Common
 EGFR
 -Mutated Subgroups (Del19/L858R) in Advanced Non-Small-Cell Lung Cancer: Chasing Better Outcomes with Tyrosine Kinase Inhibitors

Reguart, Noemı́; Remón, Jordi

doi:10.2217/fon.15.15

Cited by 81 publications

(64 citation statements)

References 67 publications

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“…Approximately 30%–50% of Asian and 10%–17% of Caucasian patients with lung adenocarcinoma harbor activating epidermal growth factor receptor ( EGFR ) mutations 1,2. EGFR-tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib are the preferred treatment for patients with activating EGFR mutations (a deletion in exon 19 [19del] and a point mutation in exon 21 leading to substitution of leucine for arginine at position 858 [L858R]).…”

Section: Introductionmentioning

confidence: 99%

Meta-analysis of the impact of de novo and acquired EGFR T790M mutations on the prognosis of patients with non-small cell lung cancer receiving EGFR-TKIs

Yang¹,

Sun²,

Xiong³

et al. 2017

OTT

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PurposeThe purpose of this meta-analysis was to explore the influences of pretreatment de novo and posttreatment-acquired epidermal growth factor receptor (EGFR) T790M mutations in patients with advanced non-small cell lung cancer (NSCLC) who had received tyrosine kinase inhibitors (TKIs).MethodsWe searched PubMed, Embase, and the China National Knowledge Infrastructure database for eligible literature. Data were extracted to assess the hazard ratios (HRs) for progression-free survival (PFS), overall survival (OS), and post-progression survival (PPS) and the relative ratios (RRs) for objective response rate (ORR).ResultsThis meta-analysis included 22 studies comprising 1,462 patients with NSCLC who harbored activating EGFR mutations and were treated with EGFR-TKIs. Compared to pretreatment T790M mutation-negative NSCLC, pretreatment T790M mutation-positive NSCLC was associated with decreased PFS (HR 2.23, P<0.001) and OS (HR 1.55, P=0.003). A trend toward significance of worsening ORR (RR 0.86, P=0.051) was evident. The acquired T790M mutation was correlated with improved PFS (HR 0.75, P=0.006) and PPS (HR 0.57, P<0.001), compared to patients without the T790M mutation who progressed after EGFR-TKI treatment. There were no significant differences in OS or ORR between patients with acquired T790M mutation-positive and T790M mutation-negative NSCLC. However, in the tumor tissue rebiopsy subgroup, patients with acquired T790M mutation had improved OS (HR 0.60, P<0.001) compared to T790M mutation-negative patients. In the plasma ctDNA subgroup, acquired T790M mutation decreased the OS (HR 1.87, P<0.001).ConclusionPretreatment T790M mutation was associated with worse PFS and OS in patients with advanced NSCLC treated with EGFR-TKIs, while acquired T790M mutation was associated with longer PFS and PPS than T790M mutation-negative NSCLC. The effects on OS were different between acquired T790M mutation detected from rebiopsy of tumor tissue and that detected from plasma ctDNA.

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Section: Introductionmentioning

confidence: 99%

Meta-analysis of the impact of de novo and acquired EGFR T790M mutations on the prognosis of patients with non-small cell lung cancer receiving EGFR-TKIs

Yang¹,

Sun²,

Xiong³

et al. 2017

OTT

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“…Both vary in their activated stability by difference in conformation, and their continuation state of kinase activation after the disruption of dimerization is different also [21]. Reguart et al reported that biological properties of Del19 and L858R mutations differ, with different patterns of EGFR amplification and EGFR autophosphorylation between cell lines containing each mutation [22]. Other experimental reports show that [26].…”

Section: Discussionmentioning

confidence: 99%

Differential efficacy of cisplatin plus pemetrexed between L858R and Del-19 in advanced EGFR-mutant non-squamous non-small cell lung cancer

et al. 2016

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Background: LUX-Lung 3 showed afatinib improved progression-free survival (PFS) compared with cisplatin plus pemetrexed in patients with epidermal growth factor receptor (EGFR) mutations. In this study, chemotherapy efficacy tended to differ between patients with Leu858Arg (L858R) point mutation and Exon 19 deletion (Del-19); PFS in L858R patients (8.1 months) was greater than in Del-19 patients (5.6 months). We investigated whether there is any difference in efficacy of cisplatin plus pemetrexed between Del-19 and L858R.

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“…Somatic EGFR mutations are present in around 50% of patients in Asia and in 10–15% of Caucasian patients with metastatic NSCLC with adenocarcinoma histology (7). Most of these mutations are caused by deletions on the exon 19 or L858R point mutations on exon 21 (8). EGFR-activating mutations lead to aberrant constitutive signaling by EGFR and its associated cell signaling pathways.…”

Section: Introductionmentioning

confidence: 99%

Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Treatment of Metastatic Non-Small Cell Lung Cancer, with a Focus on Afatinib

Abdallah

Hirsh

2017

Front. Oncol.

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Somatic epidermal growth factor receptor (EGFR) mutations are present in around 50% of Asian patients and in 10–15% of Caucasian patients with metastatic non-small cell lung cancer (NSCLC) of adenocarcinoma histology. The first-generation EGFR-tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib have demonstrated improved progression-free survival (PFS) and response rates but not overall survival (OS) benefit in randomized phase III trials when compared with platinum-doublet chemotherapy. All patients treated with EGFR-TKIs will eventually develop acquired resistance to these agents. Afatinib, an irreversible ErbB family blocker, has shown in two randomly controlled trials in patients with EGFR-activating mutations, a significant improvement in PFS and health-related quality of life when compared to platinum-based chemotherapy. Afatinib improved OS in patients with Del19 mutations. In patients having progressed on first-generation EGFR-TKIs, afatinib did lead to a clinical benefit. A randomly controlled trial showed that PFS was significantly superior with afatinib vs. erlotinib in patients with squamous NSCLC in the second-line setting. A phase IIb trial comparing afatinib and gefitinib in first-line EGFR positive NSCLC showed significantly improved PFS with afatinib but OS was not significantly improved.

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Common EGFR -Mutated Subgroups (Del19/L858R) in Advanced Non-Small-Cell Lung Cancer: Chasing Better Outcomes with Tyrosine Kinase Inhibitors

Cited by 81 publications

References 67 publications

Meta-analysis of the impact of de novo and acquired <em>EGFR</em> T790M mutations on the prognosis of patients with non-small cell lung cancer receiving EGFR-TKIs

Meta-analysis of the impact of de novo and acquired <em>EGFR</em> T790M mutations on the prognosis of patients with non-small cell lung cancer receiving EGFR-TKIs

Differential efficacy of cisplatin plus pemetrexed between L858R and Del-19 in advanced EGFR-mutant non-squamous non-small cell lung cancer

Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Treatment of Metastatic Non-Small Cell Lung Cancer, with a Focus on Afatinib

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