News - EGFR T790M + KRAS mutation

over3years

Clinical Benefit of Tyrosine Kinase Inhibitors in Advanced Lung Cancer with EGFR-G719A and Other Uncommon EGFR Mutations. (PubMed, Oncologist)

Afatinib treatment at 40 mg daily is associated with high rates of adverse events and dose reductions; alternative strategies including pulse intermittent dosing should be evaluated prospectively. Osimertinib (with favorable safety profile and intracranial penetration) has shown promising results in this population in a phase II trial from South Korea; additional trials are ongoing.

over 3 years ago

Clinical • Journal

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR L861Q • EGFR L858R + EGFR T790M • EGFR G719X • EGFR S768I • EGFR G719A • EGFR G719X + EGFR S768I • EGFR L861Q + EGFR G719X • EGFR L858R + EGFR exon 19 deletion • EGFR T790M + KRAS mutation • EGFR mutation + EGFR T790M • EGFR G719A + EGFR S768I • EGFR L858R + EGFR S768I • EGFR exon 19 deletion + EGFR S768I • EGFR T790M + exon 19 deletion

Tagrisso (osimertinib) • Gilotrif (afatinib)

over3years

Acquired resistance to osimertinib in patients with non-small-cell lung cancer: mechanisms and clinical outcomes. (PubMed, J Cancer Res Clin Oncol)

The study revealed heterogeneous mechanisms of resistance to osimertinib in advanced NSCLC patients and their association with clinical outcomes. Patients who maintained T790M mutation or with EGFR-dependent resistance mechanism had longer clinical outcome benefits.

over 3 years ago

Clinical • Clinical data • Retrospective data • Journal

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

TP53 mutation • KRAS mutation • EGFR mutation • BRAF mutation • PIK3CA mutation • MET amplification • EGFR T790M • EGFR amplification • EGFR C797S • PIK3CA amplification • EGFR mutation + KRAS mutation • EGFR G724S • BRAF mutation + MET amplification • EGFR T790M + KRAS mutation • EGFR mutation + EGFR T790M • EGFR C796S • EGFR C797S + EGFR C796S • EGFR E758D • EGFR G796S • EGFR V802I • EGFR V834L • EGFR mutation + EGFR T790M + EGFR C797S • KRAS mutation + EGFR amplification

Tagrisso (osimertinib)

over3years

Mutational Portrait of Lung Adenocarcinoma in Brazilian Patients: Past, Present, and Future of Molecular Profiling in the Clinic. (PubMed, Front Oncol)

This report provides the first comprehensive actionable alteration portrait of LA in Brazil. The high rate of actionable alterations in EGFR and other driver genes in LA reinforces the need to incorporate TKI guided by molecular diagnostics into clinical routines for patients in both public and private healthcare systems.

over 3 years ago

Clinical • Journal

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)

KRAS mutation • EGFR mutation • BRAF mutation • NRAS mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR L858R + EGFR T790M • EGFR L858R + EGFR exon 19 deletion • EGFR T790M + KRAS mutation • EGFR T790M + exon 19 deletion

over3years

[VIRTUAL] Identification of targetable alterations using NGS-based liquid biopsy in NSCLC patients (ESMO 2020)

Funding: This study was supported by CB16/12/00350 and P118/00226 from ISCIII and Asociación de Mujeres de Apoyo al Cáncer de Mama (AMACMA). AM is recipient of PhD scholarship from Asociación Española Contra el Cáncer (AECC) Valencia Scientific Foundation.

over 3 years ago

Clinical • Liquid biopsy • Next-generation sequencing

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • RET (Ret Proto-Oncogene) • CDK4 (Cyclin-dependent kinase 4)

TP53 mutation • BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • HER-2 amplification • BRAF V600 • EGFR L858R • EGFR T790M • KRAS G12V • EGFR L858R + EGFR T790M • KRAS G12 • EGFR mutation + BRAF V600E • EGFR mutation + KRAS mutation • BRAF mutation + MET amplification • EGFR T790M + KRAS mutation • EGFR exon 2-7 deletion + EGFR amplification • EGFR mutation + EGFR T790M

Oncomine™ Pan-Cancer Cell-Free Assay

almost4years

Target-based genomic profiling of ctDNA from Chinese non-small cell lung cancer patients: a result of real-world data. (PubMed, J Cancer Res Clin Oncol)

In Chinese NSCLC patients, EGFR mutation was significantly associated with female, younger age (< 65 years), and adenocarcinoma. Genomic profiles of NSCLC were associated with the treatment history; TP53 mutation was significantly more frequent in the patients with history of radiochemotherapy/chemotherapy therapy. Various multiple genes co-mutation panels, especially EGFR and KRAS co-mutation, were observed in the ctDNA of Chinese NSCLC patients.

almost 4 years ago

Clinical • Retrospective data • Journal • Real-World Evidence

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

TP53 mutation • KRAS mutation • EGFR mutation • PIK3CA mutation • EGFR L858R • EGFR exon 19 deletion • EGFR L858R + EGFR T790M • KRAS G13 • EGFR L858R + EGFR exon 19 deletion • EGFR T790M + KRAS mutation • EGFR T790M + exon 19 deletion

almost4years

[VIRTUAL] A single institution experience with droplet digital polymerase chain reaction (dd-PCR) liquid biopsy (LB) for therapeutic decision in advanced solid tumors (AACR-II 2020)

Our results suggest that dd-PCR is a highly sensitive method and could be used for a routine laboratory detection of the important genomic variations to determine the targeted therapy in patients with varied advanced solid tumors.

almost 4 years ago

Clinical • Liquid biopsy • Polymerase Chain Reaction

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • EML4 (EMAP Like 4) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)

BRAF V600E • KRAS mutation • EGFR mutation • HER-2 amplification • NRAS mutation • PIK3CA mutation • BRAF V600 • EGFR L858R • EGFR T790M • KRAS G12V • KIT mutation • ALK fusion • ALK mutation • ER mutation • ROS1 fusion • EGFR L858R + EGFR T790M • KRAS G12 • PDGFRA mutation • EGFR T790M + KRAS mutation • ALK-ROS1 fusion

almost4years

[VIRTUAL] Combinations of SHP2 inhibitor to overcome RAS activation by receptor tyrosine kinases in response to ERK inhibition (AACR-II 2020)

Experimental procedures: The combination efficacy and synergy of TNO155 with EGF816 (a 3rd generation EGFR inhibitor), dabrafenib+trametinib or a tool KRAS G12C inhibitor (G12Ci) were respectively assessed in a number of EGFR mutant lung cancer models, BRAFV600E colorectal cancer models and KRASG12C lung and colorectal cancer models. Our findings suggest that SHP2 inhibition is an effective strategy to block the feedback activation of wild type and G12C KRAS, as well as NRAS and HRAS, by a variety of RTKs, in response to ERK inhibition. Given the mutant selective properties of those inhibitors we studied, the tolerability of their combinations with TNO155 is highly expected. Our data provide pre-clinical rationale to explore those TNO155 combinations in the corresponding cancer indications in clinic.

almost 4 years ago

Late-breaking abstract

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog) • FGFR (Fibroblast Growth Factor Receptor) • PTPRT (Protein tyrosine phosphatase receptor type T)

BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • BRAF V600 • MET amplification • EGFR C797S • KRAS amplification • NRAS G12 • BRAF mutation + MET amplification • EGFR T790M + KRAS mutation • HRAS G12C • BRAF amplification

Mekinist (trametinib) • Tafinlar (dabrafenib) • batoprotafib (TNO155) • nazartinib (EGF816)

almost4years

[VIRTUAL] Targeted DNA sequencing analysis to reveal genetic diversity and androgen-receptor alteration in advanced EGFR mutant lung adenocarcinoma. (ASCO 2020)

"We characterized the genetic landscape of advanced EGFR-mutant lung adenocarcinomas and further dissected concurrent mutated genes with EGFR driver mutations. Our findings provide a rational for polytherapy roadmap for testing in advanced EGFR-mutant lung cancer. Research Funding: U.S. National Institutes of Health"

almost 4 years ago

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • AR (Androgen receptor) • MAP2K1 (Mitogen-activated protein kinase kinase 1)

KRAS mutation • EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • RET fusion • NF1 mutation • EGFR L858R + EGFR T790M • MET mutation • EGFR G719A • EGFR exon 18 mutation • EGFR L858R + EGFR exon 19 deletion • EGFR T790M + KRAS mutation

MSK-IMPACT

almost4years

[VIRTUAL] Molecular profiling of lung adenocarcinoma using pleural effusion specimens. (ASCO 2020)

These results suggest that pleural effusions are important specimens for oncogene mutation analysis and enable targeted therapy for patients with lung adenocarcinoma. Research Funding: None

almost 4 years ago

Tumor Mutational Burden • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • EML4 (EMAP Like 4) • ARID1A (AT-rich interaction domain 1A) • KIF5B (Kinesin Family Member 5B) • CDK4 (Cyclin-dependent kinase 4) • CDK6 (Cyclin-dependent kinase 6) • BARD1 (BRCA1 Associated RING Domain 1)

PD-L1 expression • TP53 mutation • KRAS mutation • EGFR mutation • TMB-H • KRAS G12C • EGFR L858R • ARID1A mutation • ALK fusion • KIF5B-RET fusion • EGFR L858R + EGFR T790M • KRAS G12 • BARD1 mutation • EGFR T790M + KRAS mutation • HER-2 A775

almost4years

[VIRTUAL] BRAF fusion in lung cancer. (ASCO 2020)

BRAF fusion had low frequency in lung cancer and occurred at different stage during disease development. BRAF inhibitors maybe a potential strategy for BRAF fusion lung cancers. As TKIs resistance mechanism, BRAF fusion is a huge clinical challenge, indicate the importance of further research.

almost 4 years ago

Tumor Mutational Burden

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden)

BRAF V600E • KRAS mutation • EGFR mutation • TMB-H • BRAF V600 • EGFR L858R • TMB-L • EGFR C797S • EGFR L858R + EGFR T790M • BRAF fusion • EGFR C797S + EGFR T790M + EGFR L858R • EGFR T790M + KRAS mutation

almost4years

[VIRTUAL] Targeted PCR vs NGS for molecular diagnostic in solid tumors and liquid biopsies. How to choose in real-life. (ASCO 2020)

Independently of cost-effectiveness, using PCR reduces time to results and can accelerate the initiation of targeted therapy but restricts the range of analysis, while extensive NGS delays time to results but identifies additional biomarkers that could be useful for therapeutic stratification. Using liquid biopsy testing could be an alternative and allow dynamic molecular diagnostic at 1st line and during follow-up. Research Funding: None

almost 4 years ago

Clinical • Next-generation sequencing

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)

KRAS mutation • BRAF mutation • EGFR T790M • KIT mutation • EGFR T790M + KRAS mutation

almost4years

[VIRTUAL] A single institution experience with droplet digital polymerase chain reaction (dd-PCR) liquid biopsy (LB) for therapeutic decision in advanced solid tumors. (ASCO 2020)

almost 4 years ago

Clinical • Liquid biopsy • Polymerase Chain Reaction

BRAF V600E • KRAS mutation • EGFR mutation • HER-2 amplification • NRAS mutation • PIK3CA mutation • BRAF V600 • EGFR L858R • HER-2 mutation • EGFR T790M • KRAS G12V • KIT mutation • ALK fusion • ALK mutation • ER mutation • ROS1 fusion • EGFR L858R + EGFR T790M • KRAS G12 • PDGFRA mutation • EGFR T790M + KRAS mutation • ALK-ROS1 fusion

almost4years

[VIRTUAL] RELAY study of erlotinib (ERL) + ramucirumab (RAM) or placebo (PL) in EGFR-mutated metastatic non-small cell lung cancer (NSCLC): Biomarker analysis using circulating tumor DNA (ctDNA) in Japanese patients (pts). (ASCO 2020)

Though limited by sample size and likely inconsistent tumor shedding, this exploratory study identified potential differences in TP53, KRAS, ERBB2 and MET by demographics, treatment and/or time. Research Funding: Eli Lilly and Company

almost 4 years ago

Clinical

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • FGFR3 (Fibroblast growth factor receptor 3)

TP53 mutation • KRAS mutation • EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • PTEN mutation • FGFR3 mutation • EGFR L858R + EGFR T790M • MET mutation • EGFR L858R + EGFR exon 19 deletion • EGFR T790M + KRAS mutation • EGFR T790M + exon 19 deletion

erlotinib • Cyramza (ramucirumab)