Impact of Specific Epidermal Growth Factor Receptor (<i>EGFR</i>) Mutations and Clinical Characteristics on Outcomes After Treatment With EGFR Tyrosine Kinase Inhibitors Versus Chemotherapy in <i>EGFR</i>-Mutant Lung Cancer: A Meta-Analysis

Lee, Chee Khoon; Wu, Yi‐Long; Ding, Pei Ni; Lord, Sarah J.; Inoue, Akira; Zhou, Caicun; Mitsudomi, Tetsuya; Rosell, Rafael; Pavlakis, Nick; Links, Matthew; Gebski, Val; Gralla, Richard J.; Yang, James Chih‐Hsin

doi:10.1200/jco.2014.58.1736

Cited by 281 publications

(217 citation statements)

References 26 publications

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“…It has been reported that NSCLCs with EGFR mutations are associated with better outcomes, whereas KRAS mutations, with worse outcome [28,29]. Moreover, lung cancer of EGFR mutation can be treated with EGFR-TKI and prolong PFS overall than treated with chemotherapy, especially in those with exon 19 deletions, never smokers and women [30]. Our results supported the conclusion that former smokers with NSCLCs may benefit from their specific mutational profiles.…”

Section: Discussionsupporting

confidence: 86%

Former smokers with non‐small‐cell lung cancers: a comprehensive investigation of clinicopathologic characteristics, oncogenic drivers, and prognosis

et al. 2016

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The aim of this present investigation was to evaluate the clinicopathologic characteristics, oncogenic drivers, and prognosis of former smokers with non-smallcell lung cancer (NSCLC), and to compare them with those of the current and never smokers. This investigation was a single-institution retrospective study of 2289 NSCLC patients, who were classified as former, current, or never smokers. A collection was made of the clinicopathological characteristics, spectra of wellidentified driver genes and survival rates. The survival rates were compared using log-rank test, and independent prognostic factors, identified using Cox regression analysis. Of 2289 NSCLC patients, 257 (11.2%) were former smokers; 868 (37.9%), current smokers; and 1164 (50.9%), never smokers. Compared with the current, the former were characterized by older age at diagnosis (64.3y vs. 59.9y; P < 0.001), earlier TNM stage (stage I, 47.9% vs. 39.5%; P = 0.017), fewer solid predominance in adenocarcinomas (16.2% vs. 29.5%; P = 0.005), and more EGFR mutation (33.2% vs. 20.7%; P < 0.001) but less KRAS mutation (6.7% vs. 11.9%, P = 0.041). No statistically significant survival differences were observed between the former and current. However, the light former smokers presented favorable overall survival when compared with the light current and heavy former or current (the light former vs. the heavy former, P = 0.028; the light former vs. the light current, P = 0.048; and the light former vs. the heavy current, P = 0.048). Our findings suggest that the former smokers with NSCLCs can have distinctive clinicopathologic characteristics, oncogenic drivers, and prognosis, and they, especially the light former, can benefit from smoking cessation. Cancer Medicine Open Access 2118

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Section: Discussionsupporting

confidence: 86%

Former smokers with non‐small‐cell lung cancers: a comprehensive investigation of clinicopathologic characteristics, oncogenic drivers, and prognosis

et al. 2016

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“…This finding confirmed the evidence of previous literature supporting a better outcome with first generation TKIs for patients with NSCLC harbouring an exon 19 deletion as EGFR mutation (14,15), suggesting that exon 19 deletion and exon 21 Leu858Arg point mutation define two distinct forms of NSCLC.…”

Section: Tania Losannosupporting

confidence: 91%

“…In this study the authors reported an ORR of 84.6% and a DCR of 96.2%, with a median PFS of 18.0 months. The advantage was reported both for patients with exon 19 deletion positive and patients with Leu858Arg mutationpositive NSCLC, with a tendency to be more effective in tumor with exon 19 deletion, similarly to the results of a recent meta-analysis (15).…”

Section: Tania Losannosupporting

confidence: 80%

A potential new therapeutic option for patients with advanced EGFR mutation-positive non-small cell lung cancer in first-line setting

Gridelli

Losanno

2016

J. Thorac. Dis.

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“…The ORR of EGFR-L858R mutated tumors seems to be slightly lower than 70% with afatinib 40 mg/day, while only at around 50-60% with gefitinib 250 mg/day and intermediate with erlotinib 150 mg/day (7)(8)(9). Indeed, a head-to-head phase II trial (LUX-Lung7) of afatinib 40 mg/day versus gefitinib 250 mg/day showed that the ORRs were 66% vs. 42% and median PFSs of 10.9 vs. 10.8 months (HR 0.71), respectively, for the 133 EGFR-L858R mutated NSCLCs (10 (11,12) and confirmed in all randomized clinical trials of EGFR TKI versus chemotherapy (13). All three-gefitinib, erlotinib and afatinib-Food and Drug Administration (FDA) approved EGFR TKIs continue to be prescribed worldwide without a clear "go-to" drug in view of their different biological doses, toxicities (afatinib with higher rates of mucositis and diarrhea, erlotinib of rash, and gefitinib of liver dysfunction) and provider-patient preferences.…”

mentioning

confidence: 77%

Kinase inhibitor-responsive genotypes in EGFR mutated lung adenocarcinomas: moving past common point mutations or indels into uncommon kinase domain duplications and rearrangements

Costa¹

2016

Transl. Lung Cancer Res.

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Epidermal growth factor receptor (EGFR) mutations were first identified as driver oncogenes in non-small-cell lung cancers (NSCLCs) in 2004 by three separate independent groups (1-3), and originally thought to consistent of only inframe deletions, insertions (i.e., indels) or point mutations within exons 18 to 21 of the kinase domain of EGFR (4). The most abundant EGFR mutations are deletions/indels (around amino-acid residues 747 to 752) of exon 19 (these account for ~45% of all EGFR mutations, with the most common delE746_A750) and the exon 21 point mutation L858R mutation (~35% of all EGFR mutations). Inhibition of mutant EGFR in preclinical models through tyrosine kinase inhibitors (TKIs) unsettles the intracellular signaling cascade, generating cell cycle arrest and apoptosis (5). In the clinic, the 1 st generation EGFR TKIs gefitinib and erlotinib, both reversible ATP mimetics with a favorable therapeutic window in relation to the wild-type (WT) EGFR (4,6), induce overall response rate (ORR), EditorialKinase inhibitor-responsive genotypes in EGFR mutated lung adenocarcinomas: moving past common point mutations or indels into uncommon kinase domain duplications and rearrangements that comprehensive molecular profiling may be necessary to maximize the identification of all cases that can benefit from precision oncology.

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Impact of Specific Epidermal Growth Factor Receptor (EGFR) Mutations and Clinical Characteristics on Outcomes After Treatment With EGFR Tyrosine Kinase Inhibitors Versus Chemotherapy in EGFR-Mutant Lung Cancer: A Meta-Analysis

Cited by 281 publications

References 26 publications

Former smokers with non‐small‐cell lung cancers: a comprehensive investigation of clinicopathologic characteristics, oncogenic drivers, and prognosis

Former smokers with non‐small‐cell lung cancers: a comprehensive investigation of clinicopathologic characteristics, oncogenic drivers, and prognosis

A potential new therapeutic option for patients with advanced EGFR mutation-positive non-small cell lung cancer in first-line setting

Kinase inhibitor-responsive genotypes in EGFR mutated lung adenocarcinomas: moving past common point mutations or indels into uncommon kinase domain duplications and rearrangements

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