Association of EGFR Tyrosine Kinase Inhibitor Treatment With Progression-Free Survival Among Taiwanese Patients With Advanced Lung Adenocarcinoma and EGFR Mutation

Chen, Po‐Yen; Wang, Chin‐Chou; Hsu, Chien‐Ning

doi:10.3389/fphar.2021.720687

Cited by 4 publications

(11 citation statements)

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“…Using the Taiwanese National Health Insurance Research Database (NHIRD) and National Cancer Registry, in this retrospective cohort study we identified patients with newly diagnosed NSCLC from 2011 to 2018. According to the insurance regulation in Taiwan, the first-line TKIs were only reimbursed for advanced (stage IIIb, IIIc, or IV) lung adenocarcinoma harboring EGFR sequence variation, and restricted for monotherapy . The cancer stage recorded by National Cancer Registry was the date of the diagnosis of NSCLC.…”

Section: Methodsmentioning

confidence: 99%

Assessment of Tyrosine Kinase Inhibitors and Survival and Cardiovascular Outcomes of Patients With Non–Small Cell Lung Cancer in Taiwan

et al. 2023

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ImportanceTyrosine kinase inhibitors (TKIs) have been recognized as the standard treatment for patients with non–small cell lung cancers (NSCLCs) and epidermal growth factor receptor (EGFR) sequence variation. Although TKIs have been reported to cause cardiotoxicity, they are widely administered owing to the high prevalence of EGFR sequence variation in Taiwan.ObjectiveTo compare the outcomes of death and major adverse cardiac and cerebrovascular events among patients with NSCLC who use and do not use TKIs in a national cohort.Design, Setting, and ParticipantsUsing data from the Taiwanese National Health Insurance Research Database and National Cancer Registry, patients treated for NSCLC from 2011 to 2018 were identified, and their outcomes were analyzed, including death and major adverse cardiac and cerebrovascular events (MACCEs; such as heart failure, acute myocardial infarction, and ischemic stroke) after adjusting for age, sex, cancer stage, comorbidities, anticancer therapies, and cardiovascular drugs. The median follow-up duration was 1.45 years. The analyses were performed from September 2022 to March 2023.ExposuresTKIs.Main Outcomes and MeasuresCox proportional hazards models were used to estimate death and MACCEs in patients treated with and without TKIs. Given that death may reduce the incidence of cardiovascular events, the competing risk method was used to calculate the MACCE risk after adjustment for all potential confounders.ResultsOverall, 24 129 patients treated with TKIs were matched with 24 129 patients who did not receive TKIs (24 215 [50.18%] were female; and the mean [SD] age was 66.93 [12.37] years). Compared with those not receiving TKIs, the TKI group presented with a significantly lower hazard ratio (HR) of all-cause death (adjusted HR, 0.76; 95% CI, 0.75-0.78; P &lt; .001), and the reason for death was primarily cancer. In contrast, the HR of MACCEs significantly increased (subdistribution HR, 1.22; 95% CI, 1.16-1.29; P &lt; .001) in the TKI group. Furthermore, afatinib use was associated with a significantly reduced risk of death among patients receiving various TKIs (adjusted HR, 0.90; 95% CI, 0.85-0.94; P &lt; .001) compared with those receiving erlotinib and gefitinib, although the outcomes of MACCEs were similar between the 2 groups.Conclusions and RelevanceIn this cohort study of patients with NSCLC, TKI use was associated with reduced HRs of cancer-related death but increased HRs of MACCEs. These findings suggest the importance of close monitoring of cardiovascular problems in individuals receiving TKIs.

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Section: Methodsmentioning

confidence: 99%

Assessment of Tyrosine Kinase Inhibitors and Survival and Cardiovascular Outcomes of Patients With Non–Small Cell Lung Cancer in Taiwan

et al. 2023

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“…Previous reports showed that afatinib as a first-line treatment provided better survival outcomes for advanced EGFR-mutant lung adenocarcinoma than gefitinib and erlotinib [32][33][34]. Afatinib is also effective for pulmonary adenocarcinomas with complex EGFR mutations, especially those with uncommon mutations [33]. Erlotinib and afatinib revealed better treatment efficacy in patients with initial brain metastases than gefitinib [33].…”

Section: Egfrmentioning

confidence: 98%

“…Therefore, many patients still received secondgeneration EGFR-TKIs, including afatinib, as the first-line treatment [1]. Previous reports showed that afatinib as a first-line treatment provided better survival outcomes for advanced EGFR-mutant lung adenocarcinoma than gefitinib and erlotinib [32][33][34]. Afatinib is also effective for pulmonary adenocarcinomas with complex EGFR mutations, especially those with uncommon mutations [33].…”

Section: Egfrmentioning

confidence: 99%

“…Afatinib is also effective for pulmonary adenocarcinomas with complex EGFR mutations, especially those with uncommon mutations [33]. Erlotinib and afatinib revealed better treatment efficacy in patients with initial brain metastases than gefitinib [33]. In a retrospective study, alternative treatment with Chinese herbal medicine (CHM) during first-line EGFR-TKI showed a tolerable toxicity profile and a tendency toward better progression-free sur-vival (PFS)and overall survival (OS) than those who did not receive CHM [35].…”

Section: Egfrmentioning

confidence: 99%

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State-of-the-Art Molecular Oncology of Lung Cancer in Taiwan

Luo

Liang²,

Huang³

et al. 2022

IJMS

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Lung cancers are life-threatening malignancies that cause great healthcare burdens in Taiwan and worldwide. The 5-year survival rate for Taiwanese patients with lung cancer is approximately 29%, an unsatisfactorily low number that remains to be improved. We first reviewed the molecular epidemiology derived from a deep proteogenomic resource in Taiwan. The nuclear factor erythroid 2-related factor 2 (NRF2)antioxidant mechanism was discovered to mediate the oncogenesis and tumor progression of lung adenocarcinoma. Additionally, DNA replication, glycolysis and stress response are positively associated with tumor stages, while cell-to-cell communication, signaling, integrin, G protein coupled receptors, ion channels and adaptive immunity are negatively associated with tumor stages. Three patient subgroups were discovered based on the clustering analysis of protein abundance in tumors. The first subgroup is associated with more advanced cancer stages and visceral pleural invasion, as well as higher mutation burdens. The second subgroup is associated with EGFR L858R mutations. The third subgroup is associated with PI3K/AKT pathways and cell cycles. Both EGFR and PI3K/AKT signaling pathways have been shown to induce NRF2 activation and tumor cell proliferation. We also reviewed the clinical evidence of patient outcomes in Taiwan given various approved targeted therapies, such as EGFR-tyrosine kinase inhibitors and anaplastic lymphoma kinase (ALK)inhibitors, in accordance with the patients’ characteristics. Somatic mutations occurred in EGFR, KRAS, HER2 and BRAF genes, and these mutations have been detected in 55.7%, 5.2%, 2.0% and 0.7% patients, respectively. The EGFR mutation is the most prevalent targetable mutation in Taiwan. EML4-ALK translocations have been found in 9.8% of patients with wild-type EGFR. The molecular profiling of advanced NSCLC is critical to optimal therapeutic decision-making. The patient characteristics, such as mutation profiles, protein expression profiles, drug-resistance profiles, molecular oncogenic mechanisms and patient subgroup systems together offer new strategies for personalized treatments and patient care.

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“…This online search was supplemented by manual searches of the reference lists of eligible studies. [16][17][18][19][20][21][22][23][24][25][26]…”

Section: Information Sources and Search Strategymentioning

confidence: 99%

Do patient characteristics affect EGFR tyrosine kinase inhibitor treatment outcomes? A network meta‐analysis of real‐world survival outcomes of East Asian patients with advanced non‐small cell lung cancer treated with first‐line EGFR‐TKIs

Chang,

Wang,

Tseng

et al. 2023

Thoracic Cancer

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BackgroundDespite the well‐established efficacies of tyrosine kinase inhibitors (TKIs) in epidermal growth factor receptor (EGFR)‐mutated non‐small cell lung cancer (NSCLC), there is limited real‐world evidence comparing their effectiveness according to patients’ clinical characteristics. This network meta‐analysis (NMA) compared survival outcomes among first‐line EGFR‐TKIs in different subgroups of East Asian patients with advanced NSCLC.MethodsThis NMA included real‐world observational studies reporting outcomes with TKIs in patients aged >65 years, with baseline brain metastasis, with different Eastern Cooperative Oncology Group (ECOG) statuses, or with different common EGFR mutation types.ResultsIn patients with the EGFR L858R mutation, afatinib resulted in significantly longer progression‐free survival (PFS) than erlotinib (hazard ratio [HR]: 0.59, 95% confidence interval [CI]: 0.46–0.75) and gefitinib (HR: 0.41, 95% CI: 0.32–0.53). Similarly, in patients with the EGFR Del19 mutation, afatinib and erlotinib resulted in significantly longer PFS than gefitinib (HR: 0.48 with 95% CI: 0.33–0.71 and HR: 0.54 with 95% CI: 0.36–0.80, respectively). Moreover, afatinib resulted in significantly longer PFS than gefitinib in patients with brain metastasis (HR: 0.53, 95% CI: 0.33–0.87) or ECOG status 0–1 (HR: 0.37, 95% CI: 0.23–0.59).ConclusionThis NMA suggests that afatinib results in similar PFS to erlotinib and superior PFS than gefitinib in patients with Del19 mutant NSCLC, aged ≥65 years, with ECOG scores of 0–1, and with baseline brain metastasis.

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Association of EGFR Tyrosine Kinase Inhibitor Treatment With Progression-Free Survival Among Taiwanese Patients With Advanced Lung Adenocarcinoma and EGFR Mutation

Cited by 4 publications

References 34 publications

Assessment of Tyrosine Kinase Inhibitors and Survival and Cardiovascular Outcomes of Patients With Non–Small Cell Lung Cancer in Taiwan

Assessment of Tyrosine Kinase Inhibitors and Survival and Cardiovascular Outcomes of Patients With Non–Small Cell Lung Cancer in Taiwan

State-of-the-Art Molecular Oncology of Lung Cancer in Taiwan

Do patient characteristics affect EGFR tyrosine kinase inhibitor treatment outcomes? A network meta‐analysis of real‐world survival outcomes of East Asian patients with advanced non‐small cell lung cancer treated with first‐line EGFR‐TKIs

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