Dasatinib 100 mg Once Daily Minimizes the Occurrence of Pleural Effusion in Patients With Chronic Myeloid Leukemia in Chronic Phase and Efficacy Is Unaffected in Patients who Develop Pleural Effusion

• Type of Material: Article
• Authors: Kimmo Porkka, University of Helsinki; Hanna Khoury, Emory University; Ronald L. Paquette, Ronald Reagan UCLA Medical Center; Yousif Matloub, Bristol Myers Squibb; Ritwik Sinha, Bristol Myers Squibb; Jorge E. Cortes, University of Texas
• Language: English
• Date: 2010-01-15
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2010 American Cancer Society.
• Final Published Version (URL): http://dx.doi.org/10.1002/cncr.24734
• Title of Journal or Parent Work: Cancer
• ISSN: 0008-543X
• Volume: 116
• Issue: 2
• Start Page: 377
• End Page: 386
• Grant/Funding Information: Funding for the clinical trial, statistical analysis, and medical writing assistance was provided by Bristol-Myers Squibb (BMS).; Ronald L. Paquette has acted as a consultant for BMS, Alexion, and Telik, and has received honoraria and is a member of the Speakers Bureau for BMS and Novartis.; Jorge E. Cortes has received research funding from BMS, Wyeth, and Novartis.; Kimmo Porkka has acted as a consultant, received honoraria, and received research funding from BMS and Novartis.; H. Jean Khoury has received honoraria from BMS, Novartis, and Genzyme.
• Keywords: Oncology; Science & Technology; FAILURE; THERAPY; INTOLERANCE; IMATINIB-RESISTANT; CHRONIC MYELOGENOUS LEUKEMIA; treatment outcome; chronic myeloid leukemia; CELLS; progression-free survival; pleural effusion; Life Sciences & Biomedicine; INHIBITION; Dasatinib; lymphocytosis; CYTOGENETIC RESPONSES
• Research Categories: Health Sciences, Oncology; Health Sciences, Medicine and Surgery

Abstract

BACKGROUND: Dasatinib, a highly potent BCR-ABL inhibitor, is an effective treatment for patients with chronic myeloid leukemia in chronic phase (CML CP) after resistance, suboptimal response, or intolerance to prior imatinib. In a phase 3 dose optimization trial in patients with CML CP (CA180-034), the occurrence of pleural effusion was significantly minimized with dasatinib 100 mg once daily (QD) compared with other treatment arms (70 mg twice daily [twice daily], 140 mg QD, or 50 mg twice daily). METHODS: To investigate the occurrence and management of pleural effusion during dasatinib treatment, and efficacy in patients with or without pleural effusion, data from CA180-034 were analyzed. RESULTS: With 24-month minimum follow-up, 14% of patients treated with dasatinib 100 mg QD incurred pleural effusion (grade 3: 2%; grade 4: 0%) compared with 23% to 26% in other study arms. The pleural effusion rate showed only a minimal increment from 12 to 24 months. In the 100 mg QD study arm, median time to pleural effusion (any grade) was 315 days, and after pleural effusion, 52% of patients had a transient dose interruption, 35% had a dose reduction, 57% received a diuretic, and 26% received a corticosteroid. Three patients in the 100 mg QD study arm discontinued treatment after pleural effusion. Across all study arms, patients with or without pleural effusion demonstrated similar progression-free and overall survival, and cytogenetic response rates were higher in patients with a pleural effusion. CONCLUSIONS: Pleural effusion is minimized with dasatinib 100 mg QD dosing and its occurrence does not affect short- or long-term efficacy.