EGFR exon 20 insertion mutations in Chinese advanced non-small cell lung cancer patients: Molecular heterogeneity and treatment outcome from nationwide real-world study

Objectives: To describe the treatment patterns and outcomes of Chinese non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations in real-world as EGFR ex20ins consist of a diverse group of mutations with limited information on the clinical outcome of these patients treated with chemotherapy or EGFR tyrosine kinase inhibitors (TKIs).

Materials and methods: Real-world treatment outcomes of Chinese NSCLC patients harboring EGFR ex20ins were retrospectively analyzed based on medical records at different institutions and detailed web-based patient questionnaires.

Results: Between March 17, 2018 and December 20, 2018, 165 advanced EGFR ex20ins NSCLC patients treated in 99 hospitals from 26 different regions in China were analyzed. Thirty-nine different molecular variants of EGFR ex20ins were identified with V769_D770insASV being the most common (23.0 %). Central nervous system (CNS) metastasis occurred in 23.0 % of patients at the time of baseline diagnosis. Median progression-free survival (PFS) was significantly longer in patients who received first-line platinum-based chemotherapy (6.4 m; 95 % CI: 5.7-7.1) than all-generation EGFR TKIs (2.9 m; 95 %CI: 1.5-4.3; P < 0.001) or 1st-generation EGFR TKIs (2.0 m; 95 %CI: 0.2-3.8; P < 0.001). Median PFS was numerically longer in patients who received second-line chemotherapy (4.0 m; 95 %CI: 3.2-4.8) than those received second-line EGFR TKIs (2.0 m; 95 %CI: 1.1-2.9; P = 0.342). Patients with CNS metastasis had numerically shorter median PFS than those without CNS metastasis when treated with 1st-line chemotherapy (3.6 m; 95 %CI: 0-8.0 vs. 6.5 m; 95 %CI: 4.9-8.1; P = 0.645) or 1st-line EGFR TKIs (2.0 m; 95 %CI: 0.8-3.2 vs. 2.9 m; 95 %CI: 2.1-3.7; P = 0.058).

Conclusion: Chemotherapy is superior to current approved EGFR TKIs as 1st- or 2nd-line treatment of EGFR ex20ins mutations. CNS metastasis conferred numerically shorter PFS with chemotherapy or EGFR TKIs treatment. Targeted agent against EGFR ex20ins with CNS activity is urgently needed.