Reactions 1680, p99 - 2 Dec 2017
ALK and KRAS mutations leading to acquired
crizotinib resistance: 12 case reports
In a study of 20 patients, 12 patients (eight women and four
men) aged between 40
81 years were described, who
developed anaplastic lymphoma kinase (ALK; n=5) and
Kirsten rat sarcoma (KRAS; n=10) gene mutations leading to
acquired crizotinib resistance [routes and dosages not stated].
The patients had a history of advanced ALK-positive non
small cell lung cancer (NSCLC) and started receiving treatment
with tyrosine kinase inhibitor (TKI), crizotinib. The patients
experienced disease progression at different site like lymph
node (n=3), brain (n=9), liver (n=2), lung (n=2) and pleura
(n=2). Subsequent investigations revealed development of
ALK and KRAS gene mutations which conferred the resistance.
The patients started receiving treatment with chemotherapy
(one patient), brigatinib (n=9) and ceritinib (one patient). The
disease was stable in three of the 12 patients. Disease
progression was observed in another three patients [not all
Author comment: "To our knowledge, this is the first
report to evaluate the acquired resistance to ALK-TKIs using
cfDNA in a cohort of crizotinib-resistant NSCLC patients."
Bordi P, et al. Detection of ALK and KRAS Mutations in Circulating Tumor DNA
of Patients With Advanced ALK-Positive NSCLC With Disease Progression
During Crizotinib Treatment. Clinical Lung Cancer 18: 692-697, No. 6, Nov 2017.
Available from: URL: http://doi.org/10.1016/j.cllc.2017.04.013 - Italy
Reactions 2 Dec 2017 No. 16800114-9954/17/1680-0001/$14.95 Adis © 2017 Springer International Publishing AG. All rights reserved