Real-world experience of first-line afatinib in patients with EGFR-mutant advanced NSCLC: a multicenter observational study

Abstract

Background This study aimed to evaluate the efficacy, side-effects and resistance mechanisms of first-line afatinib in a real-world setting. Methods This is a multicenter observational study of first-line afatinib in Malaysian patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small cell lung cancer (NSCLC). Patients’ demographic, clinical and treatment data, as well as resistance mechanisms to afatinib were retrospectively captured. The statistical methods included Chi-squared test and independent t-test for variables, Kaplan-Meier curve and log-rank test for survival, and Cox regression model for multivariate analysis. Results Eighty-five patients on first-line afatinib from 1st October 2014 to 30th April 2018 were eligible for the study. EGFR mutations detected in 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% of patients. Among these patients, 18.8% had Eastern Cooperative Oncology Group 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 were the most common starting and maintenance doses. Only one-tenth of patients experienced severe side-effects with none having 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 progression of disease (PD) with a median progression-free survival (mPFS) of 14.2 months (95% CI, 11.85–16.55 months). Only 12.5% of the progressed patients developed new symptomatic brain metastases. The overall survival (OS) data was not mature. Thirty-three (38.8%) patients had died with a median OS of 28.9 months (95% CI, 19.82–37.99 months). The median follow-up period for the survivors was 20.0 months (95% CI, 17.49–22.51 months). Of patients with PD while on afatinib, 55.3% were investigated for resistance mechanisms with exon 20 T790 M mutation detected in 42.0% of them. Conclusions Afatinib is an effective first-line treatment for patients with EGFR-mutant advanced NSCLC with a good response rate and long survival, even in patients with unfavorable clinical characteristics. The side-effects of afatinib were manageable and T790 M mutation was the most common resistance mechanism causing treatment failure.

Efficacy of afatinib in a patient with rare EGFR (G724S/R776H) mutations and amplification in lung adenocarcinoma: A case report

“…In LUX-Lung 7 and LUX-Lung 8 studies, it was found that patients treated with afatinib as both first-line treatment (compared with gefitinib) and second-line treatment (compared with erlotinib) resulted in a longer PFS or OS[ 10 , 11 ]. However, most patients with rare or complex EGFR mutations had a shorter PFS than patients with exon 19 deletion (16.0 mo vs 9.0 mo; HR, 0.34; 95%CI, 0.13-0.94, P = 0.037)[ 12 ]. In addition, it has been reported that patients aged ≥ 65 years with rare mutations have significantly longer PFS than patients aged < 65 years after receiving EGFR TKIs (median PFS: 10.5 mo vs 5.5 mo, P = 0.0320)[ 13 ].…”

Real-world Treatment Patterns in Patients with EGFR Mutation-positive NSCLC Receiving a First-Line, First- or Second-generation EGFR Tyrosine Kinase Inhibitor in South Korea and Taiwan

“…At the time of this study (2015)(2016)(2017), guidelines recommended first-line (1L) treatment of EGFRm advanced NSCLC with first-or second-generation (1G/2G) EGFR-tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib or afatinib [10][11]. Despite initial efficacy, most patients with EGFRm advanced or metastatic NSCLC treated with a 1L 1G/2G EGFR-TKI develop resistance, with disease progression occurring after a median of 8 to 16 months [12][13][14]. The EGFR T790M acquired resistance mutation has been observed in approximately 50% of patients from a meta-analysis of clinical trials [15] while rates of approximately 30% have been reported in real-world studies [16][17][18].…”

Sequential Treatment of Afatinib and Osimertinib in Patients with Advanced Non-small Cell Lung Cancer Harboring EGFR Mutations: Results from a Real-world Study in South Korea

“…The AURA-3 clinical trial demonstrated that second-line osimertinib had signi cantly greater e cacy than pemetrexed plus platinum-based therapy in advanced-stage T790M-mutated NSCLC during treatment with rst-line EGFR TKIs such as ge tinib, erlotinib, and afatinib 7 . AURA-3 reported 10.1 months of PFS on osimertinib and 4.4 months of adjustment on survival outcomes in patients with EGFR-mutated NSCLC reported that patients who received dose reductions experienced higher ORRs 19 . Another RWD study showed that dose adjustment reduced the number and intensity of several side effects, emphasizing that tailored dose modi cation could help treatment optimization and improve survival outcomes 20 .…”