1362P Clinical and real-world outcomes in patients with epidermal growth factor receptor (EGFR) exon 20 insertions in non-small cell lung cancer (NSCLC): A meta-analysis

Abstract

In EGFR-mutant NSCLC patients, approximately 0.5-4% have exon 20 insertions. Approved EGFR tyrosine kinase inhibitors (TKIs) are ineffective in patients with exon 20 insertions. We reviewed and synthesized published evidence for outcomes in these patients. A systematic literature review was performed following PRISMA guidelines. Populations of interest were EGFR-mutant NSCLC patients with exon 20 insertions, including subgroups analyses in larger NSCLC cohorts. Outcomes included overall survival (OS), progression-free survival (PFS), and overall response rate (ORR), all weighted by number of patients in the meta-analysis. Of 3920 records, 5 clinical and 32 real-world evidence (RWE) studies fulfilled inclusion criteria. Meta-analyzed real-world outcomes for treatment groups (TKI, chemotherapy +/- TKI, and immuno-oncology (IO) agents) were generally suboptimal (Table). Most RWE studies reported outcomes for cohorts with patients at various lines of therapy. In clinical studies, TAK-788 showed promising results with a 43% confirmed ORR (n=12/28) and a 7.3-month median PFS in refractory patients; ORR for JNJ-372 was 30% in TKI-naïve patients (22% confirmed, n =27 ); poziotinib, luminespib, afatinib, and cisplatin/pemetrexed resulted in <20% ORR. In clinical studies that reported brain metastases, the mean rate was 25% (range, 0-53%).Table: 1362POutcomes in EGFR-mutant NSCLC patients with exon 20 insertions*Median OS, months (n)Median PFS, months (n)ORR, % (n)All treatments16.2 (666)4.8 (707)19.8% (684)TKI12.6 (210)4.0 (317)16.1% (409)Chemotherapy +/- TKI18.6 (330)5.5 (355)27.5% (242)IO agent7.5 (29)3.2 (26)10.0% (30)*Includes a mixture of newly diagnosed and RR patients as the majority of studies did not report outcomes by line of therapy Open table in a new tab *Includes a mixture of newly diagnosed and RR patients as the majority of studies did not report outcomes by line of therapy Despite recent treatment advances in EGFR-mutant NSCLC, real-world outcomes remain poor for patients harboring exon 20 insertions. Several agents, currently undergoing clinical evaluation, may help alleviate unmet needs.