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

Zaarour, Mazen; Weerasinghe, Chanudi; Nazha, Bassel; Hassan, Samer; Atallah, Jean-Paul

doi:10.1586/14737140.2015.1092385

Cited by 11 publications

(5 citation statements)

References 51 publications

(40 reference statements)

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“…This suggests that osimertinib was well tolerated, even in those who potentially had significant comorbidities or who were in generally poorer health, and is consistent with previous studies that have shown that EGFR-TKIs are well tolerated with a mild toxicity profile in elderly patient populations [ 22 , 23 ]. Historically, clinicians have been reluctant to aggressively treat older patients owing to a fear of a greater risk of toxicities [ 24 ], but 50% of patients with NSCLC are aged > 70 years at diagnosis [ 23 ]. Thus, identifying agents, such as osimertinib, that are well tolerated in this population is clinically relevant.…”

Section: Discussionsupporting

confidence: 88%

Osimertinib for Previously Treated Patients With Advanced EGFR T790M Mutation-Positive NSCLC: Tolerability and Diagnostic Methods From an Expanded Access Program

et al. 2018

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Introduction:The osimertinib (AZD9291) US Expanded Access Program (EAP) provided compassionate access to osimertinib prior to US Food and Drug Administration (FDA) approval for patients with advanced/metastatic epidermal growth factor receptor (EGFR) T790M-positive non-small cell lung cancer (NSCLC) following progression on tyrosine kinase inhibitors (TKIs) targeting EGFR. Here, we report the patient demographics, safety and tolerability, and diagnostic methods used for T790M testing in the EAP. Methods: Adult patients with EGFR T790Mpositive NSCLC following progression on prior EGFR-TKI therapy (irrespective of line of therapy) were enrolled in the EAP and treated with 80 mg osimertinib once daily until dose reduction, discontinuation, or completion of the EAP following FDA approval (November 2015). Various testing methods were allowed for the required T790M testing. Results: In total, 248 patients from 25 centers throughout the USA were enrolled in the EAP. The starting dose of 80 mg osimertinib once daily was maintained for 96% (n = 238) of patients over the duration of the EAP (median duration of exposure 84 days). Most patients (overall 83% [n = 205/238]; patients aged C 75 years 83% [n = 48/58]) completed the EAP MyDoanh Chau is also known as Maiyan Chau.Enhanced digital content To view enhanced digital content for this article go to https://doi.org/10.6084/ m9.figshare.6247304.

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Section: Discussionsupporting

confidence: 88%

Osimertinib for Previously Treated Patients With Advanced EGFR T790M Mutation-Positive NSCLC: Tolerability and Diagnostic Methods From an Expanded Access Program

et al. 2018

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“…Regarding racial differences in EGFR mutations, EGFR mutations have been observed in approximately 12%-15% of Caucasian patients with lung adenocarcinoma, but the rate can be as high as 60% in Asian populations 5, 9. For EGFR-TKIs, the most frequently studied drugs are gefitinib and erlotinib 4, 10. Nevertheless, even in patients with EGFR mutations, the treatment efficacy of these drugs is only approximately 60%-70% 11.…”

Section: Introductionmentioning

confidence: 99%

Association between survivin genetic polymorphisms and epidermal growth factor receptor mutation in non-small-cell lung cancer

Liu¹,

Hsieh²,

Wu³

et al. 2016

Int. J. Med. Sci.

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Survivin is an anti-apoptotic protein that is implicated in the regulation of apoptosis and cell cycle in various types of cancers. The current study explored the effect of survivin gene polymorphisms and EGFR mutations in non-small-cell lung carcinoma (NSCLC) patients. A total of 360 participants, including 291 adenocarcinoma lung cancer and 69 squamous cell carcinoma lung cancer patients, were selected for the analysis of three survivin genetic variants (survivin -31, +9194, and +9809) by using real-time PCR genotyping. The results indicated that GC+CC genotypes of survivin -31 were significant association with EGFR mutation in lung adenocarcinoma patients (adjusted odds ratio=3.498, 95% CI = 1.171-10.448; p<0.01). Moreover, The GC+CC genotypes of survivin -31 were associated with EGFR L858R mutation but not in exon 19 in-frame deletions. Furthermore, among patients in exon 19 in-frame deletions, those who have at least one polymorphic G allele of survivin -31 have an increased incidence to develop late-stage when compared with those patients homozygous for C/C (OR, 4.800; 95% CI, 1.305-17.658). In conclusion, our results showed that survivin genetic variants were related to EGFR mutation in lung adenocarcinoma patients and might contribute to pathological development to NSCLC.

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“…Subsequently, we applied an HX103-based FACS assay to analyze the 23 tumor tissues (Supplementary Figs. 26,27). As shown in Fig.…”

Section: Targeting Active-egfr By Hx103 In Cancer Cells With Distinct...mentioning

confidence: 87%

“…The standard method to detect EGFR mutations is based on polymerase chain reaction (PCR) amplified genomic DNA [20][21][22] . Clinical studies have shown that approximately 70-80% (depending on the trials) of EGFR mutation-positive NSCLC patients respond to EGFR-TKI treatment 19,[23][24][25][26][27][28][29][30][31][32] , and a small proportion (~20-30%) of patients carrying EGFR-activating mutations still do not show objective response when treated with EGFR-TKI. This observation suggests that there are probably alternative mechanisms conferring EGFR mutant (in)activation.…”

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confidence: 99%

A fluorogenic probe for predicting treatment response in non-small cell lung cancer with EGFR-activating mutations

et al. 2022

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Therapeutic responses of non-small cell lung cancer (NSCLC) to epidermal growth factor receptor (EGFR) - tyrosine kinase inhibitors (TKIs) are known to be associated with EGFR mutations. However, a proportion of NSCLCs carrying EGFR mutations still progress on EGFR-TKI underlining the imperfect correlation. Structure-function-based approaches have recently been reported to perform better in retrospectively predicting patient outcomes following EGFR-TKI treatment than exon-based method. Here, we develop a multicolor fluorescence-activated cell sorting (FACS) with an EGFR-TKI-based fluorogenic probe (HX103) to profile active-EGFR in tumors. HX103-based FACS shows an overall agreement with gene mutations of 82.6%, sensitivity of 81.8% and specificity of 83.3% for discriminating EGFR-activating mutations from wild-type in surgical specimens from NSCLC patients. We then translate HX103 to the clinical studies for prediction of EGFR-TKI sensitivity. When integrating computed tomography imaging with HX103-based FACS, we find a high correlation between EGFR-TKI therapy response and probe labeling. These studies demonstrate HX103-based FACS provides a high predictive performance for response to EGFR-TKI, suggesting the potential utility of an EGFR-TKI-based probe in precision medicine trials to stratify NSCLC patients for EGFR-TKI treatment.

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

Cited by 11 publications

References 51 publications

Osimertinib for Previously Treated Patients With Advanced EGFR T790M Mutation-Positive NSCLC: Tolerability and Diagnostic Methods From an Expanded Access Program

Osimertinib for Previously Treated Patients With Advanced EGFR T790M Mutation-Positive NSCLC: Tolerability and Diagnostic Methods From an Expanded Access Program

Association between survivin genetic polymorphisms and epidermal growth factor receptor mutation in non-small-cell lung cancer

A fluorogenic probe for predicting treatment response in non-small cell lung cancer with EGFR-activating mutations

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