Final PFS, updated OS and safety data from the randomised, phase III ALEX study of alectinib (ALC) versus crizotinib (CRZ) in untreated advanced ALK+ NSCLC

Mok, T.; Shaw, Alice T.; Camidge, Ross; Gadgeel, Shirish M.; Rosell, R.; Dziadziuszko, Rafał; Kim, D.-W.; Pérol, Maurice; Ou, Sai Hong Ignatius; Bordogna, Walter; Smoljanović, Vlatka; Hilton, Magalie; Peters, Solange

doi:10.1093/annonc/mdz260.006

Cited by 19 publications

(22 citation statements)

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“…Alectinib is a second-generation ALK inhibitor and has demonstrated increased efficiency to crizotinib in terms of 12-month overall survival without events (68.4 vs. 48.7%) (hazard ratio (HR) for death or progression of 0.47 (95% CI 0.34–0.65), p < 0.001) [ 23 ]. Recently, updated global survival data have been reported, with a 4-year survival rate of 64.5% (95% CI 55.6–73.4) in the alectinib arm and 52.2% (95% CI 42.6–64.8) in the crizotinib arm [ 24 ]. The effectiveness of this drug is particularly demonstrated by the control of brain metastases or the time until the onset of brain metastases [ 25 , 26 , 27 , 28 ].…”

Section: Alk Inhibitorsmentioning

confidence: 99%

Combining Radiation Therapy with ALK Inhibitors in Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer (NSCLC): A Clinical and Preclinical Overview

Antoni

Burckel

Noël

2021

Cancers

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Over the past years, the identification of genetic alterations in oncogenic drivers in non-small cell lung cancer (NSCLC) has significantly and favorably transformed the outcome of patients who can benefit from targeted therapies such as tyrosine kinase inhibitors. Among these genetic alterations, anaplastic lymphoma kinase (ALK) rearrangements were discovered in 2007 and are present in 3–5% of patients with NSCLC. In addition, radiotherapy remains one of the cornerstones of NSCLC treatment. Moreover, improvements in the field of radiotherapy with the use of hypofractionated or ablative stereotactic radiotherapy have led to a better outcome for localized or oligometastatic NSCLC. To date, the effects of the combination of ALK inhibitors and radiotherapy are unclear in terms of safety and efficacy but could potently improve treatment. In this manuscript, we provide a clinical and preclinical overview of combining radiation therapy with ALK inhibitors in anaplastic lymphoma kinase-positive non-small cell lung cancer.

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Section: Alk Inhibitorsmentioning

confidence: 99%

Combining Radiation Therapy with ALK Inhibitors in Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer (NSCLC): A Clinical and Preclinical Overview

Antoni

Burckel

Noël

2021

Cancers

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“…67 In a recent update, for those with CNS metastases, mPFS was 25.4 months for alectinib versus 7.4 months for crizotinib (HR 0.37, 95% CI 0.23-0.58). 70 In addition to activity against L1196M-gatekeeper mutation, alectinib is also active against other secondary mutations, such as G1269A. 34,57 Unfortunately, similarly to crizotinib and ceritinib, eventual resistance to alectinib is unavoidable.…”

Section: Alectinibmentioning

confidence: 99%

<p>Optimal Care for Patients with Anaplastic Lymphoma Kinase (ALK)–Positive Non–Small Cell Lung Cancer: A Review on the Role and Utility of ALK Inhibitors</p>

Singh

Chen

2020

CMAR

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The treatment of advanced non-small-cell lung cancer (NSCLC) has undergone a paradigm shift in the last decade. Molecular characterization of the disease has led to the rapid development of personalized medicine and swift delivery of targeted therapies to patients. The discovery of the anaplastic lymphoma kinase (ALK) gene in patients with NSCLC has resulted in rapid bench-bedside transition of several active drugs, with several others currently in clinical trials. After the first-generation ALK inhibitor crizotinib, nextgeneration ALK inhibitors have entered clinical applications for ALK-rearranged NSCLC. Ceritinib, alectinib, and brigatinib have all received approval for ALK-positive patients who have failed prior crizotinib, as well as first-line therapy in treatment-naïve patients based on favorable efficacy. Most recently, lorlatinib, a potent, newer-generation ALK inhibitor, has been approved as second-or third-line treatment. These advances have led to better patient outcomes, but concurrently have led to several crucial unanswered questions about optimal care for ALK-positive NSCLC patients. The ultimate acquisition of resistance to ALKinhibitor therapy poses a challenge to ongoing research efforts, in addition to the routine management of these patients in the clinic. This review provides a summary of the clinical development of crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib and highlights current management paradigms, current and evolving clinical information, emerging clinical decision-making and sequencing of therapy in advanced, metastatic, or recurrent ALK-positive NSCLC.

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“…Также отмечен более благоприятный профиль безопасности в группе пациентов, получавших алектиниб. При этом по сравнению с кризотинибом, алектиниб на 84% (p<0,0001; ОР = 0,16) снижал вероятность прогрессирования опухоли в головной мозг вне зависимости от наличия метастазов в ЦНС до начала терапии [12,13].…”

Section: Conflict Of Interestunclassified

“…Такие беспрецедентные результаты являются веским основанием для предпочтительного использования алектиниба в лечении этой категории пациентов. При этом приоритетным местом использования алектиниба является его применение в 1-й линии терапии ALK-положительных пациентов с распространенным НМРЛ [13].…”

Section: Conflict Of Interestunclassified

Clinical case of prolonged use of alectinib in the treatment of ALK-positive NSCLC

et al. 2019

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Резюме Транслокация ALK относится к редким генетическим нарушениям, лежащим в основе развития рака легкого. Как правило, эти пациенты-молодые люди, с отсутствием или незначительным опытом курения, которым диагноз ставится на поздней стадии болезни, когда уже имеются отдаленные метастазы: часто поражаются печень и головной мозг. Но даже у таких больных с ALK-позитивным немелкоклеточным раком легкого (НМРЛ) при правильном выборе лечебной тактики можно добиться значимого улучшения выживаемости при применении ингибиторов ALK. Первым ингибитором ALK, доказавшим свою противоопухолевую активность, был кризотиниб (Xalkori). Однако, несмотря на начальный выраженный противоопухолевый эффект, у большинства больных через 1-2 года приема к кризотинибу развивается лекарственная резистентность. В этом случае назначение препаратов второго поколения алектиниба (Alecensa) и церитиниба (Zykadia) у половины больных позволяет достичь объективного ответа. Максимальный противоопухолевый эффект достигается при назначении новых ингибиторов ALK в первую линию. Так, на сегодняшний день применение алектиниба в первой линии терапии демонстрирует наилучшие долгосрочные результаты: медиана времени без прогрессирования более 34 месяцев, 4-летняя общая выживаемость-64,5%. Отмечена высокая активность препарата у больных с метастазами в головном мозге. Терапия алектинибом не только обладает преимуществом в отношении показателей выживаемости перед кризотинибом, но и имеет приемлемый профиль безопасности. Это открывает новые перспективы в лечении ALK-позитивных больных.

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Final PFS, updated OS and safety data from the randomised, phase III ALEX study of alectinib (ALC) versus crizotinib (CRZ) in untreated advanced ALK+ NSCLC

Cited by 19 publications

References 0 publications

Combining Radiation Therapy with ALK Inhibitors in Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer (NSCLC): A Clinical and Preclinical Overview

Combining Radiation Therapy with ALK Inhibitors in Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer (NSCLC): A Clinical and Preclinical Overview

<p>Optimal Care for Patients with Anaplastic Lymphoma Kinase (ALK)–Positive Non–Small Cell Lung Cancer: A Review on the Role and Utility of ALK Inhibitors</p>

Clinical case of prolonged use of alectinib in the treatment of ALK-positive NSCLC

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