Unleashing the power of immunotherapy and targeted therapy combinations: Advancing cancer care or discovering unknown toxicities?

Objective: The purpose of this review was to summarize the triumphs and pitfalls of tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor (ICI) combinations. A literature review of PubMed was conducted and studies were included if they were classified as a clinical trial and assessed TKI and ICI combinations for solid tumor malignancies. Dates of literature search included January 1, 1988 through September 22, 2019. In the past decade, TKI and ICI monotherapy strategies have changed the management of many advanced solid tumors through their unique mechanisms of action. Preclinical data suggests that TKIs may be able to sensitize tumors to ICI therapy via direct and indirect pathways; however, optimal mechanisms to support various TKI and ICI combinations have yet to be determined. The FDA recently approved TKI and ICI combinations for renal cell carcinoma, endometrial carcinoma, and melanoma. Several other tumor types currently have TKI and immunotherapy combinations under investigation with mixed results. Dual therapy with TKIs and immunotherapy have the potential to be synergistic and improve patient outcomes; however, careful consideration will need to be taken in regard to what TKI and immunotherapy are combined.

Conclusions: Future research will be needed to determine appropriate sequencing of TKIs and ICIs after progression on combination therapy. Continued research is necessary to determine optimal dual TKI and immunotherapy options.