A real world analysis of first line treatment of advanced EGFR mutated non-small cell lung cancer: A multi-center, retrospective study

2021 ◽  
pp. 107815522110207
Author(s):  
Chung-Shien Lee ◽  
Iman Ahmed ◽  
Emily Miao ◽  
Shirley Chung ◽  
Khilna Patel ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Retrospective Study ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Front Line ◽  
Small Cell Lung ◽  
Egfr Mutated ◽  
Egfr Tki ◽  
Egfr Tkis

Introduction The recently published FLAURA trial demonstrated that osimertinib has remarkable efficacy in front-line setting for non-small cell lung cancer (NSCLC). While this has transformed current practice, there are no effective treatments following progression on osimertinib. The aim of our study was to compare progression-free survival (PFS) and overall survival (OS) between patients initiated on osimertinib to those started on other EGFR TKIs. Methods This was a multicenter, retrospective study conducted at two large academic centers. Adult patients with EGFR-mutated non-small cell lung cancer (NSCLC) who received EGFR therapy between 2014 and 2019 were included. Patients were dichotomized based on front-line TKI (osimertinib vs. other). PFS, OS, and time-to-discontinuation were evaluated. Results One-hundred seventy-two patients were included in the final analysis. Fifty-two (30.2%) patients received osimertinib and 120 (69.8%) patients received another EGFR TKI. The PFS rates at 6, 12, and 18 months were 86.3%, 79.5%, 69.8% in the osimertinib group and 86.6%, 64.2%, 39.3% in the other EGFR TKI group, respectively (p < 0.0036).Estimated OS at 6, 12, and 18 months was similar for both groups: 94.2%, 94.2%, 80.2% and 95.7%, 93.9%, 84.1%, respectively [Adjusted HR = 0.95 (95% CI, 0.37–2.44; p < 0.9128]. Conclusion Osimertinib demonstrated greater 12 and 18 month PFS compared to other EGFR TKIs. This finding is consistent with results of the FLAURA trial. However, unlike FLAURA, there were no differences in estimated OS between the two groups in our study. Further research to evaluate optimal sequencing strategies in the real world of first, second and third generation TKIs is needed.

scholarly journals Inhibition of β-Catenin Enhances the Anticancer Effect of Irreversible EGFR-TKI in EGFR-Mutated Non–small-cell Lung Cancer with a T790M Mutation

2015 ◽  
Vol 10 (1) ◽  
pp. 93-101 ◽  
Author(s):  
Yosuke Togashi ◽  
Hidetoshi Hayashi ◽  
Masato Terashima ◽  
Marco A de Velasco ◽  
Kazuko Sakai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Anticancer Effect ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Egfr Mutated ◽  
Egfr Tki

ΔCT value of amplified refractory mutation system (ARMS) to predict efficacy of EGFR-TKIs in non-small cell lung cancer: A multicenter retrospective study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20573-e20573
Author(s):  
Laiyu Liu ◽  
Min Chen ◽  
Gong Li ◽  
Dongyong Yang ◽  
Nanjie Xiao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Retrospective Study ◽  
Small Cell Lung Cancer ◽  
Egfr Mutation ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mutation System ◽  
Egfr Mutant ◽  
Egfr Mutated ◽  
Egfr Tkis

e20573 Background: This multi-center retrospective study was to determine whether the ΔCt value of Amplified Refractory Mutation System (ARMS) in EGFR mutated detection in tumors predicts the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small-cell lung cancer (NSCLC). Methods: A total of 108 NSCLC patients harbored an exon 19 deletion (19Del) or exon 21 L858R mutation detected by ARMS were enrolled. We identified patients with ΔCt<1(Group L) harbored a high proportion of EGFR mutation but the patients with ΔCt≥1 (Group H) harbored a low proportion of EGFR mutation in the tumor sample. The progression-free survival (PFS), objective response rates (ORRs) and overall survival (OS) between the groups were analyzed. Results: In the 108 patients we enrolled, 63 were in group L and 45 were in group H. Patients’ demographics and clinical characteristics including age, sex, smoking history, pathology, mutation sites, TNM stage, line of TKIs therapy were not significantly difference between group L and group H. The Median PFS was 331 days (95%CI: 311.8 to 350.2) in group L and 206 days (95%CI, 157.2 to 254.8) in group H and the difference showed statistically significant (P < 0.001). Moreover, the ORRs in group L was significant higher than the group H (60.0% vs 34.9%, P = 0.011). The median OS was 744 days (95%CI, 635.5 to 852.5) in group L and 596 days in group H (95%CI, 491.7 to 700.0) but showed not statistically significant ( P = 0.098). Conclusions: ΔCt value of ARMS in EGFR mutated detection could be an efficacy predictor for EGFR-TKIs treatment in advanced EGFR-mutant NSCLC.

scholarly journals Icotinib is as efficacious as gefitinib for brain metastasis of EGFR mutated non-small-cell lung cancer

2020 ◽  
Author(s):  
Kejun Liu ◽  
Guanming Jiang ◽  
Ailing Zhang ◽  
Zhuanghua Li ◽  
Jun Jia
Keyword(s):  
Lung Cancer ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Significant Difference ◽  
Egfr Mutated ◽  
Egfr Tkis

Abstract Background: The prognosis of non-small-cell lung cancer (NSCLC) with brain metastases is very poor. Currently, therapeutic methods for this patient population include whole-brain radiation therapy (WBRT), surgery, radiosurgery and systemic treatment. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) could be effective on cerebral metastases of mutated NSCLC. However, which EGFR-TKIs is more appropriate is still unknown. Methods: We conducted a retrospective analysis of advanced NSCLC patients with brain metastases for EGFR targeted therapy from November 2013 to April 2018 at Dongguan People’s Hospital, Southern Medical University, China. A total of 43 patients were recruit in this study. Among them, 21 cases received icotinib (125 mg, thrice a day) and 22 cases received gefitinib (250 mg, once a day) until disease progression or unacceptable toxicity. The primary end point of this study was intracranial PFS (iPFS). The relationships between therapeutic arms and patients characteristics were performed using Pearson’s chi-square test or Fisher’s exact test. The differences in PFS among the two arms were analyzed using Kaplan-Meier curves and log rank tests. Results: There was no significant difference of intracranial ORR (66.6% versus 59.1%, P =0.62) and DCR (85.7% versus 81.8%, P =0.73) between the two arms. The median intracranial PFS (iPFS) for icotinib and gefitinib arms were 8.4 months (95% CI, 5.4 to 11.3 months) and 10.6 months (95% CI, 6.3 to 14.8 months), respectively (P =0.17). Adverse events of the two study arms were generally mild. None of the patients experienced dose reduction of EGFR-TKIs. Conclusions: Our study showed that icotinib and gefitinib had similar efficacy for brain metastasis of EGFR mutated NSCLC. Large randomized studies are suggested to further illuminate the effect of these two EGFR-TKIs on cerebral lesions of NSCLC.

scholarly journals ONO-7475, a Novel AXL Inhibitor, Suppresses the Adaptive Resistance to Initial EGFR-TKI Treatment in EGFR-Mutated Non–Small Cell Lung Cancer

2020 ◽  
Vol 26 (9) ◽  
pp. 2244-2256 ◽  
Author(s):  
Naoko Okura ◽  
Naoya Nishioka ◽  
Tadaaki Yamada ◽  
Hirokazu Taniguchi ◽  
Keiko Tanimura ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Adaptive Resistance ◽  
Tki Treatment ◽  
Egfr Mutated ◽  
Egfr Tki

scholarly journals Efficacy of the CDK7 Inhibitor on EMT-Associated Resistance to 3rd Generation EGFR-TKIs in Non-Small Cell Lung Cancer Cell Lines

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2596
Author(s):  
Wonjun Ji ◽  
Yun Jung Choi ◽  
Myoung-Hee Kang ◽  
Ki Jung Sung ◽  
Dong Ha Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Acquired Resistance ◽  
Resistant Cell ◽  
Small Cell ◽  
Small Cell Lung ◽  
Egfr Tki ◽  
Egfr Tkis

Epithelial to mesenchymal transition (EMT) is associated with resistance during EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy. Here, we investigated whether EMT is associated with acquired resistance to 3rd generation EGFR-TKIs, and we explored the effects of cyclin-dependent kinase 7 (CDK7) inhibitors on EMT-mediated EGFR-TKIs resistance in non-small cell lung cancer (NSCLC). We established 3rd generation EGFR-TKI resistant cell lines (H1975/WR and H1975/OR) via repeated exposure to WZ4002 and osimertinib. The two resistant cell lines showed phenotypic changes to a spindle-cell shape, had a reduction of epithelial marker proteins, an induction of vimentin expression, and enhanced cellular mobility. The EMT-related resistant cells had higher sensitivity to THZ1 than the parental cells, although THZ1 treatment did not inhibit EGFR activity. This phenomenon was also observed in TGF-β1 induced EMT cell lines. THZ1 treatment induced G2/M cell cycle arrest and apoptosis in all of the cell lines. In addition, THZ1 treatment led to drug-tolerant, EMT-related resistant cells, and these THZ1-tolerant cells partially recovered their sensitivity to 3rd generation EGFR-TKIs. Taken together, EMT was associated with acquired resistance to 3rd generation EGFR-TKIs, and CDK7 inhibitors could potentially be used as a therapeutic strategy to overcome EMT associated EGFR-TKI resistance in NSCLC.

EGFR-TKI rechallenged treatment combined with apatinib in non-small cell lung cancer with EGFR-TKI resistance.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20529-e20529 ◽  
Author(s):  
Li Liang ◽  
Fang Li ◽  
Baoshan Cao ◽  
Zhaohui Zhang ◽  
Xiang Zhu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Objective Response ◽  
Acquired Resistance ◽  
Small Cell ◽  
Small Cell Lung ◽  
Grade 3 ◽  
Egfr Tki ◽  
Egfr Tkis

e20529 Background: Acquired resistance to EGFR-TKIs frequently occurs in non-small cell lung cancer (NSCLC) patients (pts) with sensitizing EGFR mutations. EGFR-TKIs rechallenged therapy is one of the recommended strategies. This study aimed to explore the efficacy and safety of EGFR-TKI combined with apatinib (a TKI against VEGFR-2) in EGFR-TKIs resistant pts. Methods: From Aug 2015 to Nov 2016, we retrospectively screened 16 NSCLC pts who acquired resistance to the EGFR-TKI therapy and chose apatinib plus EGFR-TKI as the second-line treatment in our hospital. All pts signed informed consent before treatment. Results: Pts characteristics and efficacy are shown in the table below. Two pts discontinued on the 4th and 10th day due to side effects, respectively, and thus were excluded from short efficacy analysis. No CR, 4 PR and 10 SD were confirmed, resulting in an objective response rate of 28.6% and a disease control rate of 100%, respectively. At the cut-off date on Feb 7, 2017, 6 pts were still being treated. The median progression-free survival was 4.60 months (95%CI, 2.23–12.52 months). The main adverse events were hypertension, hand-foot skin reaction (HFSR) and diarrhea. Five (31.3%) grade 3 hypertension, 1 (6.3%) grade 3 HFSR and 1 (6.3%) grade 3 diarrhea were observed. Conclusions: EGFR-TKI combined with apatinib may stand for a new option for NSCLC pts with acquired EGFR-TKIs resistance. [Table: see text]

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