The Combination of Afatinib and Bevacizumab in Untreated EGFR-Mutated Advanced Lung Adenocarcinoma: A Multicenter Observational Study

Hsu, Ping‐Chih; Huang, Ching Feng; Wang, Chin‐Chou; Kuo, Scott Chih‐Hsi; Chu, Chia-Hsun; Tung, Pi-Hung; Huang, Allen Chung-Cheng; Wang, Chih‐Liang; Chiu, Li-Chung; Fang, Yueh‐Fu; Yang, Cheng‐Ta

doi:10.3390/ph13110331

Cited by 14 publications

(30 citation statements)

References 38 publications

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“…Fourteen (51.8%) of them received re-biopsy, and 8 (57%) patients harbored T790M mutation. Previous clinical trials and real-world data have also confirmed that the combination treatment of EGFR-TKI and anti-angiogenic agents did not influence the frequency of T790M mutation [16,19,21]. In a FLAURA study, NSCLC patients harboring OS than patients with first-generation EGFR-TKIs [8,9].…”

Section: Discussionmentioning

confidence: 86%

The Clinical Outcomes of Different First-Line EGFR-TKIs Plus Bevacizumab in Advanced EGFR-Mutant Lung Adenocarcinoma

et al. 2022

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The aim of this study was to investigate the efficacy of various Epidermal Growth Factor Receptor (EGFR)-Tyrosine Kinase Inhibitors (TKIs) plus bevacizumab in advanced EGFRmutant lung adenocarcinoma patients. Materials and MethodsFrom August 2016 to October 2020, we enrolled advanced lung adenocarcinoma patients harboring exon 19 deletion or L858R receiving gefitinib, erlotinib and afatinib plus bevacizumab as the first-line treatment for the purposes of analysis. ResultsA total of 36 patients were included in the final analysis. Three patients received gefitinib, 17 received erlotinib, and 16 received afatinib combined with bevacizumab as the first-line treatment. The objective response rate was 77.8%, and disease control rate was 94.4%. The overall median progression-free survival (PFS) was 16.4 months, while the median PFS was 17.1 months in patients with exon 19 deletion, and 16.2 months in patients with L858R mutation (p=0.311). Regarding the use of different EGFR-TKIs, the median PFS was 17.1 months in the erlotinib group and 21.6 months in the afatinib group (p=0.617). In patients with brain metastasis at baseline, the median PFS was 18.9 months in the erlotinib group and 16.4 months in the afatinib group (p=0.747). Amongst patients harboring exon 19 deletion, the median PFS was 16.2 months in the erlotinib group and not-reached in the afatinib group (p=0.141). In patients with L858R mutation, the median PFS was 18.9 months in the erlotinib group and 16.2 months in the afatinib group (p=0.481). ConclusionOur research demonstrates that not only erlotinib combined with bevacizumab, but also afatinib CANCER RESEARCH AND TREATMENT (CRT) 4

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Section: Discussionmentioning

confidence: 86%

The Clinical Outcomes of Different First-Line EGFR-TKIs Plus Bevacizumab in Advanced EGFR-Mutant Lung Adenocarcinoma

et al. 2022

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“…The OS analysis of our study showed that exon 19 deletion mutation patients tended to have longer OS than those with the L858R mutation. In the final OS analysis of the NEJ026 trial, patients who received osimertinib as second-line therapy had longer survival than those receiving chemotherapy (50.7 months vs. 40.1 months) [ 39 ]. Together, these findings may explain why the OS of patients with the exon 19 deletion mutation was longer than that of patients with the L858R mutation in our study.…”

Section: Discussionmentioning

confidence: 99%

A Real-World Analysis of Patients with Untreated Metastatic Epidermal Growth Factor Receptor (EGFR)-Mutated Lung Adenocarcinoma Receiving First-Line Erlotinib and Bevacizumab Combination Therapy

et al. 2021

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Introduction: The clinical features of patients with metastatic epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma receiving first-line therapy based on erlotinib combined with bevacizumab are unclear. Here, we sought to analyze the clinical features of this patient group. Methods: Data were analyzed for the period from January 2015 to August 2019 for 49 patients with metastatic EGFR-mutated lung adenocarcinoma receiving first-line erlotiniband-bevacizumab combination therapy from the Linkou and Kaohsiung Chang Gung Memorial Hospitals. Results: The combination of erlotinib and bevacizumab showed an 83.7% objective response rate and a 97.9% disease control rate. The median progression-free survival (PFS) and overall survival (OS) were 22.0 [95% CI (19.7-22.33)] and 47.6 [95% CI (38.87-56.37)] months, respectively, for all patients. The secondary EGFR-T790M mutation rate in the patients with acquired resistance to the combination was 72.4%. No predictive factor associated with the appearance of secondary EGFR-T790M mutations was found. The most frequent adverse event (AE) caused by the combination therapy was dermatitis (100%), and most of the AEs were manageable and grades 1 and 2. Conclusion: Erlotinib combined with bevacizumab is an effective and safe therapy for untreated metastatic EGFR-mutated lung adenocarcinoma. The combination does not alter secondary EGFR-T790M mutations in patients with acquired resistance and is feasible in realworld clinical practice.

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“…Currently, the combination of TKI and antiangiogenic agents for NSCLC patients with EGFR mutation would prolong the progression-free survival (PFS) compared to treating TKI alone group [240][241][242][243][244]. FAK takes part in angiogenesis.…”

Section: Fak Inhibitors In Combination Regimesmentioning

confidence: 99%

FAK in Cancer: From Mechanisms to Therapeutic Strategies

Chuang

Zhen

Tsai

et al. 2022

IJMS

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Focal adhesion kinase (FAK), a non-receptor tyrosine kinase, is overexpressed and activated in many cancer types. FAK regulates diverse cellular processes, including growth factor signaling, cell cycle progression, cell survival, cell motility, angiogenesis, and the establishment of immunosuppressive tumor microenvironments through kinase-dependent and kinase-independent scaffolding functions in the cytoplasm and nucleus. Mounting evidence has indicated that targeting FAK, either alone or in combination with other agents, may represent a promising therapeutic strategy for various cancers. In this review, we summarize the mechanisms underlying FAK-mediated signaling networks during tumor development. We also summarize the recent progress of FAK-targeted small-molecule compounds for anticancer activity from preclinical and clinical evidence.

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The Combination of Afatinib and Bevacizumab in Untreated EGFR-Mutated Advanced Lung Adenocarcinoma: A Multicenter Observational Study

Cited by 14 publications

References 38 publications

The Clinical Outcomes of Different First-Line EGFR-TKIs Plus Bevacizumab in Advanced EGFR-Mutant Lung Adenocarcinoma

The Clinical Outcomes of Different First-Line EGFR-TKIs Plus Bevacizumab in Advanced EGFR-Mutant Lung Adenocarcinoma

A Real-World Analysis of Patients with Untreated Metastatic Epidermal Growth Factor Receptor (EGFR)-Mutated Lung Adenocarcinoma Receiving First-Line Erlotinib and Bevacizumab Combination Therapy

FAK in Cancer: From Mechanisms to Therapeutic Strategies

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