Evolving landscape of first-line combination therapy in advanced renal cancer: a systematic review
Aly-Khan A Lalani1, Daniel Y C Heng2, Naveen S Basappa3
1Division of Medical Oncology, Juravinski Cancer Center, McMaster University, 699 Concession Street, Hamilton, ON L8V5C2, Canada.
Background:
Renal cell carcinoma (RCC) is a common malignancy with approximately 30% of cases diagnosed at the advanced or metastatic stage. While single-agent vascular endothelial growth factor-targeted therapy has been a mainstay of treatment, data from multiple phase III trials assessing first-line immune checkpoint inhibitor (ICI) combinations have demonstrated a significant survival benefit.
Methods:
A systematic search of the published and presented literature was performed to identify phase III trials assessing ICI combination regimens in RCC using search terms 'immune checkpoint inhibitors' AND 'renal cell carcinoma,' AND 'advanced'.
Results:
Six phase III trials showed significant benefits for ICI combinations compared with sunitinib. Nivolumab plus ipilimumab significantly improved overall survival [OS; median, 47.0 versus 26.6 months, hazard ratio (HR) = 0.68, 95% confidence interval (CI) = 0.58-0.81, p < 0.0001) and progression-free survival (PFS; median 11.6 versus 8.3 months, HR = 0.73, 95% CI = 0.61-0.87, p = 0.0004) in International Metastatic renal cell carcinoma Database Consortium intermediate and poor-risk patients. OS was also significantly improved for ICI plus tyrosine kinase inhibitor combinations regardless of risk, including pembrolizumab plus either axitinib (HR = 0.73, 95% CI = 0.60-0.88, p < 0.001) or lenvatinib (HR = 0.66, 95% CI = 0.49-0.88, p = 0.005) and nivolumab plus cabozantinib (HR = 0.66, 95% CI = 0.50-0.87, p = 0.003). No new safety signals were identified.
Conclusions:
Phase III first-line trials of ICI combinations showed survival benefits compared with a control arm of sunitinib. Global access to these combinations should be made available to patients with advanced RCC.
Insights
First-line immune checkpoint inhibitor (ICI) combinations significantly improve survival in advanced renal cell carcinoma (RCC) compared to sunitinib. These effective ICI regimens should be accessible to all patients with advanced RCC.
Area of Science:
- Oncology
- Immunotherapy
- Clinical Trials
Background:
- Renal cell carcinoma (RCC) frequently presents at advanced or metastatic stages, with approximately 30% of cases diagnosed late.
- Vascular endothelial growth factor-targeted therapy has been the standard first-line treatment for advanced RCC.
- Emerging data from phase III trials indicate superior survival outcomes with first-line immune checkpoint inhibitor (ICI) combinations.
Purpose of the Study:
- To systematically review phase III trials evaluating the efficacy of first-line immune checkpoint inhibitor (ICI) combination regimens in advanced renal cell carcinoma (RCC).
- To compare the survival benefits of ICI combinations against standard treatments like sunitinib.
- To assess the safety profile of these novel combination therapies.
Main Methods:
- A systematic literature search was conducted for phase III trials involving ICI combinations in advanced RCC.
- Search terms included 'immune checkpoint inhibitors,' 'renal cell carcinoma,' and 'advanced.'
- Data from identified trials were analyzed to compare overall survival (OS) and progression-free survival (PFS).
Main Results:
- Six phase III trials demonstrated significant survival benefits for ICI combinations over sunitinib in advanced RCC.
- Nivolumab plus ipilimumab showed significant improvements in OS and PFS for intermediate and poor-risk patients.
- ICI plus tyrosine kinase inhibitor combinations, including pembrolizumab with axitinib or lenvatinib, and nivolumab with cabozantinib, also significantly improved OS across risk groups.
- No new safety concerns were identified with these ICI combinations.
Conclusions:
- First-line ICI combinations offer significant survival advantages for patients with advanced renal cell carcinoma compared to sunitinib.
- These promising treatment options should be made globally accessible to eligible patients.
- ICI combinations represent a new standard of care in the first-line treatment of advanced RCC.
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