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.

Population modeling of bosutinib exposure‐response in patients with newly diagnosed chronic phase chronic myeloid leukemia

“…The reason for a higher rate of discontinuation in B1871048 was unclear. The final 3‐year follow‐up of B1871048 demonstrated that most permanent discontinuations due to AEs occurred within the first 6 months of bosutinib treatment 11 . A significant exposure–response relationship was identified between time‐to‐event and log( C avg ), C trough , and C avg with diarrhea, nausea, and vomiting, respectively (Table S6).…”

“…The final 3‐year follow‐up of B1871048 demonstrated that most permanent discontinuations due to AEs occurred within the first 6 months of bosutinib treatment. 11 A significant exposure–response relationship was identified between time‐to‐event and log( C avg ), C trough , and C avg with diarrhea, nausea, and vomiting, respectively (Table S6 ). No demographic covariates were found to be statistically significant on any of these safety endpoints.…”

An Overview of Advances in Rare Cancer Diagnosis and Treatment

“…As a result, it has shown beneficial effects after treatment with 45 mg of ponatinib as a starting dose, which leads to 44.1% of primary endpoint achievement in 12 months [115]. Other types of TKIs are also used in rare cancer treatments, including pazopanib and cabozantinib for Merkel cell carcinoma, sorafenib, which targets vascular endothelial growth factor receptor (VEGFR), PDGFR, and RAF kinases for thymic carcinoma, EGFR and VEGFR for esophageal cancer, ABL001 (Asciminib) [91], as well as bosutinib in CML [116].…”