OBJECTIVES

Epidermal growth factor receptor (EGFR) exon-20 non-small-cell lung cancer (NSCLC) is a complex disease driven by diverse variants. With the rapid increase in drug development for patients with this disease, it is becoming increasingly important to identify these variants to optimize outcomes. Although commonly used, single-gene polymerase chain reaction (sgPCR) tests are limited for detecting all EGFR exon-20 insertion (ex20ins) variants. Next-generation sequencing (NGS) testing can detect all ex20ins variants allowing for more patients to be accurately identified and appropriately treated. The objective is to understand how testing with NGS versus sgPCR impacts long-term outcomes for patients with EGFR ex20ins NSCLC.

METHODS

A Markov model considered two identical cohorts with EGFR ex20ins NSCLC; one cohort underwent NGS and the other sgPCR. Patients correctly identified as having ex20ins received platinum-based chemotherapy (PBC) followed by mobocertinib or amivantamab upon relapse. Patients incorrectly identified as with no ex20ins received first- and second-line PBC, immuno-oncology (IOs) agents, classic EGFR tyrosine kinase inhibitors (TKIs), or non-PBC (e.g., docetaxel). NGS was assumed to detect 90%-100% of exon20ins variants. Ex20ins variants detectability of sgPCR (12%-59%) was from a retrospective analysis of one clinical trial and three real-world datasets. The efficacy of PBC, IOs, TKIs, and non-PBC was from a retrospective analysis of real-world data using the United States Flatiron database. The efficacy of mobocertinib and amivantamab post-PBC was from their respective clinical trials. Life years were calculated from diagnosis until death.

RESULTS

With varying the accuracy of NGS and sgPCR, and treatment patterns after diagnosis, the average life years associated with NGS ranged from 2.97 to 3.26 vs. 1.62 to 2.85 with sgPCR.

CONCLUSIONS

NGS can improve the detection of ex20ins variants and is associated with additional life years versus sgPCR. With the development of new targeted therapies, understanding the impact PCR detection limitations on outcomes is becoming more important.