Brown University, Providence, Providence, RI, USA.
Fondazione Policlinico Gemelli of Rome, Rome, Italy.
Oncologist. 2022 Dec 9;27(12):1058-1066. doi: 10.1093/oncolo/oyac188.
There is no clear standard of care for advanced/recurrent endometrial cancer (EC) following platinum-based therapy. Dostarlimab is approved for patients with mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) advanced/recurrent EC. This indirect treatment comparison (ITC) assessed dostarlimab efficacy and safety from the single-arm GARNET (NCT02715284) trial compared with doxorubicin from ZoptEC (NCT01767155).
Patient-level data and study variables from GARNET Cohort A1 (dMMR/MSI-H EC) and the ZoptEC doxorubicin control arm were merged. Patients were matched based on eligibility criteria (main analysis population). Safety population included all patients who received treatment. The primary efficacy comparison outcome, overall survival (OS), was calculated using a Cox proportional hazards model, with adjusted stabilized inverse probability of treatment weighting. Modified assessment-scheduled matching Kaplan--Meier analysis was used for progression-free survival (PFS) and time to deterioration (TTD) in quality of life (QoL).
In the main analysis population, median (95% CI) OS was not reached (NR; 18.0 months--NR) for dostarlimab (n = 92) and was 11.2 (10.0-13.1) months for doxorubicin (n = 233; HR: 0.41 [95% CI: 0.28-0.61]); median PFS was 12.2 (3.3-NR) and 4.9 (4.1-6.6) months, respectively. Median TTD in QoL was NR (2.5-NR; n = 61) and 4.5 (4.1-5.4; n = 188) months, respectively. Similar rates of adverse events (AEs, 11.6% vs 15.3%) and serious AEs (34.1% vs 30.1%) were observed with dostarlimab (n = 129) and doxorubicin (n = 249). Grade ≥3 AEs occurred in 48.1% vs 78.3%, respectively.
This ITC suggests a favorable benefit:risk profile for dostarlimab in patients with dMMR/MSI-H advanced/recurrent EC.
铂类治疗后晚期/复发性子宫内膜癌（EC）缺乏明确的护理标准。Dostarlimab 获批用于错配修复缺陷（dMMR）/微卫星高度不稳定（MSI-H）的晚期/复发性 EC 患者。这项间接治疗比较（ITC）评估了 Garnet （NCT02715284）试验中 dostarlimab 相对于 ZoptEC 多柔比星的疗效和安全性（NCT01767155）。
合并了 Garnet Cohort A1 （dMMR/MSI-H EC）和 ZoptEC 多柔比星对照组的患者水平数据和研究变量。根据合格标准（主要分析人群）对患者进行匹配。安全性人群包括所有接受治疗的患者。使用 Cox 比例风险模型计算主要疗效比较结果，即总生存期（OS），并进行调整稳定的逆概率治疗加权。用于无进展生存期（PFS）和生活质量（QoL）恶化时间（TTD）的改良评估预定匹配 Kaplan-Meier 分析。
在主要分析人群中，dostarlimab（n=92）的中位（95%CI）OS 未达到（NR；18.0 个月-NR），多柔比星（n=233）的中位 OS 为 11.2（10.0-13.1）个月（HR：0.41[95%CI：0.28-0.61]）；中位 PFS 分别为 12.2（3.3-NR）和 4.9（4.1-6.6）个月。QoL 的中位 TTD 分别为 NR（2.5-NR；n=61）和 4.5（4.1-5.4；n=188）个月。Dostarlimab（n=129）和多柔比星（n=249）的不良事件（AE）发生率（11.6% vs 15.3%）和严重 AE 发生率（34.1% vs 30.1%）相似。分别有 48.1%和 78.3%的患者发生≥3 级 AE。
这项 ITC 表明，对于 dMMR/MSI-H 晚期/复发性 EC 患者，dostarlimab 具有有利的获益/风险比。
Zotero 插件