| Reference | 1. Future Oncol. 2017 Feb;13(4):321-335. doi: 10.2217/fon-2016-0386. Epub 2016 Oct
26.
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Alectinib for treatment of ALK-positive non-small-cell lung cancer.
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Avrillon V(1), Pérol M(1).
<br>
Author information: <br>
(1)Department of Medical Oncology, Léon Bérard Cancer Center, Lyon, France.
<br>
Alectinib is a highly selective second-generation ALK inhibitor that is active
against most crizotinib ALK resistance mutations, with a good penetration in CNS
and a good safety profile. Thanks to the positive results of Phase II trials,
alectinib was approved in Japan and by the US FDA for ALK-positive non-small-cell
lung cancer (NSCLC) patients pretreated with crizotinib. Recently, the Phase III
J-ALEX study demonstrated superiority of alectinib over crizotinib in crizotinib
naive ALK-positive NSCLC, with an impressive improvement of progression-free
survival. From the results and those expected of Phase III ALEX study, alectinib
might become the frontline treatment of ALK-positive NSCLC. This article
summarizes the therapeutic options in ALK-positive advanced NSCLC, and the
chemical, pharmacodynamics, pharmacokinetics, metabolism and clinical efficacy of
alectinib.
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2. Expert Rev Clin Pharmacol. 2016 Aug;9(8):1005-13. doi:
10.1080/17512433.2016.1195262. Epub 2016 Jun 21.
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Alectinib for ALK-positive non-small-cell lung cancer.
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Rossi A(1).
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Author information: <br>
(1)a Division of Medical Oncology , /S.G. Moscati/ Hospital , Avellino , Italy.
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INTRODUCTION: Anaplastic lymphoma kinase (ALK) rearrangements are present in
about 5% of advanced non-small-cell lung cancer (NSCLC) patients. Despite the
initial response, after a median of 1-2 years, ALK-positive patients developed an
acquired resistance to the ALK-inhibitor crizotinib. Among the most promising
second-generation ALK-inhibitors, alectinib is being investigated in
crizotinib-naïve and -resistant ALK-positive NSCLC patients.
AREAS COVERED: The current state-of-the-art of ALK-inhibitors treatment, and in
particular the role of alectinib in this setting, is reviewed and discussed. A
structured search of bibliographic databases for peer-reviewed research
literature and of main meetings using a focused review question was undertaken.
Expert commentary: Alectinib reports promising results with a good safety
profile, becoming a potentially very important option for ALK-translocated NSCLC
patients. The preliminary results from the J-ALEX phase III randomized trial
performed in ALK-rearranged NSCLC Japanese patients showed a better activity and
tolerability of alectinib versus crizotinib.
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3. Drugs. 2015 Jan;75(1):75-82. doi: 10.1007/s40265-014-0329-y.
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Alectinib: a review of its use in advanced ALK-rearranged non-small cell lung
cancer.
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McKeage K(1).
<br>
Author information: <br>
(1)Springer, Private Bag 65901, Mairangi Bay 0754, Auckland, New Zealand,
[email protected].
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Erratum in<br>
Drugs. 2015 Feb;75(2):241.
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Alectinib (Alecensa(®)) is a second-generation, orally active, potent and highly
selective inhibitor of anaplastic lymphoma kinase (ALK). Alectinib is approved
for the treatment of ALK fusion-gene positive, unresectable, advanced or
recurrent non-small cell lung cancer (NSCLC) in Japan, where it has been given
orphan drug designation. Approval was based on a phase 1-2 study in ALK
inhibitor-naive patients with ALK-rearranged advanced NSCLC who received
twice-daily alectinib 300 mg. In the phase 2 portion, 93.5 % of patients achieved
an objective response. Treatment response was rapid, with a partial response
achieved in two-thirds of patients within 3 weeks (cycle 1). Patient follow-up is
ongoing, and after approximately 2 years, 19.6 % of patients had achieved a
complete response, and the 2-year progression-free survival rate is 76 %. During
treatment with alectinib (median follow-up approximately 8 months), there was no
progression of CNS lesions among patients with known CNS metastases at baseline
(although prior radiation therapy may have confounded results). In preclinical
models, alectinib was active against most ALK fusion-gene mutations related to
crizotinib resistance, and preliminary results from clinical trials indicate
efficacy in crizotinib-refractory NSCLC. Alectinib was generally well tolerated
in clinical trials, and there were no treatment-related grade 4 adverse events or
deaths. The most common grade 3 treatment-related adverse events were decreased
neutrophil counts and increased creatinine phosphokinase. While more data are
needed to confirm the efficacy of alectinib and to evaluate its activity in
crizotinib-resistant disease, the drug provides a very promising option for the
treatment of ALK-rearranged advanced NSCLC.
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