ASH Clinical News June 2016 | Page 25

CLINICAL NEWS prior treatment (except for corticosteroids or single-dose vincristine). After pre-treatment with dexamethasone (10 mg/day on days 3-7) and one intrathecal dose of methotrexate (15 mg), the study protocol consisted of: 5.5” .25” • Induction: dasatinib 140 mg, once daily during induction, plus weekly vincristine 2 mg administered intravenously (IV) and dexamethasone 40 mg for 2 days (20 mg for patients >70 years) for 4 weeks • Consolidation: dasatinib 100 mg/day sequentially with methotrexate 1,000 mg/m2 on day 1 and asparaginase 10,000 UI/m2 on day 2 of cycles 1, 3, and 5; and cytarabine 1,000 mg/m2 every 12 hours on days 1, 3, and 5 of G:.5” cycles 2, 4, and 6 • Maintenance: dasatinib 100 mg/day sequentially with 6-mercaptopurine 60 mg/m2/day and methotrexate 25 mg/m2/week administered orally once every other month and dexamethasone/vincristine every 2-3 months for up to 24 months Dasatinib at a dose of 100 mg was administered daily after maintenance therapy until relapse or death. Patients were permitted to undergo alloHCT or autologous HCT (AHCT) with reduced-intensity conditioning or myeloablative conditioning. At the beginning of the study, the researchers noticed an excess rate of treatment discontinuation in the first 11 patients S:6.75” BOSULIF offers proven efficacy for patients with resistance or intolerance to prior therapy2 In 2nd-line treatment, after imatinib (n=266 evaluable)a 34 % of patients 53 % of patients achieved MCyR at 6 months achieved MCyR with a minimum follow-up of 23 months (95% CI: 28.2, 39.9) Median duration of MCyR was not reached at the time of analysis 53% of patients with MCyR maintained MCyR for at least 18 months (with a minimum follow-up of 23 months) In 3rd-line treatment, after imatinib followed by nilotinib and/or dasatinib therapy (n=108 evaluable) • 27% of patients achieved MCyR by 6 months (95% CI: 18.8, 36.2) • 32% of patients achieved MCyR with a minimum follow-up of 13 months • Median duration of MCyR was not reached at the time of analysis — 51% of patients with MCyR maintained MCyR for at least 9 months (with a minimum follow-up of 13 months) BOSULIF has a distinct safety and tolerability profile2 Warnings and precautions include: gastrointestinal toxicity, myelosuppression, hepatic toxicity, fluid retention, renal toxicity, and embryofetal toxicity. Please see Important Safety Information below for more detail. Most common adverse reactions observed in ≥20% of patients in the Phase 1/2 safety population (N=546) Most common Grade 3/4 adverse reactions observed in ≥10% of patients All grades (%) Grade 3/4 (%) Nausea (46) Anemia (27) Anemia (13) Thrombocytopenia (41) Pyrexia (26) Neutropenia (12) Vomiting (39) Fatigue (24) Abdominal pain (37) a Median duration of treatment was 22 months for evaluable patients. MCyR=major cytogenetic response. For more information on BOSULIF, visit www.BosulifHCP.com. Embryofetal Toxicity: BOSULIF may cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised of potential hazard to the fetus and to avoid becoming pregnant while receiving BOSULIF. Adverse Reactions: The most common adverse reactions observed in greater than 20% of patients in the Phase 1/2 safety population (N=546) were diarrhea, nausea, thrombocytopenia, vomiting, abdominal pain, rash, anemia, pyrexia, and fatigue. The most common Grade 3/4 adverse reactions and laboratory abnormalities observed in greater than 10% of patients were thrombocytopenia, anemia, and neutropenia. CYP3A Inhibitors and Inducers: Avoid concurrent use with strong or moderate CYP3A inhibitors or inducers. Proton Pump Inhibitors: Consider using short-acting antacids or H2 blockers instead of PPIs to avoid a reduction in BOSULIF exposure. Separate antacid or H2 blocker dosing and BOSULIF dosing by more than 2 hours. Nursing Mothers: Given the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or BOSULIF, taking into account the importance of the drug to the mother. References: 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Myelogenous Leukemia V.1.2016. © National Comprehensive Cancer Network, Inc. 2015. All rights reserved. Accessed October 27, 2015. To view the most recent and complete version of the guideline, go online to NCCN.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc. 2. BOSULIF Prescribing Information. New York, NY: Pfizer Inc. Please see brief summary of full Prescribing Information on the following pages. PP-BOS-USA-0154-01 © 2016 Pfizer Inc. All rights reserved. March 2016 T:10.5” Thrombocytopenia (29) B:10.75” Rash (35) S:9.75” Diarrhea (82)