PD-1 Inhibitors Improve Survival in Patients With Advanced EGFR-Mutant NSCLC After TKI Resistance

After tyrosine kinase inhibitor (TKI) failure, programmed cell death protein 1 (PD-1) inhibitors improved survival more in some types of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC), according to a study published in Annals of Translational Medicine. 

“EGFR-TKIs have shown great treatment efficacy for advanced EGFR-mutant NSCLC and are recommended as first-line treatment in the National Comprehensive Cancer Network guidelines,” wrote researchers from China. “However, acquired drug resistance to various EGFR-TKIs inevitably develops in almost all such patients.”

The study included 102 patients with EGFR-mutant NSCLC who received PD-1 inhibitors after developing resistance to EGFR-TKIs. Researchers were interested in subpopulations of patients who derived the most benefit. 

PD-1 inhibitors provided better survival in patients with EGFR^L858R and patients who were EGFR^T790M-negative, according to the study. Specifically, progression-free survival was 6.4 months in the EGFR^L858R group compared with 3.5 months in the EGFR^D19 group. Median progression-free survival was 6.47 months in the EGFR^T790M-negative group compared with 3.20 months in the EGFR^T790M-positive group. Median overall survival in all patients was 10.70 months.

“There was a trend towards improved progression-free survival and overall survival with combination therapy,” researchers reported.

The incidence of grade-3 through -5 treatment-related adverse events was 19.6% and did not vary with mutation subtype. Meanwhile, the incidence of grade-3 through -5 immune-related adverse events was 10.3% in the EGFR^D19 group compared with 5.9% the EGFR^L858R group, and 10% in the EGFR^T790M-negative group compared with 2.6% in the EGFR^T790M-positive group.

“Our real-world study increased the population size and obtained a similar survival outcome compared [with] clinical trials,” researchers wrote.

Reference:
Zhou C, Wang Z, Fu C, Tao H, Liu C. The efficacy and safety of PD-1 inhibitors for EGFR-mutant non-small cell lung cancer after tyrosine kinase inhibitor failure: a retrospective real-world cohort study. Ann Transl Med. Published online February 15, 2023. doi:10.21037/atm-22-6272