Long‐term efficacy and safety of bosutinib in patients with advanced leukemia following resistance/intolerance to imatinib and other tyrosine kinase inhibitors

• Type of Material: Article
• Authors: Carlo Gambacorti-Passerini, University of Milano-Bicocca; Hagop M. Kantarjian, University of Texas MD Anderson Cancer Center; Dong-Wook Kim, Seoul St. Mary's Hospital; Hanna Khoury, Emory University; Anna G. Turkina, Hematology Research Center Russia; Tim H. Brummendorf, Universitätsklinikum Aachen; Ewa Matczak, Pfizer; Nathalie Bardy-Bouxin, Pfizer Global Research and Development; Mark Shapiro, Pfizer; Kathleen Tumbull, Pfizer; Eric Leip, Pfizer; Jorge E. Cortes, University of Texas MD Anderson Cancer Center
• Language: English
• Date: 2015-06-01
• Publisher: Wiley
• Publication Version: Final Published Version
• Copyright Statement: © 2015 The Authors. American Journal of Hematology Published by Wiley Periodicals, Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1002/ajh.24034
• Title of Journal or Parent Work: AMERICAN JOURNAL OF HEMATOLOGY
• Volume: 90
• Issue: 9
• Start Page: 755
• End Page: 768
• Grant/Funding Information: This study was sponsored by Wyeth Research, which was acquired by Pfizer in October 2009. Programming support was provided by ICON plc.
• Keywords: hematologic resonse; long-term efficacy; blast-phase; chronic myeloid leukemia; treatment failure; treatment duration; leukemia; acute lymphoblastic leukemia; bosutinib
• Research Categories: Biology, Cell

Abstract

Long‐term efficacy and safety of bosutinib (≥4 years follow‐up from last enrolled patient) were evaluated in an ongoing phase 1/2 study in the advanced leukemia cohort with prior treatment failure (accelerated‐phase [AP, n = 79] chronic myeloid leukemia [CML], blast‐phase [BP, n = 64] CML, acute lymphoblastic leukemia [ALL, n = 24]). Fourteen AP, 2 BP, and 1 ALL patient remained on bosutinib at 4 years (vs. 38, 8, 1 at 1 year); median (range) treatment durations: 10.2 (0.1–88.6), 2.8 (0.03–55.9), 0.97 (0.3–89.2) months. Among AP and BP patients, 57% and 28% newly attained or maintained baseline overall hematologic response (OHR); 40% and 37% attained/maintained major cytogenetic response (MCyR) by 4 years (most by 12 months). In responders at 1 versus 4 years, Kaplan‐Meier (KM) probabilities of maintaining OHR were 78% versus 49% (AP) and 28% versus 19% (BP); KM probabilities of maintaining MCyR were 65% versus 49% (AP) and 21% versus 21% (BP). Most common AEs (AP, BP) were gastrointestinal (96%; 83%), primarily diarrhea (85%; 64%), which was typically low grade (maximum grade 1/2: 81%; 59%) and transient; no patient discontinued due to diarrhea. Serious AEs occurred in 44 (56%) AP and 37 (58%) BP patients, most commonly pneumonia (n = 9) for AP and pyrexia (n = 6) for BP; 11 and 13 died within 30 days of last dose (2 considered bosutinib‐related [AP] per investigator). Responses were durable in ∼50% AP responders at 4 years (∼25% BP patients responded at year 1, suggesting possible bridge‐to‐transplant role in BP patients); toxicity was manageable.