Clinical outcomes and secondary epidermal growth factor receptor (EGFR) T790M mutation among first‐line gefitinib, erlotinib and afatinib‐treated non‐small cell lung cancer patients with activating EGFR mutations

Abstract

Gefitinib, erlotinib and afatinib are approved for first‐line treatment of advanced non‐small cell lung cancer (NSCLC) bearing an activating epidermal growth factor receptor (EGFR) mutation. However, the clinical outcomes among the three EGFR tyrosine kinase inhibitors (TKIs) are still controversial. We aimed to evaluate clinical outcomes and secondary EGFR T790M mutation among the three EGFR TKIs. From May 2014 to January 2016, a total of 301 patients received treatment with gefitinib, erlotinib or afatinib, for first‐line treatment of advanced NSCLC with an activating EGFR mutation, based on their clinicians’ choice. The median overall survival (OS) was 37.0 months. Although the baseline characteristics of patients were unequal, progression‐free survival and OS did not differ among the 3 groups. Multivariate analysis found that gefitinib (adjusted odds ratio [aOR] 3.29, 95% confidence interval [CI], 1.15–9.46, p = 0.027), EGFR TKI treatment duration more than 13 months (aOR 3.16, 95% CI, 1.20–8.33, p = 0.020), male (aOR 3.25, 95% CI, 1.10–9.66, p = 0.034), initial liver metastasis (aOR 4.97, 95% CI 1.18–20.96, p = 0.029) and uncommon EGFR mutation (aOR 0.14, 95% CI, 0.02–0.97, compared to EGFR deletion 19, p = 0.047) were independent factors for secondary T790M mutation. In real‐world practice, choosing first line EGFR TKI based on the patients’ clinical characteristics yielded good clinical outcomes. First‐line gefitinib, longer EGFR TKI treatment duration, male, initial liver metastasis and uncommon EGFR mutations may be independent factors for secondary EGFR T790M mutation.

An Observational Study of Acquired EGFR T790M-Dependent Resistance to EGFR-TKI Treatment in Lung Adenocarcinoma Patients in Taiwan

“…Our study also identified that patients with common baseline EGFR mutations of Del-19 and L858R had a higher T790M acquisition rate compared to those with uncommon baseline EGFR mutations. Lin et al also reported that uncommon EGFR mutation had less secondary T790M acquisition (adjusted OR 0.14, 95% CI, 0.02–0.97; p = 0.047) compared with del-19 of EGFR mutation ( 18 ). In addition, the previous studies showed T790M was more frequent in patients with Del-19 compared to those with L858R ( 15 , 17 , 26 – 28 ), which was also observed as a trend but without statistical significance in our study.…”

“…In particular, there were more erlotinib-treated (N = 154) and afatinib-treated patients (N = 91) in the present study. Lin et al enrolled 16 erlotinib-treated and 36 afatinib-treated patients (18). Huang et al enrolled 13 afatinib-treated patients (15).…”

“…Upon disease progression from the EGFR-TKI treatment, repeat biopsy (re-biopsy) samples were obtained for the assessment of T790M mutation from June 2013 to December 2018. Some patients were reported in prior studies (15,18).…”

“…To identify patients for subsequent osimertinib treatment, several studies have investigated the tendency of acquired T790M under first-line EGFR-TKI treatments ( 14 – 17 ). In Taiwan, two single-center studies reported different rates of T790M occurrence under the treatment of the three first-line EGFR-TKIs ( 15 , 18 ). Since afatinib was approved much later than the first-generation EGFR-TKIs, previous studies included fewer patients treated with afatinib compared to those treated with gefitinib and erlotinib.…”

Osimertinib versus afatinib in patients with T790M-positive, non-small-cell lung cancer and multiple central nervous system metastases after failure of initial EGFR-TKI treatment

“…A population-based study involving 15 medical institutes that cover a population of three million people indicated the disadvantages of pre-treatment before AFA in patients with NSCLC harboring an acquired EGFR T790M mutation [18]. However, the evidence-based trials regarding the optimal regimen in the management of cases with T790M-positive NSCLC and multiple CNS metastases remain controversial [23,26]. Within this context, evidence has indicated that neither the firstgeneration nor second-generation EGFR-TKIs distinctly improve the OS among those cases with T790M-positive NSCLC [23,27].…”