Which Factors Help to Determine the Long-Term Response to First-Line Tyrosine Kinase Inhibitors in Patients with Metastatic Renal Cell Carcinoma: A Turkish Multicenter Study

Abstract

In patients with metastatic renal cell carcinoma (mRCC), although immune checkpoint inhibitor (ICI)-tyrosine kinase inhibitor (TKI) combinations or ICI-ICI combinations are typically recommended as first-line treatments, access to these combinations is often limited in developing countries. Therefore, there is a need for predictive markers to identify patients who may achieve long-term responses with single-agent TKIs. Our study aimed to identify such predictive parameters. This multicenter, retrospective study included patients diagnosed with mRCC who received first-line treatment with sunitinib or pazopanib. Patients who did not experience disease progression for 36 months or longer were classified as long-term responders. We investigated the clinical and pathological characteristics predictive of long-term response in these patients. A total of 320 patients from four hospitals were included, with a median age of 60 years (range of 20-89 years). According to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk classification, 109 patients were in the favorable risk group and 211 in the intermediate-poor risk group. The median progression-free survival (PFS) and overall survival (OS) for all patients were 12.5 months and 76.4 months, respectively. In the long-term responders' group, the median PFS was 78.4 months. For the entire group, prior nephrectomy, an Eastern Cooperative Oncology Group (ECOG) performance status (PS) <1, and the absence of brain metastasis were predictive factors for long-term response. In the favorable risk group, the absence of brain metastases predicted long-term response. In the intermediate-poor risk group, prior nephrectomy and an ECOG PS <1 was predictive of long-term response. Thus, in certain individuals with mRCC, TKIs can provide a long-lasting response, which can be predicted by nephrectomy, an ECOG PS <1, and the absence of brain metastases.