Systemic therapies for metastatic renal cell carcinoma in the second-line setting: A systematic review and network meta-analysis

Abstract

Objectives: To perform a systematic review and network meta-analysis to compare the survival benefit and safety profile of current available second-line treatment options of metastatic renal cell carcinomav. Methods: PubMed, EMBASE, Web of Science, and Cochrane Library were systematically researched for eligible articles which were published before July 20, 2021. Studies comparing overall/progression free survival (OS/PFS), objective response rate (ORR), and/or adverse events (AEs) in patients with metastatic renal cell carcinomav were included. Results: Nine trials (with 4911 patients) were finally included for final network meta-analysis. Cabozantinib, lenvatinib, and lenvatinib plus everolimus were associated with significantly better PFS, OS, and ORR compared with everolimus, and lenvatinib plus everolimus emerged as the best option. As for grade 3 to 4 AEs, nivolumab showed significantly lower risk of AEs compared with everolimus. Other included treatments were associated with significantly increased risk of AEs. When comprehensively assessed the efficacy and safety of included treatments based on the ranking analysis of PFS, ORR, and grade 3 to 4 AEs, lenvatinib plus everolimus, cabozantinib, and nivolumab showed superior efficacy over other treatments, with relatively lower risk of grade 3 to 4 AEs. Conclusions: Among all included therapies, Lenvatinib plus everolimus was identified as the most effective treatment approach, with the best PFS, OS, and ORR. nivolumab was associated with decreased incidence of grade 3 to 4 AEs among included treatment therapies. When comprehensively evaluated the efficacy and safety of included treatment options, lenvatinib plus everolimus, cabozantinb, and nivolumab were associated with better survival benefits and lower risk of AEs. Future studies should focus on the direct comparison of different second-line treatment in real-world populations.

Inhibition of the Mechanistic Targets of Rapamycin Beyond Transplant Immunosuppression: A Mini-Review

“…Temsirolimus and everolimus partially inhibit mTORC1 activation, leading to modest survival benefits in advanced RCC patients, according to the results of the phase III Global ARCC trial. 33,34 As reported from a phase II study, everolimus demonstrated mild antitumor effects in metastatic urinary bladder cancer (UBC) patients resistant to chemotherapy. 35 In another phase II study, only a small portion of patients with advanced UBC responded to everolimus.…”

Linkage between Psychological Factors and Response to Immune Checkpoint Inhibitor Therapy: A Preliminary Study

“…The main ICI drugs include ipilimumab and tremelimumab for CTLA-4 inhibition; nivolumab, pembrolizumab, and cemiplimab for PD-1 inhibition; and atezolizumab, avelumab, and durvalumab for PD-L1 inhibition [1]. Recent meta-analyses 2 of 11 have shown that ICI treatments, especially a combination of these drugs, can have a significant effect on response rate, free survival, and overall survival for various advanced cancer types (e.g., melanoma, non-small-cell carcinoma, renal cell carcinoma) [2,3].…”

The Decision to Surgically Resect Recurrent Renal Cell Carcinoma: More Evidence that Careful Case Selection by Surgeons Is Associated with Better Survival

“…Today’s modern imaging led to tumor size and stage migration, the era of incidentaloma, the acceptance of kidney-sparing operations, and, in parallel, the development of minimally invasive surgery (MIS) and ablative techniques [2] . For patients with stage 4 disease, current systemic therapies, including tyrosine kinase, mTOR, immune checkpoint, and HIF2α inhibitors, have led to a fourfold improvement in overall survival (OS) in comparison to historical controls [3] . However, 30–40% of patients with localized disease eventually experience recurrence and surgeons are asked to play a critical role in their care.…”