Review of EGFRâ€‰TKIs in Metastatic NSCLC, Including Ongoing Trials

Melosky, Barbara

doi:10.3389/fonc.2014.00244

Cited by 57 publications

(47 citation statements)

References 18 publications

(27 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both trials taken alone did not demonstrate a significant improvement in OS. However, a recent combined analysis of LUX-Lung 3 and LUX-Lung 6 showed a survival advantage of 3 months for patients treated with afatinib versus chemotherapy (27.3 vs 24.3 months, HR 0.81, p = 0.037) [17].…”

Section: Second-generation Irreversible Egfr-tkis In the General Popumentioning

confidence: 99%

See 1 more Smart Citation

Epidermal growth factor receptor tyrosine kinase inhibitors in elderly patients with non-small cell lung cancer

Zaarour

Weerasinghe

Nazha

et al. 2015

Expert Review of Anticancer Therapy

View full text Add to dashboard Cite

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. At diagnosis, half of the patients are over 70 years of age, and most present with advanced disease, for which chemotherapy is recommended as first-line treatment. However, the benefit from such therapy is modest and it is at times poorly tolerated. The discovery of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has significantly impacted the treatment of patients with EGFR mutation-positive advanced NSCLC. These novel agents demonstrate efficacy and a favorably mild toxicity profile. Despite limited data in elderly patients, the largest subpopulation in NSCLC, EGFR-TKIs are considered the standard of care therapy for advanced EGFR-positive disease in the elderly. In this review, we seek to compile the available data about the EGFR-TKIs use in elderly patients with advanced NSCLC, with the hope to better understand its role in this major yet, underrepresented, group of patients.

show abstract

Section: Second-generation Irreversible Egfr-tkis In the General Popumentioning

confidence: 99%

“…This results in EGFR deactivation, and subsequently deactivation of the downstream signaling networks [17]. The first available EGFR-TKIs were gefitinib and erlotinib, two orally active inhibitors.…”

Section: First-generation Reversible Egfr-tkis: Gefitinib and Erlotinibmentioning

confidence: 99%

Epidermal growth factor receptor tyrosine kinase inhibitors in elderly patients with non-small cell lung cancer

Zaarour

Weerasinghe

Nazha

et al. 2015

Expert Review of Anticancer Therapy

View full text Add to dashboard Cite

show abstract

“…Erlotinib is a potent first-generation inhibitor of EGFR, and is an established first-line therapy for patients with NSCLC positive for exon 19 deletions or exon 21 mutations (1). Erlotinib blocks EGFR kinase activity, suppressing downstream signaling via multiple intermediates including the MAPK and PI3K–AKT pathways (2).…”

Section: Introductionmentioning

confidence: 99%

Phase I Dose-Escalation Study of Linsitinib (OSI-906) and Erlotinib in Patients with Advanced Solid Tumors

Macaulay

Middleton

Eckhardt

et al. 2016

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose Cross-talk between type I IGF receptor (IGF1R), insulin receptor (INSR), and epidermal growth factor receptor (EGFR) mediates resistance to individual receptor blockade. This study aimed to determine the MTD, safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of linsitinib, a potent oral IGF1R/INSR inhibitor, with EGFR inhibitor erlotinib. Experimental Design This open-label, dose-escalation study investigated linsitinib schedules S1: once daily intermittent (days 1–3 weekly); S2, once daily continuous; S3, twice-daily continuous; each with erlotinib 100–150 mg once daily; and a non–small cell lung cancer (NSCLC) expansion cohort. Results Ninety-five patients were enrolled (S1, 44; S2, 24; S3, 12; expansion cohort, 15) and 91 treated. Seven experienced dose-limiting toxicities: QTc prolongation (3), abnormal liver function (2), hyperglycemia (1), and anorexia (1). Common adverse events included drug eruption (84%), diarrhea (73%), fatigue (68%), nausea (58%), vomiting (40%). MTDs for linsitinib/erlotinib were 450/150 mg (S1), 400/100 mg (S2). On the basis of prior monotherapy data, S3 dosing at 150 mg twice daily/150 mg once daily was the recommended phase II dose for the expansion cohort. There was no evidence of drug–drug interaction. Pharmacodynamic data showed IGF-1 elevation and reduced IGF1R/INSR phosphorylation, suggesting pathway inhibition. Across schedules, 5/75 (7%) evaluable patients experienced partial responses: spinal chordoma (268+ weeks), rectal cancer (36 weeks), three NSCLCs including 2 adenocarcinomas (16, 72 weeks), 1 squamous wild-type EGFR NSCLC (36 weeks). Disease control (CR+PR+SD) occurred in 38 of 75 (51%), and 28 of 91 (31%) patients were on study >12 weeks. Conclusions The linsitinib/erlotinib combination was tolerable with preliminary evidence of activity, including durable responses in cases unlikely to respond to erlotinib monotherapy.

show abstract

“…For NSCLC patients whose tumors test positive for any EGFR mutations, an oral tyrosine kinase inhibitor (TKI) is now the preferred first-line therapy. However, only 10-30 % of NSCLC patients have an EGFR gene mutation [6]. Thus, the development of new effective therapeutic targets to approach lung cancer is extremely necessary.…”

Section: Introductionmentioning

confidence: 99%

Knockdown of eIF3d inhibits cell proliferation through G2/M phase arrest in non-small cell lung cancer

2015

View full text Add to dashboard Cite

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and remains the leading cause of cancer-related death worldwide. Eukaryotic translation initiation factor 3, subunit d (eIF3d) has been recognized recently in several human cancers. In this paper, we attempt to evaluate the functional role of eIF3d in NSCLC cells. Lentivirus-mediated RNA interference (RNAi) was applied to silence eIF3d in the human NSCLC cell lines A549 and 95D. Cell viability was measured by MTT. Cell colony-forming ability was measured by colony formation. Cell cycle progression was determined by propidium iodide staining and flow cytometry. Intracellular signaling molecules were detected using a PathScan(®) intracellular signaling array kit. In this study, we firstly proved that lentivirus-mediated RNAi specifically suppressed the expression of eIF3d both at the mRNA and protein levels in A549 and 95D cell lines. Further investigations revealed that eIF3d knockdown significantly inhibited cell proliferation and colony formation. Moreover, the cell cycle of A549 cells was arrested at G2/M phase after eIF3d knockdown. Furthermore, the activations of AKT, HSP27 and SAPK/JNK were suppressed by eIF3d knockdown. This study highlights the crucial role of eIF3d in promoting NSCLC cell proliferation, and provides a foundation for further study into the clinical potential of lentiviral-mediated delivery of eIF3d RNAi therapy for treatment of NSCLC.

show abstract

Review of EGFRâ€‰TKIs in Metastatic NSCLC, Including Ongoing Trials

Cited by 57 publications

References 18 publications

Epidermal growth factor receptor tyrosine kinase inhibitors in elderly patients with non-small cell lung cancer

Epidermal growth factor receptor tyrosine kinase inhibitors in elderly patients with non-small cell lung cancer

Phase I Dose-Escalation Study of Linsitinib (OSI-906) and Erlotinib in Patients with Advanced Solid Tumors

Knockdown of eIF3d inhibits cell proliferation through G2/M phase arrest in non-small cell lung cancer

Contact Info

Product

Resources

About