Cytoreductive nephrectomy in the era of immune checkpoint inhibitors: a U.S. FDA pooled analysis.

This pooled analysis of patient-level data from trials evaluated the clinical outcomes of patients with metastatic renal cell carcinoma (mRCC) with or without cytoreductive nephrectomy (CN) prior to a combination of immune checkpoint inhibitor (ICI) and anti-angiogenic therapy.

Five trials of ICI plus anti-angiogenic therapy were pooled. Only patients with stage 4 at initial diagnosis were included to ensure that nephrectomy was done for cytoreductive purposes and not to previously treat an earlier stage of disease. Effect of CN prior to ICI on outcomes was evaluated using the Kaplan-Meier method and a Cox proportional hazards regression model, adjusted for age, sex, risk group, performance status, and presence of sarcomatoid differentiation.

A total of 981 patients were included. The estimated median progression-free survival with and without nephrectomy was 15 and 11 months, respectively, and the adjusted hazard ratio (HR) was 0.71 (95% CI: 0.59 to 0.85). The estimated median overall survival with and without nephrectomy was 46 and 28 months, respectively, and the adjusted HR was 0.63 (95% CI: 0.51 to 0.77). Objective response was 60% of patients with vs 46% of patients without CN.

Patients with mRCC with CN prior to ICI plus anti-angiogenic therapy had improved outcomes compared to patients without CN. Selection factors for CN may be prognostic and could not be fully controlled for in this retrospective analysis. Prospective determination of and stratification by prior CN may be considered when designing clinical trials to assess impact of this factor on prognosis.

Journal of the National Cancer Institute. 2024 Mar 14 [Epub ahead of print]

Jaleh Fallah, Haley Gittleman, Chana Weinstock, Elaine Chang, Sundeep Agrawal, Shenghui Tang, Richard Pazdur, Paul G Kluetz, Daniel L Suzman, Laleh Amiri-Kordestani

Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.