Pharmacologic study (JP28927) of alectinib in Japanese patients with ALK+ non-small-cell lung cancer with or without prior crizotinib therapy

Toyoaki Hida, Kazuhiko Nakagawa, Takashi Seto, Miyako Satouchi, Makoto Nishio, Katsuyuki Hotta, Toshiaki Takahashi, Yuichiro Ohe, Koji Takeda, Masahiro Tatsuno, Takashi Asakawa, Tadashi Shimada, Tomohiro Tanaka, Tomohide Tamura

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12 Citations (Scopus)

Abstract

We report pharmacokinetics, efficacy and safety data for a new 150-mg alectinib capsule in ALK+ non-small-cell lung cancer in a multicenter, open-label pharmacologic study (JP28927). Eligible patients (≥20 years, locally advanced/metastatic ALK+ disease, ALK inhibitor-naïve and -pretreated [including crizotinib refractory]) were randomized 1:1 to receive one of two sequences of alectinib 300 mg twice daily (comprising different schedules of 20/40-mg and 150-mg capsules) until investigator-determined lack of clinical benefit. Co-primary endpoints were: bioequivalence of alectinib 20/40 mg vs 150 mg; food effect with 150 mg; and safety. Thirty-five patients were enrolled; median treatment duration was 13.1 months (range 1.1−15.0). Under fasting conditions, exposure of the two formulations was similar; mean AUClast ± standard deviation 3230 ± 914 h·ng/mL vs 3710 ± 1040 h·ng/mL, respectively, for 150-mg vs 20/40-mg capsules. Food effect with 150 mg alectinib was negligible. Treatment-related adverse events in >20% of patients were constipation (31.4%), dysgeusia (25.7%), and decreased white blood cell and neutrophil count (22.9% each). No treatment-related grade 4/5 events occurred. Median time to response was 1.2 months (95% CI 1.1−2.1). For the full analysis set (n = 35) and crizotinib-failure subpopulations (n = 23), the overall response rate was 70.0% (95% CI 50.6−85.3) and 65.0% (95% CI 40.8−84.6), and median progression-free survival was 13.9 months (95% CI 11.1−not reached) and 12.9 months (95% CI 3.9−not reached), respectively. The 150-mg capsule had a similar exposure profile to 20/40-mg capsules. Alectinib demonstrated promising efficacy and was well tolerated.

Original languageEnglish
Pages (from-to)1642-1646
Number of pages5
JournalCancer Science
Volume107
Issue number11
DOIs
Publication statusPublished - Nov 1 2016

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Keywords

  • Alectinib
  • anaplastic lymphoma kinase
  • bioequivalence
  • Japanese
  • non-small-cell lung cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Hida, T., Nakagawa, K., Seto, T., Satouchi, M., Nishio, M., Hotta, K., Takahashi, T., Ohe, Y., Takeda, K., Tatsuno, M., Asakawa, T., Shimada, T., Tanaka, T., & Tamura, T. (2016). Pharmacologic study (JP28927) of alectinib in Japanese patients with ALK+ non-small-cell lung cancer with or without prior crizotinib therapy. Cancer Science, 107(11), 1642-1646. https://doi.org/10.1111/cas.13066