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.
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'.
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.
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.
Therapeutic advances in medical oncology. 2022 Jun 28*** epublish ***
Aly-Khan A Lalani, Daniel Y C Heng, Naveen S Basappa, Lori Wood, Nayyer Iqbal, Deanna McLeod, Denis Soulières, Christian Kollmannsberger
Division of Medical Oncology, Juravinski Cancer Center, McMaster University, 699 Concession Street, Hamilton, ON L8V5C2, Canada., Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada., Cross Cancer Institute, Edmonton, AB, Canada., Queen Elizabeth II Health Sciences Center, Halifax, NS, Canada., Saskatoon Cancer Centre, Saskatoon, SK, Canada., Kaleidoscope Strategic Inc., Toronto, ON, Canada., Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada., Medical Oncology, BC Cancer, Vancouver, BC, Canada.