LAUSR

Abstract Background Afatinib is an irreversible second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) while gefitinib or erlotinib are reversible first-generation EGFR-TKIs. Methods A retrospective analysis of patients with EGFR mutant advanced lung adenocarcinoma receiving first-line afatinib versus gefitinib or erlotinib at University Malaya Medical Centre from 1st January 2015 to 31th December 2018. Results Of 113 patients, 24 (21.2%) received afatinib, 63 (55.8%) received gefitinib and 26 (23.0%) received erlotinib in first-line setting. Their demographic and clinical characteristics are shown in the table. Afatinib was used significantly more frequently in patients with rare or complex EGFR mutations (p = 0.005), and more often in patients with symptomatic brain metastases. The median progression-free survival (mPFS) of patients treated with afatinib (13.1 months) was longer than that of patients treated with gefitinib (10.9 months) or erlotinib (7.8 months) (p = 0.479). Patients receiving afatinib had consistently longer PFS than patients receiving gefitinib for the first 17 months and erlotinib for the first 20 months. The overall response rate was higher in patients on afatinib (75.0%) than those on gefitinib (63.5%) or erlotinib (53.8%). There was no difference in the disease control rate. Three patients (2.7%) had severe side-effects while on EGFR-TKI. Of two patients on afatinib, one had grade-3 diarrhea while another had grade 3 stomatitis, rash and paronychia. One patient had grade 3 rash on gefitinib. Table . 487P Clinical characteristic of 113 patients on first-line EGFR-TKI Characteristics, No (%) Afatinib (24) Gefitinib (63) Erlotinib (26) p-value Symp brain mets No Yes 17 (70.8) 7 (29.2) 53 (84.1) 10 (15.9) 22 (84.6) 4 (15.4) 0.181 EGFR subtype 19 del 21 L858R Rare/complex 16 (66.7) 2 (8.3) 6 (25.0) 39 (61.9) 20 (31.7) 4 (6.3) 22 (84.6) 3 (11.5) 1 (3.8) 0.005 Side-effect grade 1-2 grade 3 22 (91.7) 2 (8.3) 62 (98.4) 1 (1.6) 26 (100) 0 0.007 Objective response Yes No 18 (75.0) 6 (25.0) 40 (63.5) 23 (36.5) 14 (53.8) 12 (46.2) 0.298 Disease control Yes No 23 (95.8) 1 (4.2) 59 (93.7) 4 (6.3) 24 (92.3) 2 (7.7) 0.872 Median PFS Months Event, No. (%) 13.1 19 (79.2) 10.9 49 (77.8) 7.8 19 (73.1) 0.479 Conclusions Patients receiving first-line afatinib demonstrated longer mPFS than those on first-line gefitinib or erlotinib. The lack of statistical significance in this study is because of the small number of patients treated with afatinib, more frequent rare or complex EGFR mutations and more symptomatic brain metastases among afatinib treated patients. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.