Osimertinib in UntreatedEGFR-Mutated Advanced Non–Small-Cell Lung Cancer

New England Journal of Medicine, Journal Year: 2017, Volume and Issue: 378(2), P. 113 - 125

Published: Nov. 18, 2017

Osimertinib is an oral, third-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that selectively inhibits both EGFR-TKI–sensitizing and EGFR T790M resistance mutations. We compared osimertinib with standard EGFR-TKIs in patients previously untreated, mutation–positive advanced non–small-cell lung cancer (NSCLC).

Language: Английский

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Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer

British Journal of Cancer, Journal Year: 2019, Volume and Issue: 121(9), P. 725 - 737

Published: Sept. 29, 2019

Abstract Osimertinib is an irreversible, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that highly selective for EGFR- activating mutations as well the EGFR T790M mutation in patients with advanced non-small cell lung cancer (NSCLC) oncogene addiction. Despite documented efficacy of osimertinib first- and second-line settings, inevitably develop resistance, no further clear-cut therapeutic options to date other than chemotherapy locally ablative therapy selected individuals. On account high degree tumour heterogeneity adaptive cellular signalling pathways NSCLC, acquired resistance heterogeneous, encompassing - dependent EGFR-independent mechanisms. Furthermore, data from repeat plasma genotyping analyses have highlighted differences frequency preponderance mechanisms when administered a front-line versus setting, underlying discrepancies selection pressure clonal evolution. This review summarises molecular mutated including MET/HER2 amplification, activation RAS–mitogen-activated protein (MAPK) or RAS–phosphatidylinositol 3-kinase (PI3K) pathways, novel fusion events histological/phenotypic transformation, discussing current evidence regarding potential new approaches counteract resistance.

Language: Английский

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The emerging treatment landscape of targeted therapy in non-small-cell lung cancer

Signal Transduction and Targeted Therapy, Journal Year: 2019, Volume and Issue: 4(1)

Published: Dec. 17, 2019

Abstract Lung cancer is one of the most common in world. In 2018, there were over 2 million new cases lung and 1.7 deaths attributed to cancer. Targeted therapy has emerged as an important mean disease management for patients with non-small-cell (NSCLC). Herein, we review analyze recent literature, discuss targeting pathways ongoing clinical trials Chemotherapy no longer best available treatment all patients. Therapeutic decisions should be guided by understanding molecular features patient’s tumor tissues. The future gains will likely emerge from finding optimal ways combining targeted therapy, immunotherapy, chemotherapy.

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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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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Treatment for Brain Metastases: ASCO-SNO-ASTRO Guideline

Journal of Clinical Oncology, Journal Year: 2021, Volume and Issue: 40(5), P. 492 - 516

Published: Dec. 21, 2021

PURPOSE To provide guidance to clinicians regarding therapy for patients with brain metastases from solid tumors. METHODS ASCO convened an Expert Panel and conducted a systematic review of the literature. RESULTS Thirty-two randomized trials published in 2008 or later met eligibility criteria form primary evidentiary base. RECOMMENDATIONS Surgery is reasonable option metastases. Patients large tumors mass effect are more likely benefit than those multiple and/or uncontrolled systemic disease. symptomatic should receive local regardless used. For asymptomatic metastases, not be deferred unless deferral specifically recommended this guideline. The decision defer based on multidisciplinary discussion potential benefits harms that patient may experience. Several regimens were non–small-cell lung cancer, breast melanoma. no options, stereotactic radiosurgery (SRS) alone offered one four unresected excluding small-cell carcinoma. SRS surgical cavity two resected SRS, whole radiation therapy, their combination options other patients. Memantine hippocampal avoidance who have lesions 4 months expected survival. either Karnofsky Performance Status ≤ 50 < 70 do derive therapy. Additional information available at www.asco.org/neurooncology-guidelines .

Language: Английский

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Osimertinib As First-Line Treatment of EGFR Mutation–Positive Advanced Non–Small-Cell Lung Cancer

Journal of Clinical Oncology, Journal Year: 2017, Volume and Issue: 36(9), P. 841 - 849

Published: Aug. 25, 2017

Purpose The AURA study ( ClinicalTrials.gov identifier: NCT01802632) included two cohorts of treatment-naïve patients to examine clinical activity and safety osimertinib (an epidermal growth factor receptor [EGFR] –tyrosine kinase inhibitor selective for EGFR–tyrosine sensitizing [ EGFRm] EGFR T790M resistance mutations) as first-line treatment EGFR-mutated advanced non–small-cell lung cancer (NSCLC). Patients Methods Sixty with locally or metastatic EGFRm NSCLC received 80 160 mg once daily (30 per cohort). End points investigator-assessed objective response rate (ORR), progression-free survival (PFS), evaluation. Plasma samples were collected at after experienced disease progression, defined by Response Evaluation Criteria in Solid Tumors (RECIST), investigate mechanisms. Results At data cutoff (November 1, 2016), median follow-up was 19.1 months. Overall ORR 67% (95% CI, 47% 83%) the 80-mg group, 87% 69% 96%) 160-mg 77% 64% 87%) across doses. Median PFS time 22.1 months 13.7 30.2 months) 19.3 26.0 20.5 15.0 26.1 Of 38 postprogression plasma samples, 50% had no detectable circulating tumor DNA. Nine 19 putative mechanisms, including amplification MET (n = 1); KRAS MEK1, KRAS, PIK3CA mutation 1 each); C797S 2); JAK2 HER2 exon 20 insertion 1). Acquired not detected. Conclusion Osimertinib demonstrated a robust prolonged NSCLC. There evidence acquired samples.

Language: Английский

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CNS Efficacy of Osimertinib in Patients With T790M-Positive Advanced Non–Small-Cell Lung Cancer: Data From a Randomized Phase III Trial (AURA3)

Journal of Clinical Oncology, Journal Year: 2018, Volume and Issue: 36(26), P. 2702 - 2709

Published: July 30, 2018

Purpose In patients with epidermal growth factor receptor ( EGFR) mutation-positive advanced non-small-cell lung cancer (NSCLC), there is an unmet need for EGFR-tyrosine kinase inhibitors improved CNS penetration and activity against metastases, either at initial diagnosis or time of progression. We report the first comparative evidence osimertinib efficacy versus platinum-pemetrexed from a phase III study (AURA3; ClinicalTrials.gov identifier: NCT02151981) in EGFR T790M-positive NSCLC who experience disease progression prior inhibitor treatment. Methods Patients asymptomatic, stable metastases were eligible enrollment randomly assigned 2:1 to 80 mg once daily platinum-pemetrexed. A preplanned subgroup analysis was conducted measurable and/or nonmeasurable lesions on baseline brain scan by blinded independent central neuroradiological review. The evaluable response set included only one more lesions. primary objective this rate (ORR). Results Of 419 treatment, 116 had lesions, including 46 At data cutoff (April 15, 2016), ORR 70% (21 30; 95% CI, 51% 85%) 31% (5 16; 11% 59%) (odds ratio, 5.13; 1.44 20.64; P = .015); 40% (30 75; 29% 52%) 17% (7 41; 7% 32%), respectively, 3.24; 1.33 8.81; .014). Median duration 8.9 months (95% 4.3 not calculable) 5.7 4.4 months) platinum-pemetrexed; median progression-free survival 11.7 5.6 months, respectively (hazard 0.32; 0.15 0.69; .004). Conclusion Osimertinib demonstrated superior NSCLC.

Language: Английский

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Non‐small cell lung cancer in China

Cancer Communications, Journal Year: 2022, Volume and Issue: 42(10), P. 937 - 970

Published: Sept. 8, 2022

In China, lung cancer is a primary type with high incidence and mortality. Risk factors for include tobacco use, family history, radiation exposure, the presence of chronic diseases. Most early-stage non-small cell (NSCLC) patients miss optimal timing treatment due to lack clinical presentations. Population-based nationwide screening programs are significant help in increasing early detection survival rates NSCLC China. The understanding molecular carcinogenesis identification oncogenic drivers dramatically facilitate development targeted therapy NSCLC, thus prolonging positive drivers. exploration immune escape mechanisms, programmed death protein 1 (PD-1)/programmed death-ligand (PD-L1) inhibitor monotherapy PD-1/PD-L1 plus chemotherapy have become standard care advanced Chinese Society Clinical Oncology's guidelines maintenance immunotherapy recommended locally after chemoradiotherapy. Adjuvant neoadjuvant chemoimmunotherapy will be approved resectable NSCLC. this review, we summarized recent advances China terms epidemiology, biology, pathology, pathogenesis, screening, diagnosis, therapy, immunotherapy.

Language: Английский

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Overcoming therapy resistance in EGFR-mutant lung cancer

Nature Cancer, Journal Year: 2021, Volume and Issue: 2(4), P. 377 - 391

Published: April 15, 2021

Language: Английский

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