Immunotherapy combinations in favourable risk score metastatic renal cell carcinoma, an individual patients data metanalysis

INTRODUCTION: Immuno-checkpoint inhibitors (ICIs) represent the backbone for the first line combination therapies of metastatic renal cell carcinoma (mRCC) but their advantage in the IMDC favourable risk compared to sunitinib is debated. To estimate their efficacy we present an individual patient data (IPD) meta-analysis METHODS: A systematic literature search from 2015 to 2024 was conducted on the MEDLINE. Five phase III studies, 1088 patients overall, were analyzed according to PRISMA statement. (JAVELIN RENAL 101, CHECKMATE 214, KEYNOTE 426, CHECKMATE 9ER, CLEAR). An IPD meta-analysis was performed by reconstructing IPD from Kaplan-Meier curves. Primary endpoints were Progression Free Survival (PFS) and overall Survival (OS) in favorable risk patients comparing ICI-based therapies versus sunitinib as well as versus each other. RESULTS: For OS, there was a statistically significant superiority of Pembrolizumab-Lenvatinib rather than Nivolumab-Cabozantinib (HR 0.56 CI 95% 0.34 -0.94), and, even non-statistically significant, vs Pembrolizumab-Axitinib (HR 0.68), vs Avelumab-Axitinib (HR 0.93), and vs Nivolumab + Ipilimumab (HR 0.95). Considering PFS, Pembrolizumab-Lenvatinib showed a significant advantage when compared to Avelumab-Axitinib (HR 0.66 CI 95% 0.46-0.96), to Nivolumab-Cabozantinib (HR 0.61 CI 95% 0.42 -0.90), to Nivolumab-Ipilimumab (HR 0.59 CI 95% 0.42-0.82) and to Pembrolizumab-Axitinib (HR 0.71 CI 95% 0.50 - 0.71). CONCLUSIONS: In IMDC-favorable risk mRCC patients, Pembrolizumab + Lenvatinib showed the best PFS, while none of the arms showed a statistically significant OS advantage versus sunitinib. Further studies would help identify specific patients’ subgroups and establish more personalized treatment decisions.