Pooled Systemic Efficacy and Safety Data from the Pivotal Phase II Studies (NP28673 and NP28761) of Alectinib in ALK -positive Non-Small Cell Lung Cancer

Yang, James Chih‐Hsin; Ou, Sai Hong Ignatius; Petris, Luigi De; Gadgeel, Shirish M.; Gandhi, Leena; Kim, Dong Wan; Barlési, Fabrice; Govindan, Ramaswamy; Dingemans, Anne Marie C.; Crinò, Lucio; Léna, H.; Popat, Sanjay; Ahn, Jin Seok; Dansin, Éric; Golding, Sophie; Bordogna, Walter; Balas, Bogdana; Morcos, Peter N.; Zeaiter, Ali; Shaw, Alice T.

doi:10.1016/j.jtho.2017.06.070

Cited by 75 publications

(64 citation statements)

References 23 publications

(36 reference statements)

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“…Median rwPFS with ceritinib as second ALK TKI therapy was 5.43 months (n = 126) in our analysis, which is in line with the PFS reported in the ASCEND-5 (5.4 months [n = 115]), ASCEND-2 (5.7 months [n = 140]), and ASCEND-1 (6.9 months [n = 163]) clinical trials, respectively [19,32,33]. Similarly, our rwPFS result of 9.24 months (n = 106) for second-line alectinib is in line with the PFS reported for alectinib in the NP28673 and NP28761 trials (8.3 months n = 225]) [34]. However, results for rwPFS for second-line brigatinib and crizotinib retreatment in our analysis do differ from PFS reported in clinical trials (e.g., 11.32 months [n = 7] for brigatinib in our analysis vs. 16.7 months [n = 110] in the ALTA trial [35]).…”

Section: Discussionsupporting

confidence: 81%

Real-World Treatment Patterns and Progression-Free Survival Associated with Anaplastic Lymphoma Kinase (ALK) Tyrosine Kinase Inhibitor Therapies for ALK+ Non-Small Cell Lung Cancer

et al. 2020

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Background. Little is known about real-world treatment and outcomes of patients with anaplastic lymphoma kinasepositive (ALK+) advanced non-small cell lung cancer (NSCLC). Patients and Methods. This retrospective study of the Flatiron Health EHR-derived deidentified database included patients with a lung cancer diagnosis and confirmed advanced NSCLC who received ALK tyrosine kinase inhibitor (TKI) therapy (January 1, 2011, through June 30, 2018). Patient characteristics and treatment patterns were characterized. Real-world progression-free survival (rwPFS) and time to discontinuation were calculated using the Kaplan-Meier method. Results. First-line ALK TKI therapy was administered to 581 patients (27.5% had brain metastasis on or prior to initiation) and second-line ALK TKI therapy to 254 patients post crizotinib (45.7% had brain metastasis on or prior to second-line ALK TKI initiation). Crizotinib (84.6%; n = 492) was the most commonly administered first-line ALK TKI therapy. For second-line ALK TKI post crizotinib (n = 254), 49.6% received ceritinib, 41.7% received alectinib, 5.9% received crizotinib retreatment, and 2.8% received brigatinib. Median (95% confidence interval [CI]) rwPFS was 7.47 (6.48-8.32) months for first-line and 7.30 (5.72-8.42) months for second-line ALK TKI. Median (95% CI) rwPFS was significantly longer among first-line ALK TKI patients without than with brain metastasis (8.52 [7.57-10.59] vs. 4.97 [3.75-5.99] months; p < .0001) and patients with brain metastasis on or prior to first-line ALK TKI therapy had a significantly increased risk of progression (hazard ratio AE SE, 1.976 AE 0.112; p < .0001). Conclusion. Median rwPFS in patients with advanced ALK+ NSCLC was < 8 months for firstand second-line ALK TKI therapy and was even shorter in patients with brain metastasis, highlighting the need for more effective treatments in this patient population. The Oncologist 2020;25:867-877 Implications for Practice: Results presented herein describe real-world treatment of advanced ALK+ NSCLC with ALK TKI therapies from January 2011 through June 2018. Crizotinib was the most commonly prescribed first-line ALK TKI therapy in this patient population, but the majority of data analyzed were obtained prior to Food and Drug Administration approval of alectinib and ceritinib in the first-line ALK TKI setting. Physicians should monitor patients closely to help identify when a change in treatment should occur.

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Section: Discussionsupporting

confidence: 81%

Real-World Treatment Patterns and Progression-Free Survival Associated with Anaplastic Lymphoma Kinase (ALK) Tyrosine Kinase Inhibitor Therapies for ALK+ Non-Small Cell Lung Cancer

et al. 2020

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“…In pooled analyses from NP28673 and NP28761, alectinib showed activity against systemic and CNS disease in patients previously treated with crizotinib. 3,4 Alectinib demonstrates effective CNS penetration and is not a substrate for P-glycoprotein, which promotes efflux at the blood-brain barrier. 8 Responses in the alectinib Phase II studies were durable, lasting for longer than 1 year.…”

Section: Discussionmentioning

confidence: 99%

“…8 Responses in the alectinib Phase II studies were durable, lasting for longer than 1 year. 3 In the exploratory analyses presented here, we investigated how quickly patients can achieve benefit from alectinib. Systemic and CNS responses were rapid (median 6-8 weeks), and most patients achieved a response by the time they underwent their first scan.…”

Section: Discussionmentioning

confidence: 99%

“…A pooled analysis of data from these studies showed that alectinib achieved high overall response rates (51.3%, 95% confidence interval [CI] 44.0-58.6; data cutoff February 1, 2016 [NP28673] and January 22, 2016 [NP28761]), and that responses were durable (median 14.9 months). 3 Alectinib has also demonstrated consistent CNS efficacy. In a pooled analysis from NP28673 and NP28761, the CNS response rate was 64.0% (95% CI: 49.2-77.1) in patients with measurable CNS disease at baseline.…”

Section: Introductionmentioning

confidence: 97%

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<p>Time To Response In Patients With Advanced Anaplastic Lymphoma Kinase (<em>ALK</em>)-Positive Non-Small-Cell Lung Cancer (NSCLC) Receiving Alectinib In The Phase II NP28673 And NP28761 Studies</p>

Gadgeel

Shaw

Crinò

et al. 2019

LCTT

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Introduction: Alectinib is a highly selective and potent ALK inhibitor, approved for the treatment of patients with metastatic ALK+ NSCLC based on results from the Phase II global NP28673 (NCT01801111) and North American NP28761 (NCT01871805) studies. Methods: This exploratory analysis of two Phase II studies of alectinib (NP28673/ NP28761) investigated time to systemic response (TTR) and time to central nervous system (CNS) response (TTCR) in patients with previously treated advanced anaplastic lymphoma kinase fusion gene-positive (ALK+) non-small-cell lung cancer. Patients (n=225) received 600 mg oral alectinib twice daily and had scans every 6/8 weeks (NP28673/NP28761). Results: For NP28673 and NP28761, respectively: median follow-up was 21.3 months/17.0 months; most responders (72.6%/82.9%) responded by the first disease assessment; median TTR was 8 weeks (95% confidence interval [CI]: 8.00-8.14)/6 weeks (95% CI: 5.86-6.14); median TTCR in responders with measurable baseline CNS disease was 8 weeks (95% CI: 7.86-10.29)/6 weeks (95% CI: 5.71-not evaluable). Similar results were observed regardless of measurable/non-measurable disease. Discussion: These data suggest that alectinib achieves a rapid response in patients, both systemically and in the CNS.

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“…179 El análisis combinado de dos estudios fase 2 ha demostrado la efectividad de alectinib en pacientes con falla a crizotinib. [180][181][182] Las TRO fueron del 51.3% (IC95% 44-58.6), con una SLP fue de 8.3 meses (IC95% 7-11.3) y SG de 26 meses (IC95% 21.4-no estimable).…”

Section: Pregunta Clínica 55 ¿Cuáles Son Las Opciones De Tratamientounclassified

Guía de Práctica Clínica Nacional para el manejo del Cáncer de Pulmón de células no pequeñas en estadios tempranos, localmente avanzados y metastásicos

Barrón-Barrón¹,

Alba²,

Alatorre-Alexander³

et al. 2019

Salud Publica Mex

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Resumen. El cáncer de pulmón es una de las principales causas de mortalidad alrededor del mundo. Su historia natural, con la manifestación de síntomas en etapas avanzadas y el retraso en su diagnóstico hacen que una gran proporción de pacientes se diagnostiquen en estadios tardíos de la enfermedad, lo que hace muy complicado el tratamiento exitoso de la misma. De esto deriva la importancia de dar origen a recomendaciones basadas en evidencia para soportar la toma de decisiones clínicas por parte de los grupos interdisicplinarios que se encargan del manejo de este padecimiento. Objetivos. Esta Guía de Práctica Clínica (GPC) contiene recomendaciones clínicas desarrolladas de forma sistematizada para asistir la toma de decisiones de médicos especialistas, pacientes, cuidadores de pacientes y elaboradores de políticas públicas involucrados en el manejo de pacientes con cáncer de pulmón en estadios tempranos, localmente avanzados y metastásicos. Material y métodos. Este documento se desarrolló por parte de la Sociedad Mexicana de Oncología en colaboración con el Centro Nacional de Excelencia Tecnológica de México (Cenetec) a través de la dirección de integración de Guías de Práctica Clínica en cumplimiento a estándares internacionales como los descritos por el Instituto de Medicina de EUA (IOM, por sus siglas en inglés), el Instituto de Excelencia Clínica de Gran Bretaña (NICE, por sus siglas en inglés), la Red Colegiada para el Desarrollo de Guías de Escocia (SIGN, por sus siglas en inglés), la Red Internacional de Guías (G-I-N, por sus siglas en inglés); entre otros. Se integró en representación de la Sociedad Mexicana de Oncología un Grupo de Desarrollo de la Guía (GDG) de manera interdisciplinaria, considerando oncólogos médicos, cirujanos oncólogos, cirujanos de tórax, radio-oncólogos, y metodólogos con experiencia en revisiones sistemáticas de la literatura y guías de práctica clínica. Resultados. Se consensuaron 62 preguntas cllínicas que abarcaron lo establecido previamente por el GDG en el documento de alcances de la Guía. Se identificó la evidencia científica que responde a cada una de estas preguntas clínicas y se evaluó críticamente la misma, antes de ser incorporada en el cuerpo de evidencia de la Guía. El GDG acordó mediante la técnica de consenso formal de expertos Panel Delphi la redacción final de las recomendaciones clínicas. Conclusión. Esta Guía de Práctica Clínica pretende proveer recomendaciones clínicas para el manejo de los distintos estadios de la enfermedad y que asistan en el proceso de toma de decisiones compartida. El GDG espera que esta guía contribuya a mejorar la calidad de la atención clínica en las pacientes con cáncer de pulmón de células no pequeñas.

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Pooled Systemic Efficacy and Safety Data from the Pivotal Phase II Studies (NP28673 and NP28761) of Alectinib in ALK -positive Non-Small Cell Lung Cancer

Abstract: This pooled data analysis confirmed the robust systemic efficacy of alectinib in ALK-positive NSCLC with a durable response rate. Alectinib also had an acceptable safety profile with a longer duration of follow-up.

Cited by 75 publications

References 23 publications

Real-World Treatment Patterns and Progression-Free Survival Associated with Anaplastic Lymphoma Kinase (ALK) Tyrosine Kinase Inhibitor Therapies for ALK+ Non-Small Cell Lung Cancer

Real-World Treatment Patterns and Progression-Free Survival Associated with Anaplastic Lymphoma Kinase (ALK) Tyrosine Kinase Inhibitor Therapies for ALK+ Non-Small Cell Lung Cancer

<p>Time To Response In Patients With Advanced Anaplastic Lymphoma Kinase (<em>ALK</em>)-Positive Non-Small-Cell Lung Cancer (NSCLC) Receiving Alectinib In The Phase II NP28673 And NP28761 Studies</p>

Guía de Práctica Clínica Nacional para el manejo del Cáncer de Pulmón de células no pequeñas en estadios tempranos, localmente avanzados y metastásicos

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