Cumulative incidence rates for CNS and non-CNS progression in two phase II studies of alectinib in ALK-positive NSCLC

Shirish Gadgeel; Alice T. Shaw; Fabrice Barlesi; Lucio Crinò; James Chih Hsin Yang; Anne Marie C. Dingemans; Dong Wan Kim; Filippo De Marinis; Mathias Schulz; Shiyao Liu; Ravindra Gupta; Ahmed Kotb; Sai Hong Ignatius Ou

doi:10.1038/bjc.2017.395

Cumulative incidence rates for CNS and non-CNS progression in two phase II studies of alectinib in ALK-positive NSCLC

Shirish Gadgeel^*
, Alice T. Shaw
, Fabrice Barlesi
, Lucio Crinò
, James Chih Hsin Yang
, Anne Marie C. Dingemans
, Dong Wan Kim
, Filippo De Marinis
, Mathias Schulz
, Shiyao Liu
, Ravindra Gupta
, Ahmed Kotb
, Sai Hong Ignatius Ou

^*Corresponding author for this work

University of Michigan, Ann Arbor
Massachusetts General Hospital
Aix-Marseille Université
IRCCS Istituto scientifico romagnolo per lo studio e la cura dei tumori - Meldola (FC)
National Taiwan University
Seoul National University
IRCCS Istituto Europeo di Oncologia - Milano
Genentech Incorporated
F. Hoffmann-La Roche AG
University of California at Irvine
Maastricht University

Research output: Contribution to journal › Article › Academic › peer-review

23 Citations (Scopus)

37 Downloads (Pure)

Abstract

Background:
We evaluated the cumulative incidence rate (CIR) of central nervous system (CNS) and non-CNS progression in alectinib-treated patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) to determine the extent to which alectinib may treat or control CNS disease.

Methods:
Patients with crizotinib-pretreated locally advanced or metastatic disease received alectinib 600 mg orally twice daily in two phase II trials. All patients underwent baseline imaging and regular centrally reviewed scans.

Results:
At 24 months, the CIR for CNS progression was lower in patients without vs with baseline CNS metastases (8.0 vs 43.9%). Patients with baseline CNS disease and prior radiotherapy had a higher CIR of CNS progression than radiotherapy-naive patients (50.5 vs 27.4%) and a lower CIR of non-CNS progression (25.8 vs 42.5%). Adverse events leading to withdrawal occurred in 5.9% and 6.7% of patients with and without baseline CNS metastases, respectively.

Conclusions:
This analysis indicates a potential role for alectinib in controlling and preventing CNS metastases.

Original language	English
Pages (from-to)	38-42
Number of pages	5
Journal	British Journal of Cancer
Volume	118
Issue number	1
DOIs	https://doi.org/10.1038/bjc.2017.395
Publication status	Published - 16 Nov 2017
Externally published	Yes

Bibliographical note

Funding Information:
SG has participated in advisory boards for Genentech/Roche, Ariad, Pfizer, and Bristol-Myers Squibb, and received honoraria for non-branded presentations for Genentech/Roche; ATS has participated in advisory boards for Pfizer, Novartis, Roche/Genentech, Ariad, Blueprint Medicines, Loxo, and EMD Serono, and received honoraria for non-branded presentations for Pfizer, Novartis, Genentech/Roche, Ignyta, Taiho and Foundation Medicine; FB has participated in advisory boards for Genentech/Roche, Novartis, and Pfizer, and received honoraria for non-branded presentations for Genentech/Roche and Novartis; LC has received honoraria from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, and Pfizer; JC-HY has participated in compensated advisory boards for Boehringer Ingelheim, Eli Lilly, Bayer, Roche/Genen-tech/Chugai, Astellas, MSD, Merck Serono, Pfizer, Novartis, Clovis Oncology, Celgene, Merrimack, Yuhan Pharmaceuticals, Bristol-Myers Squibb, and Ono Pharmaceutical, and in an uncompensated advisory board for AstraZeneca; A-MCD has participated in advisory boards for Genentech/Roche, Pfizer, Eli Lilly, Clovis, and MSD, and received honoraria for non-branded presentations for Genentech/Roche and AstraZeneca (paid to her institute); D-WK has no conflict of interest to disclose; FdM has participated in advisory boards for Genentech/Roche, Boehringer, and Novartis, and received honoraria for non-branded presentations from Genentech/Roche, AstraZeneca, Bristol-Mayer Squibb, and Pfizer; MS is an employee of Genentech and owns Roche stocks; SL and RG are employees of Genentech and own shares in the company; AK is an employee of F. Hoffmann-La Roche Ltd and owns shares in the company; S-HIO has acted in a consulting or advisory role to ARIAD, AstraZeneca, Boehringer Ingelheim, Novartis, and Roche, and participated in Speaker Bureaus for AstraZeneca, Boehringer Ingelheim, and Roche/Genentech.

Funding Information:
We thank the patients, their families, and the participating centres for both studies. Third-party medical writing assistance, under the direction of the authors, was provided by Fiona Fernando of Gardiner-Caldwell Communications and funded by F. Hoffmann-La Roche Ltd.

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SDG 3 Good Health and Well-being

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Cite this

Gadgeel, S., Shaw, A. T., Barlesi, F., Crinò, L., Yang, J. C. H., Dingemans, A. M. C., Kim, D. W., De Marinis, F., Schulz, M., Liu, S., Gupta, R., Kotb, A., & Ou, S. H. I. (2017). Cumulative incidence rates for CNS and non-CNS progression in two phase II studies of alectinib in ALK-positive NSCLC. British Journal of Cancer, 118(1), 38-42. https://doi.org/10.1038/bjc.2017.395

@article{8189fd92c9954ad68acb05a5496a966c,

title = "Cumulative incidence rates for CNS and non-CNS progression in two phase II studies of alectinib in ALK-positive NSCLC",

abstract = "Background: We evaluated the cumulative incidence rate (CIR) of central nervous system (CNS) and non-CNS progression in alectinib-treated patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) to determine the extent to which alectinib may treat or control CNS disease. Methods: Patients with crizotinib-pretreated locally advanced or metastatic disease received alectinib 600 mg orally twice daily in two phase II trials. All patients underwent baseline imaging and regular centrally reviewed scans. Results: At 24 months, the CIR for CNS progression was lower in patients without vs with baseline CNS metastases (8.0 vs 43.9\%). Patients with baseline CNS disease and prior radiotherapy had a higher CIR of CNS progression than radiotherapy-naive patients (50.5 vs 27.4\%) and a lower CIR of non-CNS progression (25.8 vs 42.5\%). Adverse events leading to withdrawal occurred in 5.9\% and 6.7\% of patients with and without baseline CNS metastases, respectively. Conclusions: This analysis indicates a potential role for alectinib in controlling and preventing CNS metastases.",

author = "Shirish Gadgeel and Shaw, \{Alice T.\} and Fabrice Barlesi and Lucio Crin{\`o} and Yang, \{James Chih Hsin\} and Dingemans, \{Anne Marie C.\} and Kim, \{Dong Wan\} and \{De Marinis\}, Filippo and Mathias Schulz and Shiyao Liu and Ravindra Gupta and Ahmed Kotb and Ou, \{Sai Hong Ignatius\}",

note = "Funding Information: SG has participated in advisory boards for Genentech/Roche, Ariad, Pfizer, and Bristol-Myers Squibb, and received honoraria for non-branded presentations for Genentech/Roche; ATS has participated in advisory boards for Pfizer, Novartis, Roche/Genentech, Ariad, Blueprint Medicines, Loxo, and EMD Serono, and received honoraria for non-branded presentations for Pfizer, Novartis, Genentech/Roche, Ignyta, Taiho and Foundation Medicine; FB has participated in advisory boards for Genentech/Roche, Novartis, and Pfizer, and received honoraria for non-branded presentations for Genentech/Roche and Novartis; LC has received honoraria from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, and Pfizer; JC-HY has participated in compensated advisory boards for Boehringer Ingelheim, Eli Lilly, Bayer, Roche/Genen-tech/Chugai, Astellas, MSD, Merck Serono, Pfizer, Novartis, Clovis Oncology, Celgene, Merrimack, Yuhan Pharmaceuticals, Bristol-Myers Squibb, and Ono Pharmaceutical, and in an uncompensated advisory board for AstraZeneca; A-MCD has participated in advisory boards for Genentech/Roche, Pfizer, Eli Lilly, Clovis, and MSD, and received honoraria for non-branded presentations for Genentech/Roche and AstraZeneca (paid to her institute); D-WK has no conflict of interest to disclose; FdM has participated in advisory boards for Genentech/Roche, Boehringer, and Novartis, and received honoraria for non-branded presentations from Genentech/Roche, AstraZeneca, Bristol-Mayer Squibb, and Pfizer; MS is an employee of Genentech and owns Roche stocks; SL and RG are employees of Genentech and own shares in the company; AK is an employee of F. Hoffmann-La Roche Ltd and owns shares in the company; S-HIO has acted in a consulting or advisory role to ARIAD, AstraZeneca, Boehringer Ingelheim, Novartis, and Roche, and participated in Speaker Bureaus for AstraZeneca, Boehringer Ingelheim, and Roche/Genentech. Funding Information: We thank the patients, their families, and the participating centres for both studies. Third-party medical writing assistance, under the direction of the authors, was provided by Fiona Fernando of Gardiner-Caldwell Communications and funded by F. Hoffmann-La Roche Ltd.",

year = "2017",

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doi = "10.1038/bjc.2017.395",

language = "English",

volume = "118",

pages = "38--42",

journal = "British Journal of Cancer",

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TY - JOUR

T1 - Cumulative incidence rates for CNS and non-CNS progression in two phase II studies of alectinib in ALK-positive NSCLC

AU - Gadgeel, Shirish

AU - Shaw, Alice T.

AU - Barlesi, Fabrice

AU - Crinò, Lucio

AU - Yang, James Chih Hsin

AU - Dingemans, Anne Marie C.

AU - Kim, Dong Wan

AU - De Marinis, Filippo

AU - Schulz, Mathias

AU - Liu, Shiyao

AU - Gupta, Ravindra

AU - Kotb, Ahmed

AU - Ou, Sai Hong Ignatius

N1 - Funding Information: SG has participated in advisory boards for Genentech/Roche, Ariad, Pfizer, and Bristol-Myers Squibb, and received honoraria for non-branded presentations for Genentech/Roche; ATS has participated in advisory boards for Pfizer, Novartis, Roche/Genentech, Ariad, Blueprint Medicines, Loxo, and EMD Serono, and received honoraria for non-branded presentations for Pfizer, Novartis, Genentech/Roche, Ignyta, Taiho and Foundation Medicine; FB has participated in advisory boards for Genentech/Roche, Novartis, and Pfizer, and received honoraria for non-branded presentations for Genentech/Roche and Novartis; LC has received honoraria from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, and Pfizer; JC-HY has participated in compensated advisory boards for Boehringer Ingelheim, Eli Lilly, Bayer, Roche/Genen-tech/Chugai, Astellas, MSD, Merck Serono, Pfizer, Novartis, Clovis Oncology, Celgene, Merrimack, Yuhan Pharmaceuticals, Bristol-Myers Squibb, and Ono Pharmaceutical, and in an uncompensated advisory board for AstraZeneca; A-MCD has participated in advisory boards for Genentech/Roche, Pfizer, Eli Lilly, Clovis, and MSD, and received honoraria for non-branded presentations for Genentech/Roche and AstraZeneca (paid to her institute); D-WK has no conflict of interest to disclose; FdM has participated in advisory boards for Genentech/Roche, Boehringer, and Novartis, and received honoraria for non-branded presentations from Genentech/Roche, AstraZeneca, Bristol-Mayer Squibb, and Pfizer; MS is an employee of Genentech and owns Roche stocks; SL and RG are employees of Genentech and own shares in the company; AK is an employee of F. Hoffmann-La Roche Ltd and owns shares in the company; S-HIO has acted in a consulting or advisory role to ARIAD, AstraZeneca, Boehringer Ingelheim, Novartis, and Roche, and participated in Speaker Bureaus for AstraZeneca, Boehringer Ingelheim, and Roche/Genentech. Funding Information: We thank the patients, their families, and the participating centres for both studies. Third-party medical writing assistance, under the direction of the authors, was provided by Fiona Fernando of Gardiner-Caldwell Communications and funded by F. Hoffmann-La Roche Ltd.

PY - 2017/11/16

Y1 - 2017/11/16

N2 - Background: We evaluated the cumulative incidence rate (CIR) of central nervous system (CNS) and non-CNS progression in alectinib-treated patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) to determine the extent to which alectinib may treat or control CNS disease. Methods: Patients with crizotinib-pretreated locally advanced or metastatic disease received alectinib 600 mg orally twice daily in two phase II trials. All patients underwent baseline imaging and regular centrally reviewed scans. Results: At 24 months, the CIR for CNS progression was lower in patients without vs with baseline CNS metastases (8.0 vs 43.9%). Patients with baseline CNS disease and prior radiotherapy had a higher CIR of CNS progression than radiotherapy-naive patients (50.5 vs 27.4%) and a lower CIR of non-CNS progression (25.8 vs 42.5%). Adverse events leading to withdrawal occurred in 5.9% and 6.7% of patients with and without baseline CNS metastases, respectively. Conclusions: This analysis indicates a potential role for alectinib in controlling and preventing CNS metastases.

AB - Background: We evaluated the cumulative incidence rate (CIR) of central nervous system (CNS) and non-CNS progression in alectinib-treated patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) to determine the extent to which alectinib may treat or control CNS disease. Methods: Patients with crizotinib-pretreated locally advanced or metastatic disease received alectinib 600 mg orally twice daily in two phase II trials. All patients underwent baseline imaging and regular centrally reviewed scans. Results: At 24 months, the CIR for CNS progression was lower in patients without vs with baseline CNS metastases (8.0 vs 43.9%). Patients with baseline CNS disease and prior radiotherapy had a higher CIR of CNS progression than radiotherapy-naive patients (50.5 vs 27.4%) and a lower CIR of non-CNS progression (25.8 vs 42.5%). Adverse events leading to withdrawal occurred in 5.9% and 6.7% of patients with and without baseline CNS metastases, respectively. Conclusions: This analysis indicates a potential role for alectinib in controlling and preventing CNS metastases.

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DO - 10.1038/bjc.2017.395

M3 - Article

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AN - SCOPUS:85040316540

SN - 0007-0920

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EP - 42

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 1

ER -

Cumulative incidence rates for CNS and non-CNS progression in two phase II studies of alectinib in ALK-positive NSCLC

Abstract

Bibliographical note

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