First- or second-generation epidermal growth factor receptor tyrosine kinase inhibitors in a large, real-world cohort of patients with non-small cell lung cancer

Allen Chung-Cheng Huang; Chi-Hsien Huang; Jia-Shiuan Ju; Tzu-Hsuan Chiu; Pi-Hung Tung; Chin-Chou Wang; Chien-Ying Liu; Fu-Tsai Chung; Yueh-Fu Fang; Yi-Ke Guo; Chih-Hsi Scott Kuo; Cheng-Ta Yang

doi:10.1177/17588359211035710

First- or second-generation epidermal growth factor receptor tyrosine kinase inhibitors in a large, real-world cohort of patients with non-small cell lung cancer

Ther Adv Med Oncol. 2021 Jul 31:13:17588359211035710. doi: 10.1177/17588359211035710. eCollection 2021.

Affiliations

¹ Division of Thoracic Oncology, Department of Thoracic Medicine, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Gueishan.
² Division of Pulmonary & Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Niaosung.
³ Data Science Institute, Department of Computing, Imperial College London, London, UK.
⁴ Division of Thoracic Oncology, Department of Thoracic Medicine, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, No 199, Tun-Hwa Nr Rd, Taipei, Gueishan, 333.
⁵ Division of Thoracic Oncology, Department of Thoracic Medicine, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taiyuan.

Abstract

Background: There are limited comparisons of first- and second-generation EGFR tyrosine kinase inhibitors (TKIs) in large, real-world cohorts of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations.

Methods: Patients with advanced NSCLC (N = 612) with common EGFR mutations receiving first-line gefitinib/erlotinib and afatinib were grouped and propensity-score matched. Progression-free survival (PFS), overall survival (OS) and secondary T790M mutations were analyzed.

Results: The gefitinib/erlotinib and afatinib groups each contained 206 patients after matching. Compared with gefitinib/erlotinib, patients receiving afatinib achieved longer median PFS (16.3 versus 14.2 months; log-rank test p = 0.020) and had a lower risk of progression [hazard ratio (HR) 0.73 (95% confidence interval (CI), 0.57-0.94); p = 0.017]. Median OS (37.3 versus 34.2 months; log-rank test p = 0.500) and reduction in risk of death [HR 0.89 (95% CI, 0.65-1.23); p = 0.476] did not differ significantly between groups. T790M positivity was significantly higher in the gefitinib/erlotinib than afatinib group (70.9% versus 44.6%, p < 0.001). Multivariate analysis demonstrated that afatinib was independently associated with lower T790M positivity [odds ratio (OR) 0.27 (95% CI, 0.14-0.53); p < 0.001], whereas ⩾12 months PFS after EGFR-TKI treatment [OR 3.00 (95% CI, 1.56-5.98); p = 0.001] and brain metastasis [OR 2.12 (95% CI, 1.08-4.26); p = 0.030] were associated with higher T790M positivity. Sequential third-generation EGFR-TKI treatment was administered to 63 patients, in whom median OS after the second-third-generation and first-third-generation EGFR-TKI sequences were 38.8 and 29.1 months, respectively.

Conclusion: Compared with gefitinib/erlotinib, afatinib had a higher treatment efficacy and a lower secondary T790M positivity in a large, real-world cohort of Asian patients with EGFR-mutated NSCLC.

Keywords: EGFR mutation; NSCLC; afatinib; erlotinib; gefitinib; real world.