What is The Comparative Effectiveness of Targeted Therapy versus Immunotherapy in Terms of Overall Survival, Progression-free Survival, and Quality of Life For Patients With Metastatic Renal Cell Carcinoma? : A Systematic Review and Meta-Analysis

Abstract

Introduction: Metastatic renal cell carcinoma (mRCC) poses a significant challenge due to its aggressive nature and poor prognosis. While targeted therapies (e.g., TKIs, mTOR inhibitors) have been standard, immunotherapy, particularly immune checkpoint inhibitors like nivolumab, has emerged as a promising alternative. This systematic review aims to compare the effectiveness of targeted therapy versus immunotherapy in mRCC concerning overall survival (OS), progression-free survival (PFS), and quality of life (QoL).

Methods: This systematic review adhered to PRISMA 2020 guidelines. Eligibility criteria included adult patients with histologically confirmed mRCC, studies comparing targeted therapy and immunotherapy as separate arms, randomized controlled trial design, reporting of OS, PFS, or QoL, minimum 6-month follow-up, and full-text publication. Data extraction covered study design, patient characteristics, intervention details, primary outcomes, QoL outcomes, and adverse events. A comprehensive search was conducted across PubMed, Semantic Scholar, Springer, and Google Scholar using predefined keywords related to Population, Intervention, Comparison, and Outcome (PICO).

Results: Twenty-eight studies were included, predominantly Phase 3 Randomized Controlled Trials. For OS, Nivolumab-based regimens consistently showed significant benefits over Everolimus or Sunitinib (e.g., HR 0.73, p=0.002 for Nivolumab vs. Everolimus). A meta-analysis for OS yielded a combined HR of 0.68 (95% CI: 0.62-0.75, p<0.05), with significant heterogeneity (I2=67%). For PFS, targeted therapies like Lenvatinib plus Everolimus and Cabozantinib consistently showed superiority over Everolimus. Nivolumab showed PFS benefit in some, but not all, studies. A meta-analysis for PFS showed a pooled HR of 0.71 (95% CI: 0.57-0.87, p<0.05), with substantial heterogeneity (I2=96%). Nivolumab consistently improved or maintained QoL compared to Everolimus. Immunotherapy also demonstrated lower rates of severe adverse events and discontinuation compared to targeted therapies.

Discussion: Immunotherapy with nivolumab demonstrated consistent OS and QoL benefits, marking a paradigm shift in mRCC treatment. Targeted therapies excelled in PFS, suggesting their role in rapid disease control. The observed heterogeneity in meta-analyses highlights the diverse patient populations and treatment responses. Limitations include the reliance on indirect comparisons due to a lack of head-to-head trials between newer agents. Personalized treatment strategies considering patient characteristics and molecular markers are crucial.

Conclusion: Both targeted therapies and immunotherapy have revolutionized mRCC treatment. Immunotherapy offers superior overall survival and improved quality of life, while targeted therapies provide effective disease control, particularly in progression-free survival. Future research should focus on direct comparative trials and biomarker identification to further personalize treatment approaches.