Comparing efficacy and safety of first-line treatment of metastatic renal cell carcinoma: A Bayesian network meta-regression analysis

Abstract

BackgroundThis Bayesian network meta-regression analysis provides a head-to-head comparison of first-line therapeutic immune checkpoint inhibitors (ICI) and tyrosine kinase inhibitors (TKI) combinations for metastatic renal cell carcinoma (mRCC) using median follow-up time as covariate.MethodsWe searched Six databases for a comprehensive analysis of randomised clinical trials (RCTs). Comparing progression free survival (PFS) and overall survival (OS) of different interventions at the same time node by Bayesian network meta-analysis. Bayesian network meta-regression analysis was performed on objective response rate (ORR), adverse events (AEs) (grade ≥ 3) and the hazard ratios (HR) associated with PFS and OS, with the median follow-up time as the covariate.ResultsEventually a total of 22 RCTs reporting 11,090 patients with 19 interventions. Lenvatinib plus Pembrolizumab (LenPem) shows dominance of PFS, and Pembrolizumab plus Axitinib (PemAxi) shows superiority in OS at each time point. After meta-regression analysis, for HRs of PFS, LenPem shows advantages; for HRs of OS, PemAxi shows superiority; For ORR, LenPem provides better results. For AEs (grade ≥ 3), Atezolizumab plus Bevacizumab (AtezoBev) is better.ConclusionConsidering the lower toxicity and the higher quality of life, PemAxi should be recommended as the optimal therapy in treating mRCC.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD4202236775.

Banana-shaped survival curves of metastatic renal cell carcinoma treated with first-line immune-combinations, not just a matter of “palateau”

“…In the last years, the first-line treatment of metastatic renal cell carcinoma (mRCC) has deeply changed with the approval of immune checkpoint inhibitors (ICIs) in combination with or without tyrosine kinase inhibitors (TKIs). 1 , 2 …”

“…The first-line combinations have shown an advantage in terms of overall survival (OS) (range HR: 0.70–0.84), progression-free survival (PFS) (range HR: 0.47–0.86) and overall response rate (ORR) (range: 39.3–71.3% vs 28–40%) 1 , 3 compared with sunitinib.…”

“… 3 The two types of immuno-combinations differentiate, other than the toxicity profile, for the derived clinical outcomes in terms of ORR and PFS that generally favor the ICI-TKI combination. 1 , 4 , 5 However, the survival updates reported at ASCO 2023 have raised many questions on the long-term survival benefit of the main first-line immuno-combinations approved in Europe. 6–8 These mainly arise from the different shapes of the Kaplan–Meier survival curves (e.g.…”