Potential of Beta-Blockers in Preventing Resistance to EGFR Inhibitors in Lung Cancer
Using beta-blockers to prevent stress hormones from binding to the immune signaling protein interleukin-6 (IL-6) might improve outcomes for patients with non–small cell lung cancer (NSCLC) relative to chemotherapy alone. This finding is based on a retrospective analysis of available patient samples and data from the phase III trials ZEST, BATTLE, and LUX-Lung3 by Monique B. Nilsson, PhD, of The University of Texas MD Anderson Cancer Center, and colleagues, which was published in Science Translational Medicine.
“The concept that beta-blockers, which are well tolerated and inexpensive, may improve responses to EGFR-targeting agents is exciting and should be tested clinically,” reported the study’s senior author John V. Heymach, MD, PhD, also of MD Anderson, in a press release.
Previous studies showed a connection between epidermal growth factor receptor (EGFR) inhibitor resistance and IL-6, which is activated by hormones such as epinephrine and norepinephrine. In mice with transplanted EGFR-mutant tumor cells, chronic stress accelerated tumor growth and promoted resistance to EGFR inhibitors.
In patients treated with EGFR inhibitors, those with higher concentrations of IL-6 in pretreatment plasma samples had an overall survival of 4.8 months, whereas those with lower concentrations had an overall survival of 11.5 months. Patients given EGFR inhibitor treatment in the LUX-Lung3 study had a median progression-free survival of 11.1 months compared with 6.9 months for patients who received chemotherapy alone. Patients who happened to be receiving beta-blockers while on treatment with EGFR inhibitors had a median progression-free survival of 13.6 months, compared with 2.5 months for those treated with chemotherapy.