Is there a preferred first-line therapy for metastatic renal cell carcinoma? A network meta-analysis

Abstract

Background: In recent years, new therapeutic combinations based on immunotherapy provided significant benefits as a first-line treatment for patients with advanced renal cell carcinoma (mRCC). Objective: This work aims to address the lack of head-to-head comparisons and the uncertainty of the benefit from immunotherapy-based combinations in all the International Metastatic RCC Database Consortium (IMDC) subgroups. Design, setting, and participants: A systematic review and a network meta-analysis were performed. Overall survival (OS) in the intention-to-treat (ITT) population was the primary endpoint. OS according to IMDC subgroups (favorable, intermediate, poor), PD-L1 expression, and grade ⩾3 adverse events (AEs) were secondary endpoints. A SUCRA analysis was performed. Results and limitations: Six randomized phase III trials with 5121 patients were included. There was a high likelihood (82%) that nivolumab-cabozantinib was the preferred treatment in OS. The benefit of ICI-based combinations over sunitinib was unclear in the favorable-risk subgroup. Nivolumab-ipilimumab had the best risk/benefit ratio among all the ICI-based combinations. The limitations were the lack of individual patient data; the heterogeneity of patients’ characteristics, trial designs, and follow-up times; and a limited number of studies for indirect comparisons. Conclusions: A customized approach for the first-line treatment of patients with mRCC should consider the risk/benefit profile of each treatment option, especially considering the likeliness of long-term survival finally reached in this setting.

Lenvatinib and Pembrolizumab (Lenvima and Keytruda)

“…The comparators were SUN or standard of care. Three of the ITCs 35,37,38 included outcomes related to efficacy (such as OS and PFS) and safety (TRAEs and treatment discontinuation), and 1 ITC 36 included only studies that reported safety outcomes (TRAEs, treatment discontinuation, and treatment-related mortality).…”

“…36 Two of the published ITCs reported details of the data extraction process either performed or verified in duplicate by 2 independent reviewers. 35,37 Details of the data extraction process were not provided for the other 2 published ITCs. 36,38 In 3 of the 4 published ITCs, the Cochrane risk-of-bias tool was used to assess study quality and, in 1 ITC, study quality was assessed using the Jadad score.…”

“…36,38 In 3 of the 4 published ITCs, the Cochrane risk-of-bias tool was used to assess study quality and, in 1 ITC, study quality was assessed using the Jadad score. 35 Quhal et al (2021b), 36 Cattrini et al� (2021), 37 Nocera et al� (2021)� 38…”

“…Four ITCs that evaluated the efficacy and safety of LEN-PEM in patients with advanced or metastatic RCC were identified in the literature and summarized for this review. [35][36][37][38]…”

“…• The objective of the ITC published by Cattrini et al (2021) 37 was to address the lack of head-to-head comparisons and the uncertainty of the benefit from immunotherapy-based combinations in all of the IMDC subgroups.…”