The impact of nephrectomy on the clinical outcomes of first-line immunotherapy and tyrosine kinase inhibitors combinations versus sunitinib in advanced renal cell carcinoma: A meta-analysis of randomized studies.

Abstract

e16505 Background: The treatment paradigm for advanced renal cell carcinoma (RCC) has evolved significantly with the introduction of immune checkpoint inhibitors (IO), tyrosine kinase inhibitors (TKIs), and their combination which have shown substantial efficacy, improving survival outcomes over Sunitinib. The role of therapeutic nephrectomy in the era of IO+TKIs remains controversial. Whether the IO+TKI combination offers additional survival advantages over Sunitinib in patients who have or have not undergone therapeutic nephrectomy warrants further investigation. This meta-analysis aims to systematically evaluate and compare the efficacy of IO+TKI combinations versus sunitinib monotherapy in advanced RCC patients, stratified by the presence or absence of therapeutic nephrectomy, to better inform treatment decisions in this evolving clinical landscape. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria included the English language, diagnosis of advanced RCC, randomized studies of IO+TKI versus Sunitinib, and studies that reported overall survival (OS) and progression-free survival (PFS) for advanced RCC with and without nephrectomy. A meta-analysis using the fixed-effects and random-effects models was conducted. Results: Three randomized studies with a total of 1928 patients were included. All studies reported PFS, while only 2 reported OS by nephrectomy status in advanced RCC. The IO+TKI regimens comprised: Avelumab+Axitinib, Nivolumab+Cabozantinib, and Toripalimab plus Axitinib. While there was no OS benefit for IO+TKI when compared to Sunitinib in advanced RCC without nephrectomy (HR = 0.96, 95%CI: 0.71-1.30), IO+TKI maintained a significant PFS advantage over Sunitinib (HR = 0.73, 95%CI: 0.59-0.92). However, IO+TKI combinations had better OS (HR = 0.59, 95%CI: 0.43-0.84) and PFS (HR = 0.57, 95%CI: 0.43-0.75) than Sunitinib in advanced RCC with therapeutic nephrectomy. Conclusions: This meta-analysis highlights the differential impact of therapeutic nephrectomy on the efficacy of first-line IO+TKI combinations compared to Sunitinib in advanced RCC. It suggests that therapeutic nephrectomy may enhance the survival benefits of IO+TKI therapy in advanced RCC. Further prospective studies are warranted to better define the role of nephrectomy in optimizing outcomes for patients receiving modern combination therapies.