P1. 15-15 Real-world Experience with Afatinib after Failure of First-Generation Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor
Background: Afatinib, a second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) is the recommended first-line treatment for patients with advanced non-small cell lung cancer harbouring sensitizing EGFR mutations. The role of afatinib after failure of first-genera...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | en |
| Published: |
Elsevier
2018
|
| Subjects: | |
| Online Access: | http://ir.unimas.my/id/eprint/22820/1/JTO%202nd%20afatinib.pdf http://ir.unimas.my/id/eprint/22820/ https://www.jto.org/article/S1556-0864(18)31905-1/fulltext |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Background: Afatinib, a second-generation epidermal growth factor
receptor (EGFR)-tyrosine kinase inhibitor (TKI) is the recommended
first-line treatment for patients with advanced non-small cell lung
cancer harbouring sensitizing EGFR mutations. The role of afatinib after failure of first-generation EGFR-TKIs is controversial.
Method: A retrospective observational study of patients with EGFR mutant advanced NSCLC receiving second-line afatinib after failure of firstgeneration EGFR-TKI in University Malaya Medical Center from 1st December 2014 to 30th April 2018.
Result: The demographic and clinical characteristics of 27 patients treated with afatinib after failure of first-generation EGFR-TKI are shown in Table 1. Twenty-three patients received gefitinib and 4 patients received erlotinib as first-line treatment. The mPFS with first-line treatment was 11.9 months. Fifteen patients had progression of disease (PD) following second-line afatinib
with mPFS of 4.2 months and median time-to-treatment failure of 5.7 months. The mPFS2 conferred by first-line first-generation EGFR-TKI and second-line afatinib was 18.4 months. The overall response rate to second-line afatinib was 18.5% (5/27) while the disease control rate as 70.3% (19/27). Two patients who had PD on first-generation EGFR-TKI due to T790M mutation received second-line afatinib while waiting for compassionate access to osimertinib. Nine of the 15 patients (69.2%) with PD on afatinib underwent investigations for resistance mechanisms. Three patients had T790M mutation, one of whom had concomitant small cell lung cancer transformation. c-MET amplification was detected in another 3 patients. One patient each had EML4-ALK rearrangement and epithelial mesenchymal transition.
Conclusion:
Afatinib conferred a modest mPFS benefit after failure of first-generation EGFR-TKI. The mPFS of sequential treatment with first-generation EGFR-TKI followed by afatinib seems longer than the mPFS of first-line afatinib in phase 3 randomised controlled trials. Apart from T790M mutation, the resistance mechanisms to second-line afatinib in our patients are more heterogenous. |
|---|