| Autor: |
Hida, Toyoaki, Nakagawa, Kazuhiko, Seto, Takashi, Satouchi, Miyako, Nishio, Makoto, Hotta, Katsuyuki, Takahashi, Toshiaki, Ohe, Yuichiro, Takeda, Koji, Tatsuno, Masahiro, Asakawa, Takashi, Shimada, Tadashi, Tanaka, Tomohiro, Tamura, Tomohide |
| Zdroj: |
Cancer Science; Nov2016, Vol. 107 Issue 11, p1642-1646, 5p |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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