Comparison of TKI and CPI strategies as first-line treatment of patients with advanced renal cell carcinoma: Real-world outcome data from the German research platform CARAT.
Authors: Goebell Peter J. , Boegemann Martin , Nusch Arnd , Grünwald Viktor , Mueller Lothar , von der Heyde Eyck , Reichert Dietmar , Martens Uwe Marc , Lennartz Carolin , Koska Michaela , Jänicke Martina , Potthoff Karin , Marschner Norbert , Grüllich Carsten , Staehler Michael D. 
Published: June 2024

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Background: Immune checkpoint inhibitors (CPI), in combination with tyrosine kinase inhibitors (TKI) or with another CPI, expanded the therapeutic options for advanced or metastatic renal cell carcinoma (mRCC) beyond TKI-Monotherapy. However, no head-to-head clinical trials comparing 1st-line (1L) CPI+CPI vs. TKI+CPI have been performed. Here, we analyzed outcome of non-randomized patients (pts) treated 1L with one of the three strategies in routine care. Methods: CARAT (NCT03374267) is an ongoing, prospective, observational, longitudinal, multicenter clinical registry for mRCC pts in Germany. Details on (sequential) treatments, patient and tumor characteristics and clinical and patient-reported outcomes are collected. Follow-up is until death or up to 3 years. By January 2024, almost 1100 pts had been enrolled by 148 sites. Pts with start of 1L treatment after 15/01/2019 were analyzed (data cut 06/30/2023). PFS and OS were estimated using the Kaplan-Meier method. Inverse probability of treatment weighting (IPTW) by propensity score analysis was used to compare PFS (primary endpoint) and OS (secondary endpoint) between 1L TKI or CPI+CPI or TKI+CPI. IPTW was performed for the following variables: age, sex, IMDC risk groups, histology, any comorbidity, Charlson comorbidity index, metastatic stage, type of metastasis and number of metastatic sites. After IPTW, the three treatment groups were comparable for the variables listed above. Results: From 2019 until data cut for this analysis, 991 pts were investigated, thereof 418 pts (42%) received TKI+CPI, 242 pts (24%) CPI+CPI and 263 pts (27%) received TKI monotherapy as 1L. 51/61/80% of pts had a progression or death after 1L (TKI+CPI/CPI+CPI/TKI strategy group). IPTW-adjusted median PFS was 12.7 months (95% confidence interval (CI) [10.4 – 15.6]) for TKI+CPI, 8.0 [6.3 – 10.9] months for CPI+CPI and 9.7 [7.4 – 12.0] months for TKI. Hazard ratio (HR) was 1.24 (0.97 – 1.58) for CPI+CPI versus TKI+CPI and 1.33 (1.09 – 1.61) for TKI versus TKI+CPI. 30/42/51% of pts had died (TKI+CPI/CPI+CPI/TKI strategy group). IPTW-adjusted median OS was 31.5 [26.4 – NA] months for TKI+CPI, 22.3 [17.1 – 37.5] months for CPI+CPI and 31.4 [22.8 – 37.1] months for TKI. HR was 1.30 (0.98 – 1.73) for CPI+CPI versus TKI+CPI and 1.08 (0.83 – 1.41) for TKI versus TKI+CPI. Subgroup analyses by IMDC score as well as data on quality of life and on subsequent line treatments will also be presented. Conclusions: IPWT-adjusted outcome analysis of real-world data in the CARAT registry did not detect significant differences in PFS and OS between pts treated with 1L TKI+CPI compared to CPI+CPI when adjusted for a wide range of potential confounding variables. Further analyses in other cohorts are warranted to confirm these findings.