Navigating second-line therapy in metastatic renal cell carcinoma: a comparative analysis of immune checkpoint inhibitors and tyrosine kinase inhibitors: a study of Turkish Oncology Group Kidney Cancer Consortium.

Background: Despite progress in treatment, many metastatic renal cell carcinoma (mRCC) patients still experience progression after first-line tyrosine kinase inhibitor (TKI), necessitating effective second-line options. While guidelines endorse combination therapies, accessibility limitations often restrict therapy to TKI monotherapy.

Objectives: Existing decision-making relies on limited evidence, lacking direct comparisons between the leading second-line options (cabozantinib and nivolumab) which surpass everolimus in advanced mRCC. To address this gap, this study compares the efficacy of TKI versus nivolumab in second line while investigating factors influencing outcomes.

Design: This was a retrospective cohort study.

Methods: Turkish Oncology Group Kidney Cancer Consortium includes more than 1000 mRCC patients from 13 centers in Türkiye. It has the largest national data. We extracted 214 patients treated with a TKI in the first line and nivolumab or TKI in the second line.

Results: The median overall survival (OS) and time to treatment failure (TTF) were similar in the TKI-TKI and TKI-immune checkpoint inhibitor (ICI; 41.1 and 44.8 months, p = 0.446 for OS; 27.4 and 29.8 months, p = 0.857 for TTF). The presence of previous nephrectomy for TTF made a significant difference in univariable and multivariable analysis. Bone metastases negatively affected TTF in both univariable and multivariable analyses. In the neutrophil-to-lymphocyte ratio (NLR)-high group, OS and TTF were longer in patients treated with TKI-ICI than in the TKI-TKI. In multivariable analysis, NLR was an independent prognostic factor for OS and TTF to select ICI in the second-line.

Conclusion: Our analysis revealed no significant difference in OS between patients receiving ICIs or TKIs as second-line therapy. In the subgroup of patients with elevated NLR, ICI therapy was found to cause no improvement in OS. This finding suggests the potential utility of NLR as a biomarker to guide targeted selection of ICI therapy among patients progressing after first-line TKIs. Furthermore, our study identified other noteworthy prognostic factors influencing outcomes, including the presence of bone or liver metastases, Eastern Cooperative Oncology Group performance status, and International Metastatic Renal Cell Carcinoma Database Consortium risk score.