# Unraveling Survival Determinants in Patients with Advanced Non-Small-Cell Lung Cancer with EGFR Exon 20 Insertions

## TL;DR

This study examines survival outcomes in lung cancer patients with rare EGFR mutations, finding that EGFR-TKIs may offer treatment benefits in specific cases.

## Contribution

The study provides insights into treatment responses for EGFR exon 20 insertion mutations, a less understood subset of lung cancer.

## Key findings

- Median progression-free survival was 5.15 months for patients with EGFR exon 20 insertions.
- Afatinib showed a median PFS of 5.4 months, slightly better than chemotherapy and first-generation EGFR-TKIs.
- Overall survival reached 13 months, suggesting potential for EGFR-TKIs as alternative treatments.

## Abstract

Background: Lung cancer is the leading cause of cancer-related death in Taiwan. It is often associated with mutations in the epidermal growth factor receptor (EGFR) gene, with common mutations accounting for approximately 85% of all EGFR-related cases. However, the remaining 15% are caused by uncommon mutations in EGFR, mainly insertions in exon 20 (about 4%). The response to EGFR tyrosine kinase inhibitors (TKIs) can vary markedly with exon 20 insertions. However, few prior large-scale studies have examined patients with these EGFR mutations. Methods: This study combines the databases of several large hospitals in Taiwan to analyze the effects and clinical significance of rare EGFR mutations on responses to EGFR-TKIs, considering the changes in medication. Results: This study enrolled 38 patients with non-small-cell lung cancer and EGFR exon 20 insertions. It assessed the correlations of various predictors with progression-free survival (PFS) and overall survival (OS). It showed that among those with EGFR exon 20 insertions, the median PFS was 5.15 months, and OS reached 13 months. The median PFS was 5.4 months for afatinib, 5.7 months for chemotherapy, and 4.3 months for first-generation EGFR-TKIs. Conclusions: EGFR-TKIs may be considered as an alternative treatment option for patients with EGFR exon 20 insertions in cases where the currently recommended therapies, such as chemotherapy with or without amivantamab, are either unavailable or intolerable. The potential use of afatinib for specific patients in this context depends on the precise characteristics of their mutation and remains to be determined.