Osimertinib for Chinese advanced non-small cell lung cancer patients harboring diverse EGFR exon 20 insertion mutations

Abstract

Objectives: Epidermal growth factor receptor (EGFR) exon 20 insertion (ex20 ins) mutations are generally associated with de novo resistance to first- or second-generation EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC). However, the real efficacy of osimertinib for this subset remains elusive. We performed this study to investigate the real efficacy of osimertinib for Chinese advanced NSCLC patients harboring EGFR ex20 ins mutations.

Materials and methods: We retrospectively collected data of metastatic NSCLC patients with EGFR ex20 ins mutations who were treated with osimertinib 80 mg or 160 mg once daily in our center from June 2017 to May 2020. Progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) were assessed.

Results: A total of 62 cases with EGFR ex20 ins mutations were included, and the major insertion variant was D770_N771insSVD and V769_D770insASV (45.1 %). Concurrent TP53 mutation was most commonly observed (59.7 %). Four patients showed partial response, 29 cases with stable disease and 29 showed progressive disease as best response to osimertinib (ORR: 6.5 %, DCR: 53.2 %). The median PFS (mPFS) in total patients was 2.3 (95 %CI, 1.5-3.1) months. Patients harboring A763_Y764insFQEA/D770delinsGY variants showed numerically longer mPFS than those with other variants (4.2 vs. 2.2 months, P = 0.164). Patients who failed to osimertinib and occurred extracranial progression showed similar mPFS to those with intracranial progression (2.3 vs. 1.9 months, P = 0.142). Median PFS was not significantly different between patients who received osimertinib 80mg or 160mg once daily (2.5 vs. 1.3 months, P = 0.161), either with no significance when it used in fist-line setteing or bove (3.0 vs. 2.2 months, P = 0.639).

Conclusion: The unique insertion variant A763_Y764insFQEA and D770delinsGY might better respond to osimertinib than other ex20 ins subtypes. Osimertinib either 80 mg or 160 mg once daily showed less activity in Chinese NSCLC patients harboring diverse EGFR ex20 ins mutations.

Keywords: EGFR exon 20 insertion mutations; Non-small cell lung cancer; Osimertinib; Tyrosine kinase inhibitor.