Oncotarget

Case Reports:

A case of ALK-rearranged non–small cell lung cancer that responded to ceritinib after development of resistance to alectinib

Yosuke Makuuchi _, Hidetoshi Hayashi, Koji Haratani, Junko Tanizaki, Kaoru Tanaka, Masayuki Takeda, Kazuko Sakai, Shigeki Shimizu, Akihiko Ito, Kazuto Nishio and Kazuhiko Nakagawa

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Oncotarget. 2018; 9:23315-23319. https://doi.org/10.18632/oncotarget.25143

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Abstract

Yosuke Makuuchi1,2, Hidetoshi Hayashi1, Koji Haratani1, Junko Tanizaki1, Kaoru Tanaka1, Masayuki Takeda1, Kazuko Sakai3, Shigeki Shimizu4, Akihiko Ito4, Kazuto Nishio3 and Kazuhiko Nakagawa1

1Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka 589-8511, Japan

2Department of Hematology, Graduate School of Medicine, Osaka City University, Abeno, Osaka 545-8585, Japan

3Department of Genome Biology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka 589-8511, Japan

4Department of Pathology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka 589-8511, Japan

Correspondence to:

Hidetoshi Hayashi, email: [email protected]

Keywords: non–small cell lung cancer (NSCLC); L1196M; anaplastic lymphoma kinase (ALK) fusion gene; ceritinib; alectinib

Received: December 26, 2017     Accepted: April 02, 2018     Published: May 01, 2018

ABSTRACT

The second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) alectinib and ceritinib are standard treatment options for patients with non–small cell lung cancer (NSCLC) positive for ALK fusion genes. However, almost all patients eventually develop resistance to these drugs. We here report a case of ALK-rearranged NSCLC that developed resistance to alectinib but remained sensitive to ceritinib. The L1196M mutation within the ALK fusion gene was detected after failure of consecutive treatment with crizotinib and alectinib, but no other mechanism underlying acquired resistance to ALK-TKIs was found to be operative. Given the increasing application of ALK-TKIs to the treatment of patients with ALK-rearranged NSCLC, further clinical evaluation is warranted to provide a better understanding of the mechanisms of acquired resistance to these agents and to inform treatment strategies for such tumors harboring secondary mutations.


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