡铂-紫杉醇相比，多斯塔利单抗加卡铂-紫杉醇显著改善了无进展生存期和总生存期。事后分析研究了在该患者群体中，与安慰剂加化疗相比，在化疗中添加多斯塔利单抗对无疾病进展症状或治疗毒性的质量调整时间的影响。
患者按1:1随机分组，每3周接受多斯塔利单抗/安慰剂加化疗，共6个周期，随后每6周接受多斯塔利单抗/安慰剂单药治疗，最长3年。使用首次中期分析（2022年9月28日）的数据，采用欧洲五维健康量表问卷评估生活质量（QoL）。无疾病进展症状或治疗毒性的质量调整时间计算为在3个相互排斥状态下花费的受限平均生存时间的乘积之和：毒性、无疾病进展症状或治疗毒性的时间以及复发，并使用每个状态对应的QoL。
在多斯塔利单抗组和安慰剂组中，分别对241例和246例患者进行了安全性分析。在总体人群中，多斯塔利单抗组无疾病进展症状或治疗毒性的质量调整时间的平均（95%CI）持续时间（24.75个月[22.88至26.65个月]）显著长于安慰剂组（20.34个月[18.95至21.76个月]；平均差异[95%CI]为4.41个月[2.01至6.77个月]，p <.001）。无论错配修复/微卫星不稳定性状态或使用的毒性标准如何，多斯塔利单抗治疗后在无疾病进展症状或治疗毒性的质量调整时间方面均有获益，且主要由无疾病症状的时间驱动。
对于原发性晚期或复发性子宫内膜癌患者，多斯塔利单抗加卡铂-紫杉醇治疗可显著改善生存期，避免严重毒性，并维持患者报告的生活质量。
