The 2021 Global Lung Cancer Therapy Landscape

Deb, Dhruba; Moore, Amy; Roy, Upal

doi:10.1016/j.jtho.2022.03.018

Cited by 31 publications

(23 citation statements)

References 11 publications

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“…In Western countries, most EGFR-mutant patients are nowadays treated with Osimertinib as a first-line EGFR TKI treatment. However, as the less expensive first- and second-generation TKIs are still in use in many (developing) countries, this study remains relevant [ 37 , 38 , 39 , 40 ]. Moreover, our finding that a pre-existing T790M resistant mutation is very rare may be generalized to other TKI-related resistance mutations.…”

Section: Discussionmentioning

confidence: 99%

The Presence of EGFR T790M in TKI-Naïve Lung Cancer Samples of Patients Who Developed a T790M-Positive Relapse on First or Second Generation TKI Is Rare

Kok

Tan

et al. 2022

Cancers

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EGFR-mutated non-small cell lung cancer (NSCLC) patients can be effectively treated with tyrosine kinase inhibitors (TKI) but frequently present with an EGFR T790M resistance mutation at relapse. We aimed to screen for T790M in pre-treatment formalin-fixed and paraffin-embedded (FFPE) tissue samples of patients with a confirmed T790M mutation at progression. We analyzed 33 pre-treatment DNA samples of NSCLC patients who progressed upon TKI between 2013 to 2019. To establish storage-time dependent formalin fixation-induced background levels for C>T mutations, we analyzed DNA isolated from archival (stored >1 year, n = 22) and recently generated (stored <1 month, n = 11) FFPE samples and included DNA isolated from white blood cells (WBC) (n = 24) as controls. DNA samples were analyzed by droplet digital (dd)PCR, and positivity was defined by outlier detection according to Grubb’s criterion. The T790M background allele frequency levels were 0.160% in DNA isolated from archival-FFPE, 0.100% in fresh FFPE, and 0.035% in WBC. Progression-free survival (PFS) time of the single T790M positive patient was 9 months, while T790M negative patients had a median PFS of 10 months (range 2–27). Proper storage time matched FFPE control samples are essential for reliable detection of T790M mutation at low VAF. The presence of EGFR T790M mutations in pre-TKI samples is rare, even in patients who progressed with EGFR T790M mutations.

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Section: Discussionmentioning

confidence: 99%

The Presence of EGFR T790M in TKI-Naïve Lung Cancer Samples of Patients Who Developed a T790M-Positive Relapse on First or Second Generation TKI Is Rare

Kok

Tan

et al. 2022

Cancers

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“…NSCLC is often diagnosed at an advanced stage and has a poor prognosis [ 4 ]. Approximately 60% of patients with advanced NSCLC subtypes have specific molecular changes that may be suitable for targeted therapy [ 5 ].…”

Section: Non-small Cell Lung Cancermentioning

confidence: 99%

Biomarker-Targeted Therapies in Non–Small Cell Lung Cancer: Current Status and Perspectives

Guo

Zhang

Qin

et al. 2022

Cells

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Non-small-cell lung cancer (NSCLC) is one of the most common malignancies and the leading causes of cancer-related death worldwide. Despite many therapeutic advances in the past decade, NSCLC remains an incurable disease for the majority of patients. Molecular targeted therapies and immunotherapies have significantly improved the prognosis of NSCLC. However, the vast majority of advanced NSCLC develop resistance to current therapies and eventually progress. In this review, we discuss current and potential therapies for NSCLC, focusing on targeted therapies and immunotherapies. We highlight the future role of metabolic therapies and combination therapies in NSCLC.

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“…Iš 309 tirtų taikinių terapijos vaistų, proliferacinių signalų inhibitoriai sudaro didžiausią dalį -166 junginiai, iš kurių 87 (52 proc.) tirti antrosios arba trečiosios fazės klinikiniuose tyrimuose [5]. Ne imunoonkologiniai vaistai -ne vien TKI.…”

Section: Farmakoterapija Atvejų Nustatomas Nesmulkiųjų Ląstelių Plauč...unclassified

ROS1 teigiamo nesmulkiųjų ląstelių plaučių vėžio gydymo entrektinibu veiksmingumas ir saugumas

Miliauskas

2022

PIA

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Genų pertvarkymai, paveikiantys ROS1 receptoriaus tirozino kinazę, gali sąlygoti nuolat aktyvių sulietų onkoproteinų atsiradimą. ROS1 suliejimai (angl. fusions) randami esant įvairiems navikams ir būna 1–2 proc. nesmulkiųjų ląstelių plaučių vėžio (NSLPV) atvejų. Nustačius ROS1 teigiamą NSLPV, iki 40 proc. pažengusios ligos atvejų aptinkamos centrinės nervų sistemos (CNS) metastazės. Entrektinibas yra patvirtintas tirozino kinazės inhibitorius ROS1 teigiamam NSLPV gydyti. Straipsnyje pateikiami atnaujinti integruoti klinikinių tyrimų ALKA-372-001, STARTRK-1 ir STARTRK-2 duomenys, į kuriuos įtraukti 168 sergantieji ROS1 teigiamu NSLPV ir dar negydyti pacientai. Vidutinis išgyvenamumo stebėsenos laikotarpis buvo 29,1 mėn. (interkvartilinis intervalas 21,8–35,9). Objektyvaus atsako dažnis buvo 68 proc. (95 proc. pasikliautinasis intervalas (PI) 60,2–74,8); vidutinė atsako trukmė – 20,5 mėn. Vidutinis išgyvenamumas be ligos progresavimo buvo 15,7 mėn., o vidutinis bendrasis išgyvenamumas – 47,8 mėn. 25 pacientams su išmatuojamomis CNS metastazėmis objektyvus intrakranijinio atsako dažnis buvo 80 proc. (95 proc PI: 59,3–93,2), vidutinė intrakranijinio atsako trukmė buvo 12,9 mėn., vidutinis išgyvenamumas be ligos progresavimo – 8,8 mėn. Tarp 18 pacientų, kuriems, gydant krizotinibu, liga progresavo tik CNS, toliau gydant entrektinibu, dviem atvejais pasiektas dalinis atsakas (11 proc.), o keturiais – stabili liga (22 proc.). Šios kohortos septynių pacientų subgrupėje vienam pacientui (14 proc.) buvo fiksuotas dalinis objektyvus intrakranijinis atsakas. Entrektinibas yra veiksmingas vaistas, leidžiantis prailginti išgyvenamumą, esant ROS1 teigiamam NSLPV. Pacientams, kuriems, gydant krizotinibu, liga progresavo tik CNS, vaisto veikimas buvo nepakankamai veiksmingas.

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The 2021 Global Lung Cancer Therapy Landscape

Cited by 31 publications

References 11 publications

The Presence of EGFR T790M in TKI-Naïve Lung Cancer Samples of Patients Who Developed a T790M-Positive Relapse on First or Second Generation TKI Is Rare

The Presence of EGFR T790M in TKI-Naïve Lung Cancer Samples of Patients Who Developed a T790M-Positive Relapse on First or Second Generation TKI Is Rare

Biomarker-Targeted Therapies in Non–Small Cell Lung Cancer: Current Status and Perspectives

ROS1 teigiamo nesmulkiųjų ląstelių plaučių vėžio gydymo entrektinibu veiksmingumas ir saugumas

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