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

• Main Authors: Ho, Gwo Fuang, Chai, Chee Shee, Alip, Adlinda, A. Wahid, Mohd Ibrahim, Abdullah, Matin Mellor, Foo, Yoke Ching, How, Soon Hin, Zaatar, Adel, Lam, Kai Seng, Leong, Kin Wah, Low, John Seng Hooi, Md Yusof, Mastura, Lee, Erica Chai Yong, Toh, Yok Yong, Liam, Chong Kin
• Format: Article
• Language: English; English
• Published: BioMed Central Ltd. 2019
• Subjects: L Education (General); RC Internal medicine; RC731 Specialties of Internal Medicine-Diseases of The Respiratory System
• Online Access: http://irep.iium.edu.my/86185/1/HSH2020.pdf; http://irep.iium.edu.my/86185/7/Scopus%20-%20Document%20details.pdf; http://irep.iium.edu.my/86185/; https://bmccancer.biomedcentral.com/articles/10.1186/s12885-019-6107-1; https://doi.org/10.1186/s12885-019-6107-1
• Institution: Universiti Islam Antarabangsa Malaysia

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.