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Outcomes of adjuvant epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment for EGFR-mutant non-small-cell lung cancer: a propensity-score analysis.

ABSTRACT: Small molecule tyrosine kinase inhibitors (TKIs) have transformed the management of advanced non-small-cell lung cancer (NSCLC) harboring activating epithelial growth factor receptor (EGFR) mutations, while the efficacy of TKIs in the adjuvant setting remains unclear. We collected the data of 209 EGFR-mutant NSCLC patients receiving complete resection from 2010 to 2013. Study end points were disease-free survival (DFS) and overall survival (OS). Among the eligible patients, 41 (19.6%) received EGFR TKIs in the adjuvant treatment. The 3-year DFS of adjuvant EGFR TKIs treatment group (70.5%, 95% CI, 54.6-86.4%) was significantly superior that control group (50.2%, 95% CI, 40-60.4%; log-rank P?=?0.014). TKIs treatment (HR, 0.51; 95% CI, 0.29-0.97; P?=?0.04) was significantly associated with improved DFS in multivariate Cox analysis. No significant difference was observed in 3-year OS between two groups (73.1% [58.0-88.2%] vs 61.8% [52.2-71.4%], log-rank P?=?0.21). Propensity-score matching further confirmed that adjuvant TKIs treatment extended the DFS (log-rank P?=?0.024), but did not improve OS (log-rank P?=?0.40). Our analysis revealed that adjuvant EGFR TKIs treatment was beneficial for early-stage NSCLC patients harboring activating EGFR mutations after complete resection.

SUBMITTER: Zhao S

PROVIDER: S-EPMC5599620 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Outcomes of adjuvant epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment for EGFR-mutant non-small-cell lung cancer: a propensity-score analysis.

Zhao Shufen S Ma Ge G Guo Jing J Ding Aiping A Wang Shasha S Yu Guohong G Chen Lei L Yuan Yonggang Y Xiao Wenjing W

Scientific reports 20170914 1

Small molecule tyrosine kinase inhibitors (TKIs) have transformed the management of advanced non-small-cell lung cancer (NSCLC) harboring activating epithelial growth factor receptor (EGFR) mutations, while the efficacy of TKIs in the adjuvant setting remains unclear. We collected the data of 209 EGFR-mutant NSCLC patients receiving complete resection from 2010 to 2013. Study end points were disease-free survival (DFS) and overall survival (OS). Among the eligible patients, 41 (19.6%) received E ...[more]

PMID: 28912511

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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:BackgroundRecent studies have demonstrated benefits from adjuvant tyrosine-kinase inhibitors (TKIs) compared with chemotherapy in non-small cell lung cancer. We launched a multi-center retrospective study to evaluate the efficacy and toxicity of adjuvant TKIs with or without chemotherapy in epidermal growth factor receptor (EGFR)-mutant stage III-pN2 lung adenocarcinoma.MethodsTwo hundred and seventy-four consecutive cases with stage III-pN2 lung adenocarcinoma and complete resection have been investigated. Clinic-pathologic characteristics, adjuvant treatments, long-term survivals, and toxicities were documented. Risk factors of distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were evaluated.ResultsThere were 52 (19.0%) patients treated with adjuvant TKIs alone, 199 (72.6%) with adjuvant chemotherapy alone, and 23 (8.4%) with both. After a median follow-up time of 29 months, the two-year DMFS, DFS, and OS was 61.2%, 54.1%, and 91.2%, respectively. According to univariable analyses, the risk factors were lymphovascular invasion (p < 0.001), extranodal extension (p = 0.005), and adjuvant systemic therapy (p = 0.006) for DMFS, EGFR mutation type (p = 0.025), lymphovascular invasion (p = 0.013), extranodal extension (p = 0.004), and adjuvant systemic therapy (p < 0.001) for DFS, and EGFR mutation type (p < 0.001) for OS. Multivariable analyses indicated that the independent prognostic factors were adjuvant systemic therapy (TKIs vs. TKIs+chemotherapy, Harzard ratio (HR) = 0.40; p = 0.036; TKIs vs. chemotherapy, HR = 0.38; p = 0.004), lymphovascular invasion (yes vs. no, HR = 2.22; p = 0.001) for DMFS, and adjuvant systemic therapy (TKIs vs. TKIs+chemotherapy, HR = 0.42; p = 0.034; TKIs vs. chemotherapy, HR = 0.33; p < 0.001) for DFS. No significant difference was found in the incidence of Grade 3-4 toxicities between groups (p = 0.445).ConclusionsAdjuvant TKIs might be a beneficial choice compared with adjuvant chemotherapy or combination systemic treatments.

Dataset Information

Outcomes of adjuvant epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment for EGFR-mutant non-small-cell lung cancer: a propensity-score analysis.

Publications

Outcomes of adjuvant epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment for EGFR-mutant non-small-cell lung cancer: a propensity-score analysis.

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