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

Research output: Contribution to journalArticleAcademicpeer-review

21 Citations (Scopus)
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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 languageEnglish
Pages (from-to)38-42
Number of pages5
JournalBritish Journal of Cancer
Volume118
Issue number1
DOIs
Publication statusPublished - 16 Nov 2017
Externally publishedYes

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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