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Background: Recently, numerous combination therapies based on immune checkpoint inhibitors (ICI) and vascular endothelial growth factor (VEGF) inhibitors have been proposed as first-line treatments for advanced renal cell carcinoma (aRCC). Our study aimed to compare the efficacy of these combination regimens by the application of an innovative method that reconstructs individual patient data. Methods: Six phase III studies describing different combination regimens for aRCC were selected. Individual patient data were reconstructed from Kaplan–Meier (KM) curves through the “Shiny method”. Overall survival (OS) and progression-free survival (PFS) were compared among combination treatments and sunitinib. Results were summarized as multi-treatment KM curves. Standard statistical testing was used, including hazard ratio and likelihood ratio tests for heterogeneity. Results: In the overall population of aRCC patients, pembrolizumab + lenvatinib showed the longest median PFS and was expected to determine the longest OS. Pembrolizumab + axitinib, nivolumab + cabozantinib and nivolumab + ipilimumab were similar in terms of PFS, but pembrolizumab + axitinib also demonstrated a better OS. Our subgroup analysis showed that sunitinib is still a valuable option, whereas, in intermediate-poor risk patients, pembrolizumab + axitinib and nivolumab + ipilimumab significantly improve OS compared to sunitinib. Conclusion: The Shiny method allowed us to perform all head-to-head indirect comparisons between these agents in a context in which “real” comparative trials have not been performed.

In the area of evidence-based medicine, the IPDfromKM-Shiny method is an innovative method of survival analysis, midway between artificial intelligence and advanced statistics. Its main characteristic is that an original software investigates the Kaplan-Meier graphs of trials so that individual-patient data are reconstructed. These reconstructed patients represent a new form of original clinical material. The typical objective of investigations based on this method is to analyze the available evidence, especially in oncology, to perform indirect comparisons, and determine the place in therapy of individual agents. This review examined the most recent applications of the IPDfromKM-Shiny method, in which a new web-based software—published in 2021—was used. Reported here are 14 analyses, mostly focused on oncological treatments. Indirect comparisons were based on overall survival or progression free survival. Each of these analyses provided original information to compare treatments with one another and select the most appropriate depending on patient characteristics. These analyses can also be useful to assess equivalence from a regulatory viewpoint. All investigations stressed the importance of heterogeneity to better interpret the evidence generated by IPDfromKM-Shiny investigations. In conclusion, these investigations showed that the reconstruction of individual patient data through this online tool is a promising new method for analyzing trials based on survival endpoints. This new approach deserves further investigation, particularly in the area of indirect comparisons.