MA04.05 P53 Non-Disruptive Mutation is a Negative Predictive Factor for OS and PFS in EGFR M+ NSCLC Treated with TKI

Roeper, J.; Netchaeva, Maria; Lueers, Anne Christina; Prenzel, R; Sriba, Douglas; Willborn, K.; Stropiep, Ursula; Hallas, Cora; Tiemann, Markus; Neemann, Nicole; Heukamp, Lukas C.; Griesinger, Frank; Falk, Markus

doi:10.1016/j.jtho.2016.11.400

Cited by 2 publications

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“…We could not confirm the correlation between TP53 mutation and shorter PFS that has been reported by different preliminary studies [10,16,17,18,19,33]. The frequency of TP53 mutations was only 17.3% in our cohort whereas it ranged between 30.1% and 62% in the above mentioned reports.…”

Section: Discussioncontrasting

confidence: 97%

“…In addition, patients carrying somatic mutations in the PI3K/AKT/mTOR pathway had a shorter PFS and overall survival (OS) when compared to patients without mutations. Finally, different studies have suggested that mutations in TP53 are associated with shorter PFS in EGFR mutant NSCLC patients receiving treatment with EGFR TKIs [7,13,14,15,16,17].…”

Section: Introductionmentioning

confidence: 99%

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The Presence of Concomitant Mutations Affects the Activity of EGFR Tyrosine Kinase Inhibitors in EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC) Patients

Rachiglio

Fenizia

Piccirillo

et al. 2019

Cancers

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Recent findings suggest that a fraction of EGFR-mutant non-small-cell lung cancers (NSCLC) carry additional driver mutations that could potentially affect the activity of EGFR tyrosine kinase inhibitors (TKIs). We investigated the role of concomitant KRAS, NRAS, BRAF, PIK3CA, MET and ERBB2 mutations (other mutations) on the outcome of 133 EGFR mutant patients, who received first-line therapy with EGFR TKIs between June 2008 and December 2014. Analysis of genomic DNA by Next Generation Sequencing (NGS) revealed the presence of hotspot mutations in genes other than the EGFR, including KRAS, NRAS, BRAF, ERBB2, PIK3CA, or MET, in 29/133 cases (21.8%). A p.T790M mutation was found in 9/133 tumour samples (6.8%). The progression free survival (PFS) of patients without other mutations was 11.3 months vs. 7 months in patients with other mutations (log-rank test univariate: p = 0.047). In a multivariate Cox regression model including the presence of other mutations, age, performance status, smoking status, and the presence of p.T790M mutations, the presence of other mutations was the only factor significantly associated with PFS (Hazard Ratio 1.63, 95% CI 1.04–2.58; p = 0.035). In contrast, no correlation was found between TP53 mutations and patients’ outcome. These data suggest that a subgroup of EGFR mutant tumours have concomitant driver mutations that might affect the activity of first-line EGFR TKIs.

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Section: Discussioncontrasting

confidence: 97%

Section: Introductionmentioning

confidence: 99%

The Presence of Concomitant Mutations Affects the Activity of EGFR Tyrosine Kinase Inhibitors in EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC) Patients

Rachiglio

Fenizia

Piccirillo

et al. 2019

Cancers

View full text Add to dashboard Cite

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Prospective exosome‐focused translational research for afatinib study of non‐small cell lung cancer patients expressing EGFR (EXTRA study)

et al. 2018

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Patients with EGFR‐mutated non‐small cell lung cancer (NSCLC) exhibit resistance to EGFR‐tyrosine kinase inhibitors (TKIs) within 9–14 months of therapy. Recently, EGFR‐mutated NSCLC has demonstrated the potential for heterogeneity; therefore, the manner of clonal heterogeneity may impact the duration of progression‐free and overall survival and other parameters affecting EGFR‐TKI treatment efficacy. However no predictive biomarker of these favorable treatment efficacies has been identified to date. The exosome‐focused translational research for afatinib (EXTRA) study aims to identify a novel predictive biomarker and a resistance marker for afatinib by analyzing data from association studies of the clinical efficacy of afatinib and four “OMICs” (genomics, proteomics, epigenomics, and metabolomics) using peripheral blood from patients treated with afatinib. This study aims to: (i) conduct comprehensive multi‐OMIC analyses in a prospective clinical trial, and (ii) focus on both sera/plasma and exosome as a source for OMIC analyses to identify a novel predictor of the efficacy of a specific drug. To eliminate the carryover bias of prior treatment, systemic treatment‐naïve patients were enrolled. The candidates to be screened for biomarkers comprise a discovery cohort of 60 patients and an independent validation cohort of 40 patients. The EXTRA study is the first trial to screen novel biomarkers of longer treatment efficacy of EGFR‐TKIs using four‐OMICs analyses, focusing on both “naked or free” molecules and “capsulated” exosomal components in serially collected peripheral blood.

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MA04.05 P53 Non-Disruptive Mutation is a Negative Predictive Factor for OS and PFS in EGFR M+ NSCLC Treated with TKI

Cited by 2 publications

References 0 publications

The Presence of Concomitant Mutations Affects the Activity of EGFR Tyrosine Kinase Inhibitors in EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC) Patients

The Presence of Concomitant Mutations Affects the Activity of EGFR Tyrosine Kinase Inhibitors in EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC) Patients

Prospective exosome‐focused translational research for afatinib study of non‐small cell lung cancer patients expressing EGFR (EXTRA study)

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