Impact of Clinicopathological Features on Survival in Patients Treated with First-line Immune Checkpoint Inhibitors Plus Tyrosine Kinase Inhibitors for Renal Cell Carcinoma: A Meta-analysis of Randomized Clinical Trials

Context: Immune checkpoint inhibitors (ICIs) have reported unprecedented results in the treatment of metastatic renal cell carcinoma (mRCC) patients, as monotherapy or in combination with other anticancer agents. However, little information is available regarding the association between different clinicopathological features and survival in this setting. Objectives: We performed a meta-analysis aimed at exploring the predictive value of routinely collected clinicopathological data in randomized controlled trials (RCTs) evaluating ICIs plus tyrosine kinase inhibitors (TKI5) in treatment-naive patients with mRCC. Evidence acquisition: We retrieved all the relevant RCTs through PubMed/Medline, Cochrane Library, and EMBASE; additionally, proceedings of the main international oncological meetings were also searched for relevant abstracts. Eligible studies included RCTs assessing first-line ICI-TKI versus sunitinib in treatment-naive mRCC patients; the primary endpoint was overall survival (OS), measured as hazard ratio (HR) with corresponding 95% confidence interval (CI). Evidence synthesis: Overall, three phase III RCTs involving 1769 patients with advanced or metastatic RCC were included. Compared with sunitinib, the ICI-TKI combination significantly decreased the risk of death in patients with Eastern Cooperative Oncology Group performance status (ECOG-PS) 0 (HR, 0.66; 95% CI, 0.57-0.76) and ECOG-PS 1 (HR, 0.64; 95% CI, 0.54-0.77). Similarly, the combination was associated with prolonged OS in patients who were <65 yr old (HR, 0.57; 95% CI, 0.49-0.67), in mRCC patients >= 65 yr old (HR, 0.75; 95% CI, 0.61-0.90), as well as in male (HR, 0.66; 95% CI, 0.56-0.78) and female (HR, 0.66; 95% CI, 0.52-0.83) patients. Conclusions: According to our results, the magnitude of benefit of the ICI-TKI combination over sunitinib monotherapy in treatment-naive mRCC patients was consistent across the clinicopathological subgroups. Despite the limitations affecting the analysis, we believe that the results of the current meta-analysis could assist clinicians and researchers in the design and interpretation of future clinical trials on combination therapies in this setting. Patient summary: First-line combinations of an immune checkpoint inhibitor plus a tyrosine kinase inhibitor improved survival in metastatic renal cell carcinoma (mRCC) patients. This survival benefit was consistent across all subgroups of mRCC patients irrespective of clinicopathological features such as patient performance status, age <65 and >= 65 yr, and male and female gender. (C) 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Automated summary

This study conducted a meta-analysis to explore the predictive value of immune checkpoint inhibitors (ICI) plus tyrosine kinase inhibitors (TKI) in the treatment of metastatic renal cell carcinoma (mRCC) patients. The results showed that the combination therapy had significant survival benefits in different clinicopathological subgroups.