An Observational Study of Acquired EGFR T790M-Dependent Resistance to EGFR-TKI Treatment in Lung Adenocarcinoma Patients in Taiwan

Wu, Shang Gin; Chiang, Chi‐Lu; Liu, Chien Ying; Wang, Chin Chou; Su, Po‐Lan; Hsia, Te Chun; Shih, Jin‐Yuan; Chang, Gee Chen

doi:10.3389/fonc.2020.01481

Cited by 27 publications

(34 citation statements)

References 40 publications

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“…Wu et al also indicated that the T790M acquisition rate was no difference between patients who received and patients who did not receive chemotherapy before re-biopsy. 30 Furthermore, in the present study, patients with an uncommon EGFR mutation tended to be less likely to develop a T790M mutation (37.0% for exon 19 deletion, 41.3% for L858R, and 0 for uncommon mutation); this finding was consistent with the results of another recent study. 14,31 The cobas test (v2) of circulating cfDNA has been found to detect 61% of tumor specimens with the T790M mutation.…”

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confidence: 93%

The Impact of Acquired EGFR T790M Mutation and EGFR Circulating Cell-Free DNA on Survival in Patients with Lung Adenocarcinoma Following EGFR-TKI Therapy

Cheng

Hsia²,

Tu³

et al. 2021

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confidence: 93%

The Impact of Acquired EGFR T790M Mutation and EGFR Circulating Cell-Free DNA on Survival in Patients with Lung Adenocarcinoma Following EGFR-TKI Therapy

Cheng

Hsia²,

Tu³

et al. 2021

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“…Irrespective of the administration of first‐ or second‐generation EGFR‐TKIs in the first‐line setting, acquired T790M mutation accounts for the majority of resistance mechanisms upon disease progression. Several studies, which mainly conducted in the context of gefitinib or erlotinib resistance, have reported a higher secondary T790M in common mutation than in uncommon one, and the T790M rate in EGFR exon 19 deletion tended to be higher than that in EGFR L858R 25‐27 . However, data of secondary T790M from a pure afatinib‐treated cohort in relation to different EGFR mutation subtypes are limited.…”

Section: Introductionmentioning

confidence: 99%

Afatinib treatment in a large real‐world cohort of nonsmall cell lung cancer patients with common and uncommon epidermal growth factor receptor mutation

Huang

Chiu

et al. 2021

Intl Journal of Cancer

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The epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI) afatinib improves survival in nonsmall cell lung cancer (NSCLC) patients with EGFR mutation. We analysed the outcome between EGFR mutation subtypes in a large afatinib‐treated cohort in which 516 EGFR‐mutated NSCLC patients receiving afatinib as front‐line treatment. EGFR uncommon mutations include exon 20 insertion, de novo T790M of high or low allele frequency (dT790MHAF/dT790MLAF), non‐T790M compound mutation and others, where EGFR exon 20 insertion and dT790MHAF were defined as type‐I and the rest as type‐II uncommon mutation. Four hundred and sixty‐one (89.3%) and 55 (10.7%) patients were common and uncommon mutation, respectively. Exon 20 insertion and dT790MHAF patients demonstrated a significantly shortened progression‐free survival (PFS) (2.6 and 4.1 months) compared to EGFR common mutation, dT790MLAF and other uncommon mutation patients (15.1, 27.0 and 18.4 months; P = 3 × 10−8). Type‐I uncommon mutation was an independent predictor of PFS (HR 4.46 [95% CI, 2.60‐7.64]; P < .001) and OS (HR 2.56 [95% CI, 1.37‐4.75]; P = .003). EGFR L858R patients demonstrated a significantly higher CNS progression (cause‐specific HR, 3.16; 95% CI 1.24‐8.08; P = .016), and type‐I uncommon mutation patients exhibited a significantly higher systemic progression (cause‐specific HR, 4.95; 95% CI 2.30‐10.60; P = 4.3 × 10−5). Tendencies of higher CNS and lower systemic progression were observed in type‐II uncommon mutation patients. A PFS ≥ 12 months (OR 2.38 [95% CI, 1.18‐4.89]; P = .016) and uncommon EGFR mutation (OR 0.08 [95% CI, 0.01‐0.48]; P = .021) were independent predictors of secondary T790M. Afatinib‐treated NSCLC patients presented an EGFR genotype‐specific pattern of disease progression and outcome.

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“…Following approval, the Ministry of Health and Welfare in South Korea granted reimbursement for osimertinib in the 2L setting in December 2017 [23]. In Taiwan, reimbursement for osimertinib in the 2L setting was granted in April 2020 [25]. Testing of tumors for T790M in patients with resistance to 1G/2G EGFR-TKIs in the 1L setting is now mandatory, with osimertinib considered the standard of care for patients with T790M-positive tumors [26].…”

Section: Introductionmentioning

confidence: 99%

Real-world Treatment Patterns in Patients with EGFR Mutation-positive NSCLC Receiving a First-Line, First- or Second-generation EGFR Tyrosine Kinase Inhibitor in South Korea and Taiwan

Lee

Hung

Kim

et al. 2021

Asian Pac J Cancer Biol

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Introduction: The preferred first-line (1L) treatment for epidermal growth factor receptor (EGFR) mutation-positive (EGFRm) advanced/metastatic non-small lung cancer (NSCLC) are EGFR-tyrosine kinase inhibitors (TKIs). However, most patients treated with 1L first- or second-generation (1G/2G) EGFR-TKIs acquire resistance; the EGFR T790M mutation is observed in ~30–50% of patients. We report real-world NSCLC treatment and T790M testing patterns in South Korea and Taiwan. Methods: Retrospective medical record review of EGFRm advanced/metastatic NSCLC patients from routine practice. 1G/2G EGFR-TKI initiation 1 January 2015–31 December 2017 (follow-up end date: last available medical record or August 2019). Study measures: demographic/disease characteristics, 1L/2L treatment, T790M testing. Results: In South Korea, 70% (164/235) and in Taiwan 89% (89/100) experienced 1L disease progression (median [range] follow-up: 22 [2.3–50.7] months). Of those with disease progression, 68% (111/164) and 62% (55/89) had T790M testing in South Korea and Taiwan, respectively. In South Korea, 43% (48/111) were T790M-positive with 88% (n=42/48) receiving osimertinib (mostly 2L). In Taiwan, 18% (10/55) were T790M-positive; 100% received osimertinib. Overall, 73% (120/164) and 63% (63/100) in South Korea and Taiwan, respectively, received 2L therapy, predominantly pemetrexed-containing regimens. Among patients with disease progression, 9% (14/164) and 24% (21/89) died before receiving 2L therapy in South Korea and Taiwan, respectively. Conclusion: In both countries, <70% with 1L disease progression were tested for T790M at any point from NSCLC diagnosis, suggesting resistance mutation testing could be improved. Treatment/testing patterns may have changed in both countries since study initiation due to osimertinib reimbursement changes beginning December 2017.

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An Observational Study of Acquired EGFR T790M-Dependent Resistance to EGFR-TKI Treatment in Lung Adenocarcinoma Patients in Taiwan

Cited by 27 publications

References 40 publications

The Impact of Acquired EGFR T790M Mutation and EGFR Circulating Cell-Free DNA on Survival in Patients with Lung Adenocarcinoma Following EGFR-TKI Therapy

The Impact of Acquired EGFR T790M Mutation and EGFR Circulating Cell-Free DNA on Survival in Patients with Lung Adenocarcinoma Following EGFR-TKI Therapy

Afatinib treatment in a large real‐world cohort of nonsmall cell lung cancer patients with common and uncommon epidermal growth factor receptor mutation

Real-world Treatment Patterns in Patients with EGFR Mutation-positive NSCLC Receiving a First-Line, First- or Second-generation EGFR Tyrosine Kinase Inhibitor in South Korea and Taiwan

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