P1.15-15 Real-world Experience with Afatinib after Failure of First-Generation Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor

Abstract

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.