Pooled overall survival and safety data from the pivotal phase II studies (NP28673 and NP28761) of alectinib in ALK-positive non-small-cell lung cancer

Sai Hong Ignatius Ou, Shirish M. Gadgeel, Fabrice Barlesi, James Chih Hsin Yang, Luigi De Petris, Dong Wan Kim, Ramaswamy Govindan, Anne Marie Dingemans, Lucio Crino, Hervé Léna, Sanjay Popat, Jin Seok Ahn, Eric Dansin, Emmanuel Mitry, Barbara Müller, Walter Bordogna, Bogdana Balas, Peter N. Morcos, Alice T. Shaw

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Abstract

Objectives: A pooled analysis of two open-label phase II studies of alectinib (NP28673 [NCT01801111] and NP28761 [NCT01871805]) demonstrated clinical activity in patients with advanced, anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer (NSCLC) previously treated with crizotinib. Longer-term and final pooled analyses of overall survival (OS) and safety data from the two studies are presented here. Patients and methods: The pooled population totaled 225 patients (NP28673: n = 138, NP28761: n = 87) who received 600 mg oral alectinib twice daily until disease progression, death, or withdrawal. OS was defined as the time from date of first treatment to date of death, regardless of cause. OS was estimated using Kaplan–Meier methodology, with 95% confidence intervals (CIs) determined using the Brookmeyer–Crowley method. Safety was assessed through adverse event (AE) reporting. Results: Baseline characteristics were generally comparable between the studies. At final data cutoff (October 27, 2017 [NP28673], October 12, 2017 [NP28761]; median pooled follow-up time, ∼21 months), 53.3% of patients had died, 39.1% were alive and in follow-up, and 7.6% had withdrawn consent or were lost to follow-up. Alectinib demonstrated a median OS of 29.1 months (95% CI 21.3–39.0). No new or unexpected safety findings were observed. The most common all-grade AEs included constipation (39.1%), fatigue (35.1%), peripheral edema (28.4%), myalgia (26.2%), and nausea (24.0%). Conclusion: Updated results from this pooled analysis further demonstrate that alectinib has robust clinical activity and a manageable safety profile in patients with advanced, ALK+ NSCLC pretreated with crizotinib.

Original languageEnglish
Pages (from-to)22-27
Number of pages6
JournalLung Cancer
Volume139
DOIs
StatePublished - Jan 2020

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Non-Small Cell Lung Carcinoma
Safety
Survival
Confidence Intervals
Lost to Follow-Up
Myalgia
Constipation
Survival Analysis
Nausea
Fatigue
Disease Progression
Cause of Death
Edema
CH5424802
Population
crizotinib
Therapeutics

Keywords

  • ALK+
  • Alectinib
  • NSCLC
  • Overall survival
  • Pooled analysis
  • Safety

Cite this

Ou, Sai Hong Ignatius ; Gadgeel, Shirish M. ; Barlesi, Fabrice ; Yang, James Chih Hsin ; De Petris, Luigi ; Kim, Dong Wan ; Govindan, Ramaswamy ; Dingemans, Anne Marie ; Crino, Lucio ; Léna, Hervé ; Popat, Sanjay ; Ahn, Jin Seok ; Dansin, Eric ; Mitry, Emmanuel ; Müller, Barbara ; Bordogna, Walter ; Balas, Bogdana ; Morcos, Peter N. ; Shaw, Alice T. / Pooled overall survival and safety data from the pivotal phase II studies (NP28673 and NP28761) of alectinib in ALK-positive non-small-cell lung cancer. In: Lung Cancer. 2020 ; Vol. 139. pp. 22-27.
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title = "Pooled overall survival and safety data from the pivotal phase II studies (NP28673 and NP28761) of alectinib in ALK-positive non-small-cell lung cancer",
abstract = "Objectives: A pooled analysis of two open-label phase II studies of alectinib (NP28673 [NCT01801111] and NP28761 [NCT01871805]) demonstrated clinical activity in patients with advanced, anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer (NSCLC) previously treated with crizotinib. Longer-term and final pooled analyses of overall survival (OS) and safety data from the two studies are presented here. Patients and methods: The pooled population totaled 225 patients (NP28673: n = 138, NP28761: n = 87) who received 600 mg oral alectinib twice daily until disease progression, death, or withdrawal. OS was defined as the time from date of first treatment to date of death, regardless of cause. OS was estimated using Kaplan–Meier methodology, with 95{\%} confidence intervals (CIs) determined using the Brookmeyer–Crowley method. Safety was assessed through adverse event (AE) reporting. Results: Baseline characteristics were generally comparable between the studies. At final data cutoff (October 27, 2017 [NP28673], October 12, 2017 [NP28761]; median pooled follow-up time, ∼21 months), 53.3{\%} of patients had died, 39.1{\%} were alive and in follow-up, and 7.6{\%} had withdrawn consent or were lost to follow-up. Alectinib demonstrated a median OS of 29.1 months (95{\%} CI 21.3–39.0). No new or unexpected safety findings were observed. The most common all-grade AEs included constipation (39.1{\%}), fatigue (35.1{\%}), peripheral edema (28.4{\%}), myalgia (26.2{\%}), and nausea (24.0{\%}). Conclusion: Updated results from this pooled analysis further demonstrate that alectinib has robust clinical activity and a manageable safety profile in patients with advanced, ALK+ NSCLC pretreated with crizotinib.",
keywords = "ALK+, Alectinib, NSCLC, Overall survival, Pooled analysis, Safety",
author = "Ou, {Sai Hong Ignatius} and Gadgeel, {Shirish M.} and Fabrice Barlesi and Yang, {James Chih Hsin} and {De Petris}, Luigi and Kim, {Dong Wan} and Ramaswamy Govindan and Dingemans, {Anne Marie} and Lucio Crino and Herv{\'e} L{\'e}na and Sanjay Popat and Ahn, {Jin Seok} and Eric Dansin and Emmanuel Mitry and Barbara M{\"u}ller and Walter Bordogna and Bogdana Balas and Morcos, {Peter N.} and Shaw, {Alice T.}",
year = "2020",
month = "1",
doi = "10.1016/j.lungcan.2019.10.015",
language = "English",
volume = "139",
pages = "22--27",
journal = "Lung Cancer",
issn = "0169-5002",
publisher = "Elsevier Ireland Ltd",

}

Ou, SHI, Gadgeel, SM, Barlesi, F, Yang, JCH, De Petris, L, Kim, DW, Govindan, R, Dingemans, AM, Crino, L, Léna, H, Popat, S, Ahn, JS, Dansin, E, Mitry, E, Müller, B, Bordogna, W, Balas, B, Morcos, PN & Shaw, AT 2020, 'Pooled overall survival and safety data from the pivotal phase II studies (NP28673 and NP28761) of alectinib in ALK-positive non-small-cell lung cancer', Lung Cancer, vol. 139, pp. 22-27. https://doi.org/10.1016/j.lungcan.2019.10.015

Pooled overall survival and safety data from the pivotal phase II studies (NP28673 and NP28761) of alectinib in ALK-positive non-small-cell lung cancer. / Ou, Sai Hong Ignatius; Gadgeel, Shirish M.; Barlesi, Fabrice; Yang, James Chih Hsin; De Petris, Luigi; Kim, Dong Wan; Govindan, Ramaswamy; Dingemans, Anne Marie; Crino, Lucio; Léna, Hervé; Popat, Sanjay; Ahn, Jin Seok; Dansin, Eric; Mitry, Emmanuel; Müller, Barbara; Bordogna, Walter; Balas, Bogdana; Morcos, Peter N.; Shaw, Alice T.

In: Lung Cancer, Vol. 139, 01.2020, p. 22-27.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Pooled overall survival and safety data from the pivotal phase II studies (NP28673 and NP28761) of alectinib in ALK-positive non-small-cell lung cancer

AU - Ou, Sai Hong Ignatius

AU - Gadgeel, Shirish M.

AU - Barlesi, Fabrice

AU - Yang, James Chih Hsin

AU - De Petris, Luigi

AU - Kim, Dong Wan

AU - Govindan, Ramaswamy

AU - Dingemans, Anne Marie

AU - Crino, Lucio

AU - Léna, Hervé

AU - Popat, Sanjay

AU - Ahn, Jin Seok

AU - Dansin, Eric

AU - Mitry, Emmanuel

AU - Müller, Barbara

AU - Bordogna, Walter

AU - Balas, Bogdana

AU - Morcos, Peter N.

AU - Shaw, Alice T.

PY - 2020/1

Y1 - 2020/1

N2 - Objectives: A pooled analysis of two open-label phase II studies of alectinib (NP28673 [NCT01801111] and NP28761 [NCT01871805]) demonstrated clinical activity in patients with advanced, anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer (NSCLC) previously treated with crizotinib. Longer-term and final pooled analyses of overall survival (OS) and safety data from the two studies are presented here. Patients and methods: The pooled population totaled 225 patients (NP28673: n = 138, NP28761: n = 87) who received 600 mg oral alectinib twice daily until disease progression, death, or withdrawal. OS was defined as the time from date of first treatment to date of death, regardless of cause. OS was estimated using Kaplan–Meier methodology, with 95% confidence intervals (CIs) determined using the Brookmeyer–Crowley method. Safety was assessed through adverse event (AE) reporting. Results: Baseline characteristics were generally comparable between the studies. At final data cutoff (October 27, 2017 [NP28673], October 12, 2017 [NP28761]; median pooled follow-up time, ∼21 months), 53.3% of patients had died, 39.1% were alive and in follow-up, and 7.6% had withdrawn consent or were lost to follow-up. Alectinib demonstrated a median OS of 29.1 months (95% CI 21.3–39.0). No new or unexpected safety findings were observed. The most common all-grade AEs included constipation (39.1%), fatigue (35.1%), peripheral edema (28.4%), myalgia (26.2%), and nausea (24.0%). Conclusion: Updated results from this pooled analysis further demonstrate that alectinib has robust clinical activity and a manageable safety profile in patients with advanced, ALK+ NSCLC pretreated with crizotinib.

AB - Objectives: A pooled analysis of two open-label phase II studies of alectinib (NP28673 [NCT01801111] and NP28761 [NCT01871805]) demonstrated clinical activity in patients with advanced, anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer (NSCLC) previously treated with crizotinib. Longer-term and final pooled analyses of overall survival (OS) and safety data from the two studies are presented here. Patients and methods: The pooled population totaled 225 patients (NP28673: n = 138, NP28761: n = 87) who received 600 mg oral alectinib twice daily until disease progression, death, or withdrawal. OS was defined as the time from date of first treatment to date of death, regardless of cause. OS was estimated using Kaplan–Meier methodology, with 95% confidence intervals (CIs) determined using the Brookmeyer–Crowley method. Safety was assessed through adverse event (AE) reporting. Results: Baseline characteristics were generally comparable between the studies. At final data cutoff (October 27, 2017 [NP28673], October 12, 2017 [NP28761]; median pooled follow-up time, ∼21 months), 53.3% of patients had died, 39.1% were alive and in follow-up, and 7.6% had withdrawn consent or were lost to follow-up. Alectinib demonstrated a median OS of 29.1 months (95% CI 21.3–39.0). No new or unexpected safety findings were observed. The most common all-grade AEs included constipation (39.1%), fatigue (35.1%), peripheral edema (28.4%), myalgia (26.2%), and nausea (24.0%). Conclusion: Updated results from this pooled analysis further demonstrate that alectinib has robust clinical activity and a manageable safety profile in patients with advanced, ALK+ NSCLC pretreated with crizotinib.

KW - ALK+

KW - Alectinib

KW - NSCLC

KW - Overall survival

KW - Pooled analysis

KW - Safety

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U2 - 10.1016/j.lungcan.2019.10.015

DO - 10.1016/j.lungcan.2019.10.015

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