Williams Cancer Institute

EGFR Inhibitors

EGFR Inhibitors

EGFR inhibitors block the epidermal growth factor receptor, which is found on the surface of some cells stimulating cell growth. There are several types of EGFR inhibitors. They can be tyrosine kinase inhibitors or monoclonal antibodies. These are used in colon, breast, lung, pancreatic, renal and head and neck cancers. Although there have been very limited studies with the combination of EGFR inhibitors and immunotherapy, theoretically, the combination should be synergistic. However, in limited studies of patients who received PD-1 inhibitors combined with a TKI EGFR inhibitor a significant increase in side effects with modest increase in survival was observed. It is unclear what synergy may surface with other immunotherapies in the future. In addition, Schoenfeld, et al. published an article titled “Severe Immune Related Adverse Events Are Common with Sequential PD-(L)1 Blockade and Osimertinib” in Annals of Oncology, March 7, 2019. This article cites a human study which showed that patients first placed on a PD-1 or PD-L1 inhibitor, followed by the EGFR inhibitor osimertinib (Tagrisso), had increased adverse immune side effects. This was greatest if the drugs were started less than 3 months apart. The duration of use of the PD-1/PD-L1 inhibitor did not seem to matter. Of note, if the EGFR inhibitor was used first, no significant immune side effects were seen. Again, systemic use of these drugs, even when not done at the same time, can result in increased side effects. This begs the question, how would systemic EGFR receptor inhibitors work with intra- tumoral injection of PD-1/PD-L1 inhibitors?

Reference: Jason R. Williams, 15 Oct 2019, The Immunotherapy Revolution: The Best New Hope For Saving Cancer Patients’ Lives, https://williamscancerinstitute.com/the-immunotherapy-revolution

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