Balancing the Risk-Benefit Ratio of Immune Checkpoint Inhibitor and Anti-VEGF Combination Therapy in Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

Abstract

BackgroundAlthough immune checkpoint inhibitors (ICIs) combined with vascular endothelial growth factor receptor (VEGFR)-targeted therapy and sunitinib monotherapy have been widely applied to metastatic renal cell carcinoma (mRCC), effectiveness and safety data are still lacking. To optimize clinical decision-making, we conducted a systematic review and meta-analysis of published randomized clinical trials to characterize the efficacy and the risk of adverse events (AEs) in patients treated with ICIs plus anti-VEGF therapy.Materials and MethodsWe used PubMed, EMBASE, and the Cochrane Library to retrieve randomized controlled trials (RCTs) published before March 27, 2021. The efficacy outcomes were progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). The pooled risk ratio (RR) and 95% confidence intervals (CI) of AEs were calculated in the safety analysis.ResultsSix RCTs involving 4,227 patients were identified after a systematic search. For OS, ICI and anti-VEGF combination therapy decreased mortality approximately 30% in the intention-to-treat population (ITT) (hazard ratio (HR) = 0.70, 95% CI: 0.57–0.87), but there was no statistical difference in patients evaluated as “favorable” by the International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) criteria compared with monotherapy (HR = 0.90, 95% CI: 0.55–1.46, p = 0.66). In terms of PFS, the progression risk for all participants declined 35% (HR = 0.65, 95% CI: 0.50–0.83) and patients evaluated as “poor” by IMDC benefited further (HR = 0.46, 95% CI: 0.36–0.58). No evident divergence was found in age and sex subgroups. The RRs of all-grade hypertension, arthralgia, rash, proteinuria, high-grade (grades 3–5) arthralgia, and proteinuria developed after combination therapy were increased compared with sunitinib. The risk of high-grade hypertension and rash showed no statistical difference. However, the risk of hand-foot skin reaction (HFSR), stomatitis, and dysgeusia decreased in combination therapy groups.ConclusionsCompared with sunitinib, OS, PFS, and ORR were significantly improved in patients receiving ICI and anti-VEGF combination therapy at the expense of increased specific AEs. More attention should be paid to individualized application of these combination therapies to achieve the best benefit-risk ratio in the clinic.Systematic Review Registration[https://inplasy.com/] INPLASY: 202130104.

Comprehensive analysis of 7-methylguanosine and immune microenvironment characteristics in clear cell renal cell carcinomas

“…About 400,000 people worldwide suffer from renal cell carcinoma every year, accounting for about 2%–3% of all cancers ( Siegel et al, 2021 ; Sung et al, 2021 ). With the development of endoscopy and the improvement of adjuvant chemotherapy and immunotherapy, the mortality rate has decreased in developed areas ( Antonelli et al, 2018 ; Tao et al, 2021 ). The successful application of immunotherapy in many kinds of cancer and further study of the tumor immune microenvironment may change our current management mode of patients and help some patients achieve long-term survival and even achieve the goal of clinical cure ( Gandara et al, 2018 ; Mazieres et al, 2021 ).…”

Tat-hspb1 Suppresses Clear Cell Renal Cell Carcinoma (ccRCC) Growth via Lysosomal Membrane Permeabilization

“…Combination therapy does improve the prognosis in patients with RCC, but long-term exposure to ICIs can cause resistance owing to mechanisms including neoantigen loss, defects in antigen presentation, alternative immune checkpoints, etc. Furthermore, the incidence of adverse events such as proteinuria and rash increased compared with monotherapy [ 7 ]. Furthermore, the limited number of targeted pathways in ccRCC therapy leaves non-responding patients with few therapeutic options.…”