Summary of Research: Two-Stage Estimation of Overall Survival in the Phase 3 CheckMate 9ER Trial, Adjusting for the Impact of Subsequent Therapy.

IF 4.7 3区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in Therapy Pub Date : 2026-10-08 DOI:10.1007/s12325-026-03773-3

Marc-Oliver Grimm, Emma Karim, Venediktos Kapetanakis, Mickael Lothgren, Alessia Ogareva, Pragya Shukla, James Truscott, Camillo Porta

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Abstract

This is a summary of a post hoc analysis of the phase 3 CheckMate 9ER study. CheckMate 9ER demonstrated a significant overall survival (OS) benefit for first-line cabozantinib plus nivolumab (CaboNivo) versus sunitinib (SUN) in patients with advanced renal cell carcinoma (aRCC). However, receiving subsequent therapy can distort true OS benefits. This analysis used two-stage estimation (TSE) to model a hypothetical scenario to assess the OS benefit of CaboNivo versus SUN, removing the effect of subsequent treatment. In stage 1, multivariate modeling estimated the extent to which subsequent therapy extended OS in patients who discontinued their original study treatment. In stage 2, an adjusted hazard ratio (HR) for OS assessed the relative impact of CaboNivo versus SUN without the effects of subsequent treatment. TSE-adjusted counterfactual median OS [95% confidence interval (CI)] was 42.7 (38.4-49.1) months for CaboNivo and 21.3 (18.1-24.9) months for SUN [HR 0.53 (95% CI 0.43-0.65; p < 0.001)]; unadjusted estimates were 46.5 (40.6-53.7) months for CaboNivo and 35.5 (29.2-42.8) months for SUN [HR 0.79 (95% CI 0.65-0.96; p = 0.0196)]. Removing the effect of subsequent therapy increased the estimated OS benefit of CaboNivo versus SUN, reinforcing CaboNivo as a first-line standard of care for aRCC.Trial Registration NCT03141177.

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研究总结：3期CheckMate 9ER试验中总生存期的两阶段估计，调整后续治疗的影响。

这是对CheckMate 9ER 3期研究的事后分析总结。CheckMate 9ER显示，在晚期肾细胞癌（aRCC）患者中，一线卡博赞替尼加尼伏单抗（CaboNivo）与舒尼替尼（SUN）相比，总生存期（OS）显著改善。然而，接受后续治疗可能会扭曲真正的OS益处。该分析使用两阶段估计（TSE）来模拟一个假设的场景，以评估CaboNivo与SUN的OS获益，排除后续治疗的影响。在第1阶段，多变量建模估计了停止原始研究治疗的患者后续治疗延长OS的程度。在第二阶段，调整后的OS风险比（HR）评估了CaboNivo与SUN在没有后续治疗影响的情况下的相对影响。经上证指数调整后的反事实中位OS[95%可信区间（CI）]为CaboNivo 42.7（38.4-49.1）个月，SUN 21.3（18.1-24.9）个月[HR 0.53 (95% CI 0.43-0.65; p

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来源期刊

Advances in Therapy 医学-药学

CiteScore

7.20

自引率

2.60%

发文量

353

审稿时长

6-12 weeks

期刊介绍： Advances in Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Advances in Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.