Final Results Confirm Effectiveness of Two-Drug Therapy for Advanced Kidney Cancer

Recent comprehensive data from a five-year follow-up of a significant clinical trial demonstrate the sustained benefits of a combined two-drug regimen in treating advanced kidney cancer. The study, published in Nature Medicine, provides valuable insights into long-term outcomes and biomarker correlations, reinforcing the role of pembrolizumab plus axitinib as a first-line treatment option.

The trial, known as KEYNOTE-426, was a Phase 3 study comparing the combination of pembrolizumab, an immune checkpoint inhibitor, with axitinib, a VEGF receptor inhibitor, against sunitinib, a standard therapy. It involved patients with previously untreated advanced clear cell renal cell carcinoma, which is the most prevalent kidney cancer subtype.

Lead investigator Dr. Brian Rini from Vanderbilt University Medical Center stated that this trial was the first to combine a PD-1 inhibitor with an antiangiogenic drug in the first-line setting and boasts the longest follow-up duration among similar studies. The combination works by stimulating the immune system to attack tumor cells and inhibiting the formation of new blood vessels necessary for tumor growth.

Compared to sunitinib, patients receiving pembrolizumab plus axitinib experienced notably longer overall survival (47.2 months vs. 40.8 months) and progression-free survival (15.7 months vs. 11.1 months). Additionally, the objective response rate increased to 60.6% from 39.6%. These results reinforce the improved efficacy of the combination therapy.

Biomarker analyses within the study revealed potential predictors of treatment response. Various RNA signatures, including T-cell-inflamed and angiogenesis profiles, correlated with outcomes such as overall survival and response rates. However, Dr. Rini emphasized the need for further research to validate these biomarkers for personalized treatment selection.

Previous interim analyses, published in the New England Journal of Medicine in 2019, already indicated superior survival and response metrics for the combination therapy. The current extended follow-up solidifies these findings and underlines the importance of immunotherapy and antiangiogenic agents in managing advanced renal cell carcinoma.

This research underscores a significant advancement in renal cancer treatment, illustrating that combining immunotherapy with targeted antiangiogenic therapy offers durable benefits and improved survival prospects for patients. While further studies are needed to refine biomarker-guided therapies, this approach is now a cornerstone of first-line treatment for advanced kidney cancer.