AZD9291 in EGFR Inhibitor–Resistant Non–Small-Cell Lung Cancer

Jänne, Pasi A.; Yang, James Chih‐Hsin; Kim, Dong Wan; Planchard, David; Ohe, Yuichiro; Ramalingam, Suresh S.; Ahn, Myung Ju; Kim, Sang We; Su, Wu Chou; Horn, Leora; Haggstrom, Daniel; Felip, Enriqueta; Kim, Joo Hang; Frewer, Paul; Cantarini, Mireille; Brown, Kathryn H.; Dickinson, Paul; Ghiorghiu, Serban; Ranson, Malcolm R

doi:10.1056/nejmoa1411817

Cited by 1,853 publications

(1,566 citation statements)

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“…220,221,236 Data are emerging 237 that a second acquired resistance mutation, C797S, can arise in tumors that have progressed after osimertinib treatment for T790M disease, but these cases are so far rare and this mutation is poorly studied and not currently treatable, so testing for C797S is not recommended for routine management at this time.…”

Section: Recommendationmentioning

confidence: 99%

“…Such testing is particularly appropriate because third-generation EGFR inhibitors (eg, osimertinib) are proven to have significant benefit for T790M mutant cancers 221 and have been approved for this indication by health authorities around the world. Analysis of cfDNA or analysis of a new tissue biopsy is appropriate for EGFR T790M detection.…”

Section: Expert Consensus Opinionmentioning

confidence: 99%

See 1 more Smart Citation

Analytical Validation of BRAF Mutation Testing from Circulating Free DNA Using the Amplification Refractory Mutation Testing System

Aung

Donald

Ellison

et al. 2014

The Journal of Molecular Diagnostics

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Context: In 2013, an evidence-based guideline was published by the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology to set standards for the molecular analysis of lung cancers to guide treatment decisions with targeted inhibitors. New evidence has prompted an evaluation of additional laboratory technologies, targetable genes, patient populations, and tumor types for testing. Objective: To systematically review and update the 2013 guideline to affirm its validity; to assess the evidence of new genetic discoveries, technologies, and therapies; and to issue an evidence-based update. Design: The College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology convened an expert panel to develop an evidence-based guideline to help define the key questions and literature search terms, review abstracts and full articles, and draft recommendations. Results: Eighteen new recommendations were drafted. The panel also updated 3 recommendations from the 2013 guideline. Conclusions: The 2013 guideline was largely reaffirmed with updated recommendations to allow testing of cytology samples, require improved assay sensitivity, and recommend against the use of

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Section: Recommendationmentioning

confidence: 99%

Section: Expert Consensus Opinionmentioning

confidence: 99%

Analytical Validation of BRAF Mutation Testing from Circulating Free DNA Using the Amplification Refractory Mutation Testing System

Aung

Donald

Ellison

et al. 2014

The Journal of Molecular Diagnostics

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“…As regards the other new-generation TKIs, unfortunately the clinical development of both rociletinib and olmutinib has been recently stopped, even if both these agents had already received the FDA-break-through therapy designation in lung cancer. Despite the promising activity observed in phase I study (Jänne et al, 2015), the updated "confirmed" response rate to rociletinib dropped from 59% to 39% at 625 mg bid dose (n = 175) and to 25% at 500 mg bid dose (n = 156) in T790M-positive patients (Sequist et al, 2015;Goldman et al, 2016). These data, along with the high rate of G3-4 hyperglycemia and QTc prolongation reported in TIGERX trial, led to the FDA notification with the subsequent stopping of patients' enrollment in all ongoing trials with rociletinib.…”

Section: New Generation Egfr-tkismentioning

confidence: 92%

EGFR inhibition in NSCLC: New findings…. and opened questions?

Passiglia

Listì

Castiglia

et al. 2017

Critical Reviews in Oncology/Hematology

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The targeted inhibition of epidermal growth factor receptor (EGFR) has represented a milestone in the treatment of lung cancer. Several studies convincingly and consistently demonstrated a significant superiority of EGFR-TKIs over standard platinum-chemotherapy in EGFR-mutated NSCLC patients, leading to the sequential approval of gefitinib, erlotinib and afatinib as new standard first-line clinical treatment. To date we are witnessing a second revolution in the management of EGFR-positive NSCLC thanks to the development of new treatment strategies aiming to overcome acquired resistance to TKIs and ultimately improve patients’ outcomes. In this review we summarize the most important recent findings regarding EGFR-inhibition in NSCLC, highlighting the current unsolved questions on the selection of the best TKI in first-line, which therapy can be combined with upfront EGFR-TKIs, how to overcome acquired resistance, and which are the clinical applications of liquid biopsy

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“…The understanding of the molecular pathology of tumours in unprecedented detail coupled with modern drugs and associated diagnostic technologies to select patients has enabled tangible improvements in survival rates in some cancer types 10-17 ; particularly exemplified in patients with Non Small Cell Lung Cancer (NSCLC) 13,16 . More recently, significant durable responses to immune modulatory therapies are emerging in ~15% of patients.…”

Section: Principles and Evolution Of Clinical Trialsmentioning

confidence: 99%

“…Such advances have ushered in a new era of therapeutics that target specific molecular processes. Although we have had some dramatic successes [8][9][10][11][12][13][14][15][16][17] , the overall strategy remains in its infancy 18 . The central premise of precision medicine is that by matching a drug and its mechanism of action to select patients we can offer greater potential for durable clinical benefit -often referred to as "matching the right drug to the right patient".…”

Section: Introductionmentioning

confidence: 99%

Patient-centric trials for therapeutic development in precision oncology

Biankin

Piantadosi

Hollingsworth

2015

Nature

246

184

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Our increasing understanding of the molecular pathology of disease, particularly through genomic studies, has created significant opportunities for the development of therapeutics that specifically target discrete molecular subclasses, but equally, has generated substantial challenges in how to develop and implement these strategies. Variously termed personalised, stratified, individualised or precision medicine, the approach is centered on delivering the optimal therapy for an individual based on specific clinical and molecular features of their disease. The development of new therapeutics that target molecular mechanisms has driven considerable change and innovation in clinical trial strategies. We have made progress through improved efficiency and changes in clinical trial design, yet continued innovation through the modification of existing core paradigms in oncology drug development and clinical care are required to fully realise the promise of precision medicine.

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AZD9291 in EGFR Inhibitor–Resistant Non–Small-Cell Lung Cancer

Abstract: AZD9291 was highly active in patients with lung cancer with the EGFR T790M mutation who had had disease progression during prior therapy with EGFR tyrosine kinase inhibitors. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT01802632.).

Cited by 1,853 publications

References 26 publications

Analytical Validation of BRAF Mutation Testing from Circulating Free DNA Using the Amplification Refractory Mutation Testing System

Analytical Validation of BRAF Mutation Testing from Circulating Free DNA Using the Amplification Refractory Mutation Testing System

EGFR inhibition in NSCLC: New findings…. and opened questions?

Patient-centric trials for therapeutic development in precision oncology

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