Comparison of pattern of disease progression and prevalence of acquired T790M mutation in Malaysia patients with EGFR mutant lung adenocarcinoma upon failure of first-line afatinib, gefitinib and erlotinib

• Main Authors: Chai, Chee Shee, Lin, O. Po, Liam, Chong Kin, Pang, Yong Kek, Ho, G. F., Alip, A., Wong, Chee Kuan, Poh, Mau Ern, Tan, Jiunn Liang
• Format: E-Article
• Language: English
• Published: Oxford university press 2019
• Subjects: RC0254 Neoplasms. Tumors. Oncology (including Cancer)
• Online Access: http://ir.unimas.my/id/eprint/28062/1/ESMO%202019%202.pdf; http://ir.unimas.my/id/eprint/28062/; https://doi.org/10.1093/annonc/mdz437.020
• Institution: Universiti Malaysia Sarawak

Abstract Background Patients receiving first-line afatinib, gefitinib or erlotinib for epidermal growth factor receptor (EGFR) mutant advanced non-small cell lung cancer develop progression of disease (PD) after an average of 9-13 months. Methods A retrospective analysis of PD pattern and prevalence of acquired T790M mutation among patients failing first-line afatinib versus gefitinib or erlotinib at University Malaya Medical Centre from 1st January 2015 to 31th December 2018. Results Of 87 patients who developed PD while on first-line EGFR-tyrosine kinase inhibitor (TKI) treatment, 19 (21.8%) were on afatinib, 49 (56.3%) were on gefitinib, and 19 (21.8%) were on erlotinib. The median progression-free survival (mPFS) of these patients is as shown in the table. Of 20 patients (23.0%) who developed new symptomatic brain metastases, one (5.0%) had new leptomeningeal metastases, three (15.0%) had both new leptomeningeal metastases and solid brain metastases, and the remaining 16 (80.0%) had new solid brain metastases only. New leptomeningeal metastases occurred in one patient treated with afatinib and three patients treated with gefitinib. Forty-nine patients (56.3%) were investigated for acquired T790M mutation either by plasma biopsy or tissue biopsy or both. The prevalence of acquired T790M mutation was 61.2%. There was no difference in the pattern of PD or prevalence of acquired T790M mutation among patients treated with afatinib, gefitinib or erlotinib. Conclusions New leptomeningeal metastases were uncommon in patients receiving first-line EGFR-TKI. The choice of first-line first- or second generation EGFR-TKI did not influence the pattern of PD and prevalence of acquired T790M mutation. However, patients receiving afatinib appeared to have longer mPFS than those on gefitinib or erlotinib.