Phase II study of ceritinib in alectinib-pretreated patients with anaplastic lymphoma kinase-rearranged metastatic non-small-cell lung cancer in Japan: ASCEND-9

Toyoaki Hida, Takashi Seto, Hidehito Horinouchi, Makoto Maemondo, Masayuki Takeda, Katsuyuki Hotta, Fumihiko Hirai, Young Hak Kim, Shingo Matsumoto, Masayuki Ito, Koichi Ayukawa, Kota Tokushige, Masataka Yonemura, Testuya Mitsudomi, Makoto Nishio

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Abstract

Clinical experience of ceritinib in patients who progressed on alectinib is limited. In this prospective phase II study, we evaluated the activity of ceritinib in alectinib-pretreated patients with anaplastic lymphoma kinase (ALK)-rearranged metastatic (stage IIIB/IV) non-small-cell lung cancer (NSCLC) in Japan. All patients were required to have ≥1 measurable lesion per RECIST, 1.1, and a World Health Organization Performance Status (WHO PS) of 0-1. Prior crizotinib and/or up to 1 chemotherapy regimen was allowed. Primary endpoint was investigator-assessed overall response rate (ORR) per RECIST 1.1. Ceritinib was given at a dose of 750 mg/day fasted. A total of 20 patients were enrolled from August 2015 to March 2017. All patients received prior alectinib (100%), 13 (65.0%) patients received prior platinum-based chemotherapy, and 4 (20%) patients received prior crizotinib. Median duration of exposure and the follow-up time with ceritinib were 3.7 months (range: 0.4-15.1) and 11.6 months (range: 4.8-23.0), respectively. Investigator-assessed ORR was 25% (95% CI: 8.7-49.1). Key secondary endpoints, all investigator assessed, included disease control rate (70.0%; 95% CI: 45.7-88.1), time to response (median, 1.8 months; range: 1.8-2.0), and duration of response (median, 6.3 months; 95% CI: 3.5-9.2). Median progression-free survival was 3.7 months (95% CI: 1.9-5.3). The most common adverse events reported were diarrhea (85.0%), nausea (80.0%), and vomiting (65.0%). Based on our findings, ceritinib could be considered as one of the treatment options for patients with ALK-positive NSCLC who progressed on alectinib. (Trial registration no. NCT02450903).

Original languageEnglish
Pages (from-to)2863-2872
Number of pages10
JournalCancer Science
Volume109
Issue number9
DOIs
Publication statusPublished - Sep 2018

Keywords

  • ALK
  • Japan
  • NSCLC
  • anaplastic lymphoma kinase
  • ceritinib

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Hida, T., Seto, T., Horinouchi, H., Maemondo, M., Takeda, M., Hotta, K., Hirai, F., Kim, Y. H., Matsumoto, S., Ito, M., Ayukawa, K., Tokushige, K., Yonemura, M., Mitsudomi, T., & Nishio, M. (2018). Phase II study of ceritinib in alectinib-pretreated patients with anaplastic lymphoma kinase-rearranged metastatic non-small-cell lung cancer in Japan: ASCEND-9. Cancer Science, 109(9), 2863-2872. https://doi.org/10.1111/cas.13721