Outcomes in patients with non-small-cell lung cancer and acquired Thr790Met mutation treated with osimertinib: a genomic study

Lin, Chia‐Chi; Shih, Jin‐Yuan; Yu, Chong‐Jen; Ho, Chao‐Chi; Lee, Jih-Hsing; Tsai, Tzu‐Hsiu; Su, Kang-Yi; Hsieh, Min‐Shu; Chang, Yih‐Leong; Bai, Ya-Ying; Huang, Derek De-Rui; Thress, Kenneth S.; Yang, James Chih‐Hsin

doi:10.1016/s2213-2600(17)30480-0

Cited by 128 publications

(142 citation statements)

References 22 publications

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“…NGS, the results for which are usually expressed as allele frequency, has the potential to become widely adopted for liquid biopsy analysis because it is able to simultaneously identify various genetic alterations including those responsible for resistance to targeted therapy. [24][25][26][27][28][29][30][31] Our findings suggest that the monitoring of allele frequency for EGFRactivating mutations in cfDNA by NGS may also be useful for the prediction of EGFR-TKI treatment efficacy.…”

Section: Discussionmentioning

confidence: 76%

“…Such a pattern was also evident for the allele frequency of EGFR ‐activating mutations (the ratio of the number of activating mutations to the total number of EGFR alleles) as determined by ddPCR (data not shown). NGS, the results for which are usually expressed as allele frequency, has the potential to become widely adopted for liquid biopsy analysis because it is able to simultaneously identify various genetic alterations including those responsible for resistance to targeted therapy . Our findings suggest that the monitoring of allele frequency for EGFR ‐activating mutations in cfDNA by NGS may also be useful for the prediction of EGFR‐TKI treatment efficacy.…”

Section: Discussionmentioning

confidence: 83%

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Longitudinal monitoring of somatic genetic alterations in circulating cell‐free DNA during treatment with epidermal growth factor receptor–tyrosine kinase inhibitors

Iwama

Sakai

Hidaka

et al. 2019

Cancer

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Background The aim of this study was to evaluate the potential of liquid biopsy for prediction of the efficacy of epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitor (TKI) treatment and for assessment of the changes in genetic alterations during such treatment. Methods Plasma samples were prospectively collected from non–small cell lung cancer patients with EGFR‐activating mutations during EGFR‐TKI treatment until disease progression and were analyzed for such mutations with droplet digital polymerase chain reaction and for other somatic alterations with next‐generation sequencing. Results One hundred patients, including 87 who were EGFR‐TKI naïve, were enrolled. Median progression‐free survival was significantly shorter for EGFR‐TKI–naïve patients with EGFR‐activating mutations detected in plasma at baseline than for those without them (7.9 vs 19.0 months; P < .001), with the values being significantly longer for initially positive patients who became negative for these mutations at 12 or 24 weeks than for those who remained positive. An increase in the number of alleles positive for EGFR‐activating mutations in plasma during treatment was associated with disease progression, with a hazard ratio of 4.72 (95% CI, 2.07‐10.79; P < .001) for EGFR‐TKI–naïve patients showing an increase within 36 weeks. For 55 patients with available samples, the total number of somatic alterations (other than activating mutations or T790M of EGFR) in plasma was higher at disease progression than at baseline (33 vs 19; P = 0.04). Conclusion Liquid biopsy shows potential for prediction of EGFR‐TKI efficacy and elucidation of clonal tumor evolution during targeted therapy.

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 83%

Longitudinal monitoring of somatic genetic alterations in circulating cell‐free DNA during treatment with epidermal growth factor receptor–tyrosine kinase inhibitors

Iwama

Sakai

Hidaka

et al. 2019

Cancer

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“…This is underpinned by concerns on the potential impact of selective pressures imposed by 3G TKI, best revealed by emerging understanding of resistance mechanisms. Multiple studies have attempted to characterize resistance to osimertinib, with a range of different mechanisms described to date [16][17][18][19][20]. These include EGFR dependent mechanisms and non-canonical mechanisms such as alternative bypass pathway activation and histological changes.…”

Section: Should All Patients Receive Upfront 3 Rd Generation Egfr Tki?mentioning

confidence: 99%

Third generation EGFR TKI landscape for metastatic EGFR mutant non-small cell lung cancer (NSCLC)

Tan

Teh

Lai

et al. 2019

Expert Review of Anticancer Therapy

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“…However, some patients develop drug resistance after using EGFR‐TKI drugs. In most cases, this is due to a point mutation in position 790 of EGFR 20 exon, one of the most recognized drug resistance mechanisms . There are two manifestations of drug resistance in clinical practice, slow progression and explosive progression.…”

Section: Introductionmentioning

confidence: 99%

“…In most cases, this is due to a point mutation in position 790 of EGFR 20 exon, one of the most recognized drug resistance mechanisms. 4 There are two manifestations of drug resistance in clinical practice, slow progression and explosive progression. According to the response evaluation criteria in solid tumors (RECIST) 1.1 tumor staging criteria, the clinical manifestation of patients with slow progression is between stable disease (SD) and progressive disease (PD).…”

Section: Introductionmentioning

confidence: 99%

Clinical study of apatinib combined with EGFR‐TKI in the treatment of chronic progression after EGFR‐TKI treatment in non‐small cell lung cancer (ChiCTR1800019185)

Liu

Zhang

et al. 2020

Thoracic Cancer

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This clinical trial (ChiCTR1800019185) is designed to be an open‐label, prospective, single‐center, single arm exploratory research study. The study will recruit non‐small cell lung cancer patients (NSCLC) with slow progression after first‐line treatment with EGFR‐TKI drugs. Slow progression will be confirmed by the presence of serum carcinoembryonic antigen or imaging evaluation. The primary aim is to assess progression‐free survival after EGFR‐TKIs treatment combined with apatinib 250 mg once daily. The secondary objectives are to evaluate objective efficacy, disease control rates, quality of life, overall survival, and safety. From September 2018 to September 2020, under specific entry and discharge standards, we plan to enroll 38 eligible patients until the end of the study. We hope that our study will help to explore a new way of combining the small molecular inhibitors of antiangiogenesis with EGFR‐TKIs to overcome acquired drug resistance.

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Outcomes in patients with non-small-cell lung cancer and acquired Thr790Met mutation treated with osimertinib: a genomic study

Cited by 128 publications

References 22 publications

Longitudinal monitoring of somatic genetic alterations in circulating cell‐free DNA during treatment with epidermal growth factor receptor–tyrosine kinase inhibitors

Longitudinal monitoring of somatic genetic alterations in circulating cell‐free DNA during treatment with epidermal growth factor receptor–tyrosine kinase inhibitors

Third generation EGFR TKI landscape for metastatic EGFR mutant non-small cell lung cancer (NSCLC)

Clinical study of apatinib combined with EGFR‐TKI in the treatment of chronic progression after EGFR‐TKI treatment in non‐small cell lung cancer (ChiCTR1800019185)

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