Tyrosine kinase inhibitors and immunotherapy combinations in renal cell carcinoma

Area of Science:

• Oncology
• Immunotherapy
• Pharmacology

Background:

• Metastatic renal cell carcinoma (mRCC) treatment has evolved with antiangiogenics like tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs).
• These therapies have significantly improved patient outcomes and altered the disease's natural history.
• Current research focuses on combining ICIs with VEGFR-directed TKIs.

Purpose of the Study:

• To review clinical data for single-agent TKIs and ICIs in mRCC.
• To discuss the rationale for combining ICIs and TKIs based on preclinical and clinical evidence.
• To explore challenges in selecting treatment regimens and developing predictive biomarkers for mRCC.

Main Methods:

• Review of clinical trial data for axitinib plus pembrolizumab (KEYNOTE-426) and axitinib plus avelumab (JAVELIN RENAL 101).
• Analysis of preclinical and clinical evidence supporting combination therapy.
• Discussion of current challenges in mRCC treatment selection and biomarker development.

Main Results:

• Combination regimens like axitinib plus pembrolizumab and axitinib plus avelumab show improved outcomes compared to sunitinib in treatment-naïve mRCC patients.
• Single-agent TKIs and ICIs have demonstrated efficacy in mRCC.
• Rationale for combining ICIs and TKIs is supported by emerging evidence.

Conclusions:

• Combination therapy with ICIs and VEGFR-directed TKIs represents a significant advancement in mRCC treatment.
• Further research is needed to address challenges in regimen selection and identify predictive biomarkers.
• Optimizing treatment strategies is crucial for improving long-term outcomes in mRCC patients.