Bosutinib in Japanese patients with newly diagnosed chronic-phase chronic myeloid leukemia: final 3-year follow-up results of a phase 2 study

Abstract

Bosutinib has been evaluated for treatment of chronic-phase chronic myeloid leukemia (CP-CML) in several clinical studies, including in Japan. This open-label, single-arm, phase 2 study evaluated the efficacy and safety of bosutinib at a starting dose of 400 mg once daily in Japanese patients (n = 60) with newly diagnosed CP-CML. The minimum follow-up period was 3 years and median duration of treatment was 35.9 months. At study completion, 60% of patients were still on treatment. Cumulative rates of major molecular response (MMR), molecular response4 (MR4), and MR4.5 at any time were 70.0%, 53.3%, and 48.3%, respectively. No patient who achieved MMR or MR4 had a confirmed loss of response. No patient experienced on-treatment transformation to accelerated/blast phase or died within 28 days of the last bosutinib dose. Any-grade treatment-emergent adverse events (TEAEs) occurred in 100% (grade ≥ 3: 81.7%) of patients. The most common TEAEs were diarrhea (86.7%), increased alanine aminotransferase (55.0%), and increased aspartate aminotransferase (46.7%). No new safety signals emerged during the follow-up period. Bosutinib continues to demonstrate a favorable benefit/risk profile and is an important treatment option for Japanese patients with newly diagnosed CP-CML. Optimal management of TEAEs during initial treatment with bosutinib should be prioritized.Trial Registration: ClinicalTrials.gov ID: NCT03128411.

Keywords: Bosutinib; Chronic myeloid leukemia; Japan; Tyrosine kinase inhibitor.

Conflict of interest statement

Takaaki Ono reports honoraria from Bristol Myers Squibb, Celgene, Merck Sharp & Dohme, Ono, Otsuka, Novartis, Pfizer, and Takeda; and research funding from Celgene, Chugai, Kyowa Hakko Kirin, Merck Sharp & Dohme, and Ono. Masayuki Hino reports research funding from Novartis, Otsuka, and Pfizer; and honoraria from Bristol Myers Squibb, Novartis, Otsuka, and Pfizer. Itaru Matsumura reports research funding from Otsuka and Pfizer; speakers bureau with Bristol Myers Squibb and Novartis; and consultancy with Otsuka. Shin Fujisawa reports honoraria and research funding from Bristol Myers Squibb, Novartis, Otsuka, and Pfizer. Kenichi Ishizawa reports research funding from Otsuka and Pfizer; and speakers bureau with Bristol Myers Squibb and Novartis. Emiko Sakaida reports research funding from Bristol Myers Squibb, Chugai, Kyowa Kirin, and Ono; and honoraria from Bristol Myers Squibb, Novartis, and Pfizer. Naohiro Sekiguchi reports research funding from A2 Healthcare, Astellas, Bristol Myers Squibb, Daiichi Sankyo, Janssen, Merck Sharp & Dohme, Ono, Otsuka, Pfizer, PPD-SNBL, and Sumitomo Dainippon Pharma. Chiho Ono reports employment by Pfizer Japan Inc and stock options for Pfizer. Mana Aizawa, Yusuke Tanetsugu, and Yuichiro Koide report employment for Pfizer R&D Japan G.K. Naoto Takahashi reports research funding and honoraria from Novartis, Otsuka, and Pfizer; and research funding from Asahi Kasei, Chugai, Eisai, Kyowa Hakko Kirin, Ono, and Toyama Kagaku.

© 2022. The Author(s).

Figures

Fig. 1

Bosutinib daily dose over time. As-treated population. Patients on treatment at each timepoint were included. The first non-zero actual dose in each interval was used; if all doses in each interval were 0 mg, they were counted as 0 mg. QD once daily

Fig. 2

Cumulative incidence (≥ 15%)a of newly occurring TEAEs of any grade, by treatment year. As-treated population. One year = 365.25 days. aDefinitions of TEAEs of special interest categories (cardiac, vascular, hypertension, renal, rash) are provided in Supplementary Table S1. ALP alkaline phosphatase; ALT alanine aminotransferase, AST aspartate aminotransferase, GGT gamma-glutamyltransferase, TEAE treatment-emergent adverse event