Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2015 Feb;10(2):232-6.
doi: 10.1097/JTO.0000000000000455.

Alectinib salvages CNS relapses in ALK-positive lung cancer patients previously treated with crizotinib and ceritinib

Justin F Gainor  1 , Carol A Sherman, Kathryn Willoughby, Jennifer Logan, Elizabeth Kennedy, Priscilla K Brastianos, Andrew S Chi, Alice T Shaw
Affiliations
Case Reports

Alectinib salvages CNS relapses in ALK-positive lung cancer patients previously treated with crizotinib and ceritinib

Justin F Gainor et al. J Thorac Oncol. 2015 Feb.

Abstract

Background: Leptomeningeal metastases (LM) are an increasingly frequent and devastating complication of anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC). Currently, the optimal management of LM in ALK-positive patients remains poorly understood as these patients have been routinely excluded from clinical trials.

Methods: We describe four ALK-positive patients with LM who were treated with the next-generation ALK inhibitor alectinib through single-patient, compassionate use protocols at two institutions. All patients had previously been treated with both FDA-approved ALK inhibitors--crizotinib and ceritinib. Patients received alectinib at a starting dose of 600 mg twice daily.

Results: Four ALK-positive NSCLC patients with symptomatic leptomeningeal disease were identified. Three of four patients experienced significant clinical and radiographic improvements in LM upon treatment with alectinib. A fourth patient had stable intracranial disease for 4 months before eventual systemic disease progression. Overall, alectinib was well tolerated. One patient required dose reduction due to grade 2 hyperbilirubinemia.

Conclusions: Alectinib is active in ALK-rearranged NSCLC patients with LM, including in patients previously treated with crizotinib and ceritinib. Additional prospective studies of alectinib in ALK-positive patients with LM are warranted.

PubMed Disclaimer

Figures

Figure 1
Figure 1
T1, post-gadolinium magnetic resonance images (MRI) depicting near complete resolution of leptomeningeal enhancement in a patient treated with alectinib. A) Before treatment with alectinib (blue arrows = abnormal leptomeningeal enhancement). B) Two months after initiation of treatment with alectinib.
Figure 2
Figure 2
Regression of a nodular leptomeningeal metastasis in an ALK-positive patient treated with alectinib. Sagittal, T1 post-gadolinium magnetic resonance images A) prior to treatment with alectinib (blue arrows = abnormal, nodular leptomeningeal enhancement) and B) six weeks after starting alectinib.
Figure 3
Figure 3
Marked regression in brain parenchymal metastases in a 46 year-old, ALK-positive lung cancer patient treated with alectinib. This patient had previously received both crizotinib and ceritinib, relapsing in the central nervous system after each agent. Axial, T1 post-gadolinium magnetic resonance images A) prior to alectinib and B) on alectinib.
See this image and copyright information in PMC

References

    1. Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010;363(18):1693–1703. - PMC - PubMed
    1. Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 2007;448(7153):561–566. - PubMed
    1. Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013;368(25):2385–2394. - PubMed
    1. Mok T, Kim D, Wu Y, et al. First-line crizotinib versus pemetrexed-cisplatin or pemetrexed-carboplatin in patients (pts) with advanced ALK-positive non-squamous non-small cell lung cancer (NSCLC): results of a phase III study (PROFILE 1014) J Clin Oncol. 2014;32:5s. (suppl; abstr 8002)
    1. Kim D-W, Mehra R, Tan DS, et al. Ceritinib in advanced anaplastic lymphoma kinase (ALK)-rearranged (ALK+) non-small cell lung cancer (NSCLC): Results of the ASCEND-1 trial. J Clin Oncol. 2014;32:5S. (suppl; abstr 8003)

Publication types

MeSH terms