Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology

Archives of Pathology & Laboratory Medicine, Journal Year: 2018, Volume and Issue: 142(3), P. 321 - 346

Published: Jan. 22, 2018

Context.— In 2013, an evidence-based guideline was published by the College of American Pathologists, International Association for Study Lung Cancer, and Molecular Pathology to set standards molecular analysis lung cancers guide treatment decisions with targeted inhibitors. New evidence has prompted evaluation additional laboratory technologies, targetable genes, patient populations, tumor types testing. Objective.— To systematically review update 2013 affirm its validity; assess new genetic discoveries, therapies; issue update. Design.— The convened expert panel develop help define key questions literature search terms, abstracts full articles, draft recommendations. Results.— Eighteen recommendations were drafted. also updated 3 from guideline. Conclusions.— largely reaffirmed allow testing cytology samples, require improved assay sensitivity, recommend against use immunohistochemistry EGFR Key include ROS1 all adenocarcinoma patients; inclusion genes (ERBB2, MET, BRAF, KRAS, RET) laboratories that perform next-generation sequencing panels; as alternative fluorescence in situ hybridization ALK and/or testing; 5% sensitivity assays T790M mutations patients secondary resistance inhibitors; cell-free DNA “rule in” when tissue is limited or hard obtain.

Language: Английский

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Application of Cell-free DNA Analysis to Cancer Treatment

New England Journal of Medicine, Journal Year: 2018, Volume and Issue: 379(18), P. 1754 - 1765

Published: Oct. 31, 2018

Interview with Dr. Ryan Corcoran on the potential clinical applications of cell-free DNA analysis in patients cancer. (10:36)Download The capacity to detect new cancers, treatment-resistant variants, and tumor heterogeneity by noninvasive technology basis blood promises revolutionize cancer detection, prevention, treatment.

Language: Английский

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Circulating Tumor DNA Analysis in Patients With Cancer: American Society of Clinical Oncology and College of American Pathologists Joint Review

Journal of Clinical Oncology, Journal Year: 2018, Volume and Issue: 36(16), P. 1631 - 1641

Published: March 5, 2018

Purpose Clinical use of analytical tests to assess genomic variants in circulating tumor DNA (ctDNA) is increasing. This joint review from ASCO and the College American Pathologists summarizes current information about clinical ctDNA assays provides a framework for future research. Methods An Expert Panel conducted literature on solid tumors, including pre-analytical variables, validity, interpretation reporting, validity utility. Results The search identified 1,338 references. Of those, 390, plus 31 references supplied by Panel, were selected full-text review. There 77 articles inclusion. Conclusion evidence indicates that testing optimally performed plasma collected cell stabilization or EDTA tubes, with tubes processed within 6 hours collection. Some have demonstrated utility certain types advanced cancer; however, there insufficient majority cancer. Evidence shows discordance between results genotyping specimens supports tissue confirm undetected tests. no little early-stage cancer, treatment monitoring, residual disease detection. suggest are useful cancer screening, outside trial. Given rapid pace research, re-evaluation will shortly be required, along development tools guidance practice.

Language: Английский

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Management of acquired resistance to EGFR TKI–targeted therapy in advanced non-small cell lung cancer

Molecular Cancer, Journal Year: 2018, Volume and Issue: 17(1)

Published: Feb. 15, 2018

Recent advances in diagnosis and treatment are enabling a more targeted approach to treating lung cancers. Therapy targeting the specific oncogenic driver mutation could inhibit tumor progression provide favorable prognosis clinical practice. Activating mutations of epidermal growth factor receptor (EGFR) non-small cell cancer (NSCLC) predictive for EGFR tyrosine kinase inhibitors (TKIs) treatment. For patients with EGFR-exon 19 deletions or an exon 21 Leu858Arg mutation, standard first-line is first-generation (gefitinib, erlotinib), second-generation (afatinib) TKIs. TKIs improve response rates, time progression, overall survival. Unfortunately, mutant develop disease after median 10 14 months on TKI. Different mechanisms acquired resistance have been reported. Optimal various not yet clearly defined, except T790M mutation. Repeated tissue biopsy important explore mechanisms, but it has limitations risks. Liquid valid alternative re-biopsy. Osimertinib approved T790M-positive NSCLC other TKI-resistant combination therapy may be considered. In addition, use immunotherapy evolved rapidly. Understanding clarifying biology EGFR-mutant guide future drug development, leading precise

Language: Английский

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Assessment of Resistance Mechanisms and Clinical Implications in Patients WithEGFRT790M–Positive Lung Cancer and Acquired Resistance to Osimertinib

JAMA Oncology, Journal Year: 2018, Volume and Issue: 4(11), P. 1527 - 1527

Published: Aug. 2, 2018

Osimertinib mesylate is used globally to treat EGFR-mutant non-small cell lung cancer (NSCLC) with tyrosine kinase inhibitor resistance mediated by the EGFR T790M mutation. Acquired osimertinib a growing clinical challenge that poorly understood.To understand molecular mechanisms of acquired and their behavior.Patients advanced NSCLC who received for T790M-positive prior were identified from multi-institutional cohort (n = 143) confirmatory trial (NCT01802632) 110). Next-generation sequencing tumor biopsies after was performed. Genotyping plasma cell-free DNA studied as an orthogonal approach, including serial samples when available. The study analysis finalized on November 9, 2017.Mechanisms association time treatment discontinuation osimertinib.Of 143 patients evaluated, 41 (28 [68%] women) had next-generation osimertinib. Among 13 (32%) maintained at resistance, C797S seen in 9 (22%). 28 individuals (68%) loss T790M, range competing detected, novel such KRAS mutations targetable gene fusions. Time shorter (6.1 vs 15.2 months), suggesting emergence pre-existing resistant clones; this finding confirmed validation 110 genotyping performed resistance. In studies levels mutant EGFR, associated smaller decrease driver mutation 1 3 weeks therapy (100% 83% decrease; P .01).Acquired early mechanisms. These data provide evidence heterogeneity need strategies can overcome multiple concomitant or preventing

Language: Английский

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Mechanisms of acquired resistance to first- and second-generation EGFR tyrosine kinase inhibitors

Annals of Oncology, Journal Year: 2018, Volume and Issue: 29, P. i10 - i19

Published: Jan. 1, 2018

Language: Английский

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Clinical Cancer Advances 2017: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology

Journal of Clinical Oncology, Journal Year: 2017, Volume and Issue: 35(12), P. 1341 - 1367

Published: Feb. 23, 2017

A MESSAGE FROM ASCO’S PRESIDENT I am pleased to present Clinical Cancer Advances 2017, which highlights the most promising advances in patient-oriented cancer research over past year. The report gives us an opportunity reflect on what exciting time it is for and how swiftly our understanding of has improved. One year ago, White House announced national Moonshot program accelerate progress against cancer. This shared vision reinvigorated community, identified new areas scientific collaboration, raised ambitions regarding may be possible beyond we have already made. When entered field 35 years could not imagined where would today. We can now detect earlier, target treatments more effectively, manage adverse effects effectively enable patients live better, fulfilling lives. Today, two three people with at least 5 after diagnosis, up from roughly one 1970s. resulted decades incremental that collectively expanded molecular underpinnings There no better current example this than ASCO’s 2017 Advance Year: Immunotherapy 2.0. Over last year, there been a wave successes immunotherapy. Research proven approach effective wide range hard-to-treat advanced cancers previously considered intractable. Researchers are working identify biologic markers help increase effectiveness treatment determine who likely benefit knowledge will oncologists make evidence-based decisions so as many might type treatment. Each successive advance builds previous hard work generations basic, translational, clinical researchers. Importantly, described without individuals volunteered participate trials part their To turn moonshot into meaningful advances, need sustained, robust federal funding continued innovation. Approximately 30% highlighted was funded, part, through dollars appropriated National Institutes Health or Institute. Without investment—unique internationally scale, duration, impact decades—I fear lose forward momentum needed further see report. Federal lawmakers fuel by advancing initiatives facilitate use big data achieve common good high-quality care all patients. Such programs, like CancerLinQ, rapidly pace dramatically expand reach millions living today do future. investment yield medical, scientific, economic, societal benefits come. Much still lies ahead. Many questions remain about develops spreads best treat it. As you read hope inspired gains community made promise era just horizon. Daniel F Hayes, MD, FASCO, FACP ASCO President, 2016

Language: Английский

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Liquid Biopsy for Advanced Non-Small Cell Lung Cancer (NSCLC): A Statement Paper from the IASLC

Journal of Thoracic Oncology, Journal Year: 2018, Volume and Issue: 13(9), P. 1248 - 1268

Published: June 6, 2018

Language: Английский

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Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors

Journal of Thoracic Oncology, Journal Year: 2018, Volume and Issue: 13(3), P. 323 - 358

Published: Jan. 25, 2018

Language: Английский

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Osimertinib in Pretreated T790M-Positive Advanced Non–Small-Cell Lung Cancer: AURA Study Phase II Extension Component

Journal of Clinical Oncology, Journal Year: 2017, Volume and Issue: 35(12), P. 1288 - 1296

Published: Feb. 21, 2017

Purpose Osimertinib is an irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) selective for both EGFR-TKI sensitizing ( EGFRm) and T790M resistance mutations. AURA (NCT01802632) a phase I/II clinical trial to determine the dose, safety, efficacy of osimertinib. This article reports results from II extension component. Patients Methods with EGFR-TKI–pretreated EGFRm- T790M-positive advanced non–small-cell lung cancer (NSCLC) received once-daily osimertinib 80 mg. status was confirmed by central testing tumor sample taken after most recent disease progression. asymptomatic, stable CNS metastases that did not require corticosteroids were allowed enroll. The primary end point objective response rate (ORR) independent radiology assessment. Secondary points control rate, duration response, progression-free survival (PFS), safety. Patient-reported outcomes comprised exploratory objective. Results In total, 201 patients treatment, median treatment 13.2 months at time data cutoff (November 1, 2015). evaluable (n = 198), ORR 62% (95% CI, 54% 68%), 90% 85 94). Median in 122 responding 15.2 11.3 calculable). PFS 12.3 9.5 13.8). common possibly causally related adverse events (investigator assessed) diarrhea (43%; grade ≥ 3, < 1%) rash (grouped terms; 40%; 1%). Interstitial terms) reported eight (4%; n 2; 3; 5, 3). Conclusion EGFRm NSCLC who progress provides high ORR, encouraging PFS, durable response.

Language: Английский

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