Dataset Information

Preventing and treating brain metastases with three first-line EGFR-tyrosine kinase inhibitors in patients with EGFR mutation-positive advanced non-small cell lung cancer.

ABSTRACT:

Introduction

Brain metastases (BM) are common in advanced non-small cell lung cancer (NSCLC), and the prognosis is poor with few therapeutic options. This study evaluated the efficacy of three epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in preventing and treating BM in patients with EGFR mutation-positive advanced NSCLC.

Methods

Patients with EGFR mutation-positive advanced NSCLC who visited a tertiary referral center from 1 December 2013 to 30 November 2017 were analyzed retrospectively. They received gefitinib, erlotinib, or afatinib until disease progression, death, or intolerable adverse events. The cumulative incidence of subsequent BM of initial non-BM patients, progression-free survival (PFS), and overall survival (OS) of the BM and non-BM patients were estimated and compared using the Kaplan-Meier and log-rank tests.

Results

306 NSCLC patients were enrolled, with 116, 75, and 115 receiving first-line gefitinib, erlotinib, and afatinib, respectively. The afatinib group had a better PFS [12.7 versus 9.8 months; hazard ratio (HR) 0.59, p?=?0.001] and OS (39.1 versus 22.0 months; HR 0.64, p?=?0.035) than the gefitinib group. Afatinib tended to provide better BM prevention than gefitinib (BM cumulative incidence, HR 0.49; 95% confidence interval 0.34-0.71, p?p?p?=?0.015) than those without initial BM. Among the former, there were no differences in median PFS (p?=?0.34) and median OS (p?=?0.46) in the three EGFR-TKI groups.

Conclusions

Our data suggested that, compared with gefitinib, afatinib provided better benefits significantly in terms of PFS and OS. Both had the same effectiveness in preventing subsequent BM.

SUBMITTER: Su PL

PROVIDER: S-EPMC6156208 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Preventing and treating brain metastases with three first-line EGFR-tyrosine kinase inhibitors in patients with EGFR mutation-positive advanced non-small cell lung cancer.

Su Po-Lan PL Wu Yi-Lin YL Chang Wei-Yuan WY Ho Chung-Liang CL Tseng Yau-Lin YL Lai Wu-Wei WW Su Wu-Chou WC Lin Chien-Chung CC Yang Szu-Chun SC

Therapeutic advances in medical oncology 20180925

<h4>Introduction</h4>Brain metastases (BM) are common in advanced non-small cell lung cancer (NSCLC), and the prognosis is poor with few therapeutic options. This study evaluated the efficacy of three epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in preventing and treating BM in patients with EGFR mutation-positive advanced NSCLC.<h4>Methods</h4>Patients with EGFR mutation-positive advanced NSCLC who visited a tertiary referral center from 1 December 2013 to 30 November ...[more]

PMID: 30263066

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Project description:Tyrosine kinase inhibitors (TKIs) against the human epidermal growth factor receptor (EGFR) are now standard treatment in the clinic for patients with advanced EGFR mutant non-small-cell lung cancer (NSCLC). First-generation EGFR TKIs, binding competitively and reversibly to the ATP-binding site of the EGFR tyrosine kinase domain, have resulted in a significant improvement in outcome for NSCLC patients with activating EGFR mutations (L858R and Del19). However, after a median duration of response of ~12?months, all patients develop tumor resistance, and in over half of these patients this is due to the emergence of the EGFR T790M resistance mutation. The second-generation EGFR/HER TKIs were developed to treat resistant disease, targeting not only T790M but EGFR-activating mutations and wild-type EGFR. Although they exhibited promising anti-T790M activity in the laboratory, their clinical activity among T790M+ NSCLC was poor mainly because of dose-limiting toxicity due to simultaneous inhibition of wild-type EGFR. The third-generation EGFR TKIs selectively and irreversibly target EGFR T790M and activating EGFR mutations, showing promising efficacy in NSCLC resistant to the first- and second-generation EGFR TKIs. They also appear to have lower incidences of toxicity due to the limited inhibitory effect on wild-type EGFR. Currently, the first-generation gefitinib and erlotinib and second-generation afatinib have been approved for first-line treatment of metastatic NSCLC with activating EGFR mutations. Among the third-generation EGFR TKIs, osimertinib is today the only drug approved by the Food and Drug Administration and the European Medicines Agency to treat metastatic EGFR T790M NSCLC patients who have progressed on or after EGFR TKI therapy. In this review, we summarize the available post-progression therapies including third-generation EGFR inhibitors and combination treatment strategies for treating patients with NSCLC harboring EGFR mutations and address the known mechanisms of resistance.

Project description:BackgroundFew studies have compared the efficacy of the irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), afatinib, with that of reversible EGFR-TKIs. Therefore, this study assessed the effectiveness of afatinib, erlotinib, and gefitinib in terms of OS (overall survival) and progression-free survival (PFS) in EGFR mutation-positive advanced non-small cell lung cancer (NSCLC) patients.MethodsPatients with EGFR mutation-positive advanced NSCLC who sought treatment from December 2013 to June 2018, at a tertiary referral center were retrospectively analyzed. These patients were treated with afatinib or a reversible EGFR-TKI (erlotinib or gefitinib) until disease progression, intolerable adverse events, or death. The Kaplan-Meier and log-rank tests were then used to compare the OS and PFS of the patients. We further analyzed the survival differences among the subgroup of patients without brain metastases.ResultsOf the 363 patients enrolled, 134 and 229 received first-line afatinib and first-line reversible EGFR-TKI, respectively. Those given afatinib had better OS (39.3 vs. 26.0 months; HR 0.65, P = 0.033) and PFS (14.1 vs.11.2 months; HR 0.58, P < 0.001). Of the 246 patients without brain metastases, 93 and 153 received first-line afatinib and a first-line reversible EGFR-TKI, respectively. Those given afatinib had a better OS (52.6 vs. 24.9 months; HR 0.62, P = 0.0030) and PFS (17.7 vs. 11.1 months; HR 0.51, P < 0.001). The survival benefit was more significant in the subgroup of patients with L858R substitutions.ConclusionsThe results indicated that afatnib resulted in significantly better OS and PFS than gefitnib and erlotinib for EGFR mutation-positive advanced NSCLC patients without brain metastases.Key pointsSignificant findings of the study Afatnib resulted in significantly better overall survival and progression-free survival than gefitnib and erlotinib for EGFR mutation-positive advanced non-small cell lung cancer patients without brain metastases. What this study adds This study helps fill the gap in our limited understanding of the differences in the efficacy of the irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), afatinib, with that of reversible EGFR-TKIs.

Project description:BackgroundData from clinical trials and real-world studies show that afatinib is effective in treating non-small cell lung cancer (NSCLC) harboring activating mutations in the epidermal growth factor receptor (EGFR) gene. A previous analysis of patients enrolled in the Korean Academy of Tuberculosis and Respiratory Disease (KATRD) EGFR cohort showed that first-line afatinib was well tolerated and effectiveness results were encouraging. At the time of the previous analysis, survival data were not mature. Here we briefly present updated survival data from the cohort.MethodsThe study was a retrospective, multicenter (15 sites) review of electronic records of Korean adult patients (aged >20 years) with advanced EGFR mutation-positive NSCLC who initiated first-line afatinib (N=421). Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier survival curves.ResultsOverall, median PFS was 20.2 months and median OS was 48.6 months. OS rates at 36 and 60 months were 60.1% and 42.3%, respectively. Presence vs. absence of baseline brain metastases was associated with significantly reduced median PFS (14.9 vs. 28.0 months; P<0.001) and median OS (32.2 vs. 65.6 months; P<0.001). The presence of common baseline EGFR mutations (Del19, L858R) was associated with significantly prolonged median OS (49.6 vs. 30.1 months; P=0.017). In patients stratified by the presence/absence of T790M EGFR mutation, the T790M mutation was associated with significantly reduced median PFS (P=0.0005) but there was no significant difference between groups in survival (P=0.263). There were no significant differences in PFS or OS for patients stratified by afatinib dose reduction or by age group (<70 vs. ≥70 years).ConclusionsAfatinib was effective in Korean patients with EGFR mutation-positive NSCLC with median OS over 4 years. The presence of baseline brain metastases and/or uncommon EGFR mutations were associated with reduced survival. In the absence of baseline brain metastases, median OS was more than 5 years.

Dataset Information

Preventing and treating brain metastases with three first-line EGFR-tyrosine kinase inhibitors in patients with EGFR mutation-positive advanced non-small cell lung cancer.

Introduction

Methods

Results

Conclusions

Publications

Preventing and treating brain metastases with three first-line EGFR-tyrosine kinase inhibitors in patients with EGFR mutation-positive advanced non-small cell lung cancer.

Similar Datasets

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