Unraveling Survival Determinants in Patients with Advanced Non-Small-Cell Lung Cancer with EGFR Exon 20 Insertions
Background: In Taiwan, lung cancer is the primary cause of cancer-related mortality. A significant proportion of lung cancer cases are linked to mutations in the epidermal growth factor receptor (EGFR) gene, with common mutations accounting for approximately 85% of these cases. However, the remaining 15% are attributed to less frequent EGFR mutations, predominantly insertions in exon 20, which constitute about 4% of all EGFR-related cases. The effectiveness of EGFR tyrosine kinase inhibitors (TKIs) can vary considerably in patients with these exon 20 insertions. Despite this clinical challenge, there have been limited large-scale studies focusing on patients with these specific EGFR mutations.
Methods: This study pooled data from several major hospitals in Taiwan to investigate the effects and clinical significance of rare EGFR mutations on patient responses to EGFR-TKIs, while also considering changes in their medication regimens over time.
Results: The study included 38 patients diagnosed with non-small-cell lung cancer who harbored EGFR exon 20 insertions. The researchers analyzed the correlations between various predictive factors and both progression-free survival (PFS), the length of time during and after treatment that a patient lives with the disease but it does not get worse, and overall survival (OS), the length of time from either the date of diagnosis or the start of treatment that patients diagnosed with the disease are still alive. The results indicated that for patients with EGFR exon 20 insertions, the median PFS was 5.15 months, and the median OS was 13 months. When examining specific treatments, the median PFS was 5.4 months for patients treated with afatinib, 5.7 months for those who received chemotherapy, and 4.3 months for those treated with first-generation EGFR-TKIs.
Conclusions: The findings of this study suggest that EGFR-TKIs may be considered as a potential alternative treatment option for patients with EGFR exon 20 insertions, particularly in situations where the currently recommended therapies, such as chemotherapy with or without the antibody amivantamab, are either not accessible or cannot be tolerated by the patient EGF816. The potential use of afatinib for specific patients within this group depends on the precise characteristics of their individual mutation and requires further investigation to determine its optimal application.