Factors influencing long‐term efficacy and tolerability of bosutinib in chronic phase chronic myeloid leukaemia resistant or intolerant to imatinib

• Published in: British journal of haematology Vol. 172; no. 1; pp. 97 - 110
• Main Authors: Brümmendorf, Tim H., Cortes, Jorge E., Khoury, Hanna J., Kantarjian, Hagop M., Kim, Dong‐Wook, Schafhausen, Philippe, Conlan, Maureen G., Shapiro, Mark, Turnbull, Kathleen, Leip, Eric, Gambacorti‐Passerini, Carlo, Lipton, Jeff H.
• Format: Journal Article
• Language: English
• Published: England John Wiley and Sons Inc 01.01.2016
• Subjects: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Aniline Compounds - adverse effects; Aniline Compounds - therapeutic use; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; bosutinib; chronic myeloid leukaemia; Drug Resistance, Neoplasm; Female; Follow-Up Studies; Fusion Proteins, bcr-abl - genetics; Haematological Malignancy; Humans; Imatinib Mesylate - therapeutic use; Kaplan-Meier Estimate; Leukemia, Myeloid, Chronic-Phase - drug therapy; Leukemia, Myeloid, Chronic-Phase - genetics; Male; Middle Aged; Mutation; Nitriles - adverse effects; Nitriles - therapeutic use; Quinolines - adverse effects; Quinolines - therapeutic use; Research Paper; second‐line therapy; Treatment Outcome; tyrosine kinase inhibitor; Young Adult; second-line therapy; tyrosine kinase inhibitor; bosutinib; chronic myeloid leukaemia
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/bjh.13801

Summary The dual SRC/ABL1 tyrosine kinase inhibitor bosutinib is indicated for adults with Ph+ chronic myeloid leukaemia (CML) resistant/intolerant to prior therapy. This analysis of an ongoing phase 1/2 study (NCT00261846) assessed effects of baseline patient characteristics on long‐term efficacy and safety of bosutinib 500 mg/day in adults with imatinib (IM)‐resistant (IM‐R; n = 196)/IM‐intolerant (IM‐I; n = 90) chronic phase (CP) CML. Median treatment duration was 24·8 months (median follow‐up, 43·6 months). Cumulative major cytogenetic response (MCyR) rate [95% confidence interval (CI)], was 59% (53–65%); Kaplan‐Meier (KM) probability of maintaining MCyR at 4 years was 75% (66–81%). Cumulative incidence of on‐treatment progression/death at 4 years was 19% (95% CI, 15–24%); KM 2‐year overall survival was 91% (87–94%). Significant baseline predictors of both MCyR and complete cytogenetic response (newly attained/maintained from baseline) at 3 and 6 months included prior IM cytogenetic response, baseline MCyR, prior interferon therapy and <6 months duration from diagnosis to IM treatment initiation and no interferon treatment before IM. The most common adverse event (AE) was diarrhoea (86%). Baseline bosutinib‐sensitive BCR‐ABL1 mutation was the only significant predictor of grade 3/4 diarrhoea; no significant predictors were identified for liver‐related AEs. Bosutinib demonstrates durable efficacy and manageable toxicity in IM‐R/IM‐I CP‐CML patients.