Trial Watch: combination of tyrosine kinase inhibitors (TKIs) and immunotherapy

Area of Science:

• Oncology
• Immunology
• Pharmacology

Background:

• Targeted therapies, including tyrosine kinase inhibitors (TKIs), have been crucial in cancer treatment by inhibiting pro-tumorigenic signals.
• TKIs have diverse mechanisms, targeting cancer cells, normalizing angiogenesis, or affecting hematologic cells, with emerging roles in modulating immune responses.
• The interplay between TKIs and the immune system provides a rationale for combining TKIs with immunotherapy, enhancing cancer immunosurveillance.

Purpose of the Study:

• To summarize active clinical trials investigating the combination of TKIs with various immunotherapeutic strategies for cancer patients.
• To highlight the potential synergistic effects observed in preclinical and clinical settings.
• To underscore the need for optimizing drug combinations, dosing, and scheduling for enhanced cancer care.

Main Methods:

• Review and summary of ongoing clinical trials.
• Analysis of preclinical and clinical data on TKI-immunotherapy combinations.
• Identification of approved TKI-immunotherapy combinations by regulatory bodies like the FDA.

Main Results:

• Combinations of TKIs and immunotherapy have demonstrated synergistic effects in preclinical models and clinical trials.
• Some TKIs that normalize angiogenesis, when combined with immune checkpoint blocking antibodies, have received FDA approval.
• Active clinical trials are evaluating diverse TKI-immunotherapy combinations across various cancer types.

Conclusions:

• Combining TKIs with immunotherapy represents a promising strategy for advancing cancer therapy.
• Further research is essential to identify optimal drug combinations, dosing, and scheduling for maximizing therapeutic benefits.
• The ongoing clinical trials summarized in this review are critical for improving tangible progress in cancer care through TKI-immunotherapy combinations.