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

• Main Authors: Chai, Chee Shee, Ho, Gwo Fuang, Adlinda, Alip, Mohd Ibrahim, Abd Wahid, Matin Mellor, Abdullah, Foo, Yoke Ching, How, Soon Hin, Adel, Zaatar, Lam, Kai Seng, Leong, Kin-Wah, Low, JohnbSeng Hooi, Mastura, Md Yusof, Lee, Erica Chai Yong, Toh, Yok Yong, Liam, Chong Kin
• Format: Article
• Language: English
• Published: Springer Nature 2019
• Subjects: RC0254 Neoplasms. Tumors. Oncology (including Cancer)
• Online Access: http://ir.unimas.my/id/eprint/26798/1/Chai%2C%20Chee%20Shee.pdf; http://ir.unimas.my/id/eprint/26798/; https://bmccancer.biomedcentral.com/articles/10.1186/s12885-019-6107-1

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 T790M 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.