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. 2010 Jan 15;116(2):377-86.
doi: 10.1002/cncr.24734.

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

Kimmo Porkka  1 , H Jean Khoury, Ronald L Paquette, Yousif Matloub, Ritwik Sinha, Jorge E Cortes
Affiliations

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

Kimmo Porkka et al. Cancer. .

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.

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Conflict of interest statement

CONFLICT OF INTEREST DISCLOSURES

Funding for the clinical trial, statistical analysis, and medical writing assistance was provided by Bristol-Myers Squibb (BMS). 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. 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. Yousif Matloub and Ritwik Sinha own equity in and are employees of BMS. Yousif Matloub owns equity in GlaxoSmithKline. Jorge E. Cortes has received research funding from BMS, Wyeth, and Novartis.

Figures

Figure 1
Figure 1
Depicted is the Kaplan-Meier analysis of duration of dasatinib treatment until pleural effusion (any grade). Patients were censored at the end of dasatinib treatment. BID indicates twice daily; QD, once daily.
Figure 2
Figure 2
Analysis of baseline patient characteristics and lymphocytosis during treatment as risk factors for pleural effusion is shown.
Figure 3
Figure 3
Kaplan-Meier analysis of duration of major cytogenetic response (major cytogenetic response) in patients with or without pleural effusion is illustrated. (A) Dasatinib 100 mg once-daily arm. (B) All treated patients.
Figure 4
Figure 4
Kaplan-Meier analysis of progression-free survival in patients with or without pleural effusion is depicted. (A) Dasatinib 100 mg once-daily arm. (B) All treated patients.
Figure 5
Figure 5
Kaplan-Meier analysis of overall survival in patients with or without pleural effusion is shown. (A) Dasatinib 100 mg once-daily arm. (B) All treated patients.
See this image and copyright information in PMC

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