P2.14-47 Real-World Multicenter Experience of First-line Afatinib in Patients with EGFR-Mutant Advanced Non-Small Cell Lung Cancer

Abstract

Afatinib is an irreversible, second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) that has been shown to be more potent than platinum doublet chemotherapy as well as the first-generation EGFR-TKI. This study aimed to look into the efficacy, side-effects and resistance mechanisms of first-line afatinib in the real-world setting. This is a multicenter observational study of Malaysian patients with EGFR-mutant advanced non-small cell lung cancer (NSCLC) started on first-line afatinib from 1st October 2014 to 30th April 2018. Of 85 patients analyzed, EGFR mutations harbored by the tumors included exon 19 deletion in 80.0%, exon 21 L858R point mutation in 12.9%, and rare or complex EGFR mutations in 7.1%. Among the 85 patients, 18.8% had an ECOG performance status of 2-4, 29.4% had symptomatic brain metastases and 17.6% had abnormal organ function. Afatinib 40 mg or 30 mg once daily was the most common starting and maintenance doses. Only one-tenth of patients experienced severe side-effects and none had grade 4 toxicities. The objective response rate was 76.5% while the disease control rate was 95.3%. At the time of analysis, 56 (65.9%) patients had experienced disease progression (PD) with a median progression-free survival (mPFS) of 12.2 months (95% CI, 8.9-15.5 months). Only 12.5% of the PD patients developed new symptomatic brain metastases. Multivariate analysis demonstrated only patients with exon 19 deletion had significantly longer mPFS than those with rare or complex EGFR mutations (13.5 versus 9.0 months, HR, 0.31; 95% CI, 0.11-0.84; p = 0.021). The overall survival data was not mature. Of the patients who experienced PD while on afatinib, 55.3% were investigated for acquired resistance mechanisms. Exon 20 T790M mutation was detected in 42.0% of these patients. Afatinib is an effective first-line treatment for patients with EGFR-mutant advanced NSCLC with good response and disease control rates as well as long PFS even in patients with unfavorable clinical characteristics. The side-effects of afatinib were manageable and acquired T790M mutation was a common mechanism causing treatment failure.