Dasatinib (D) in patients with accelerated phase chronic myeloid leukemia (AP-CML) who are resistant or intolerant to imatinib: Results of the CA180005 ’START-A’ study

• Published in: Journal of clinical oncology Vol. 24; no. 18_suppl; p. 6526
• Main Authors: Talpaz, M., Apperley, J. F., Kim, D. W., Silver, R. T., Bullorsky, E. O., Cheng, S., Iyer, M., Guilhot, F.
• Format: Journal Article
• Language: English
• Published: 20.06.2006
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/jco.2006.24.18_suppl.6526

Abstract only 6526 Background: Dasatinib (D) (BMS-354825) is an oral multi-targeted kinase inhibitor with preliminary evidence of efficacy in a previously reported phase I study. START A is an open-label study of dasatinib in AP-CML pts who were imatinib resistant (IM-R) or imatinib intolerant (IM-I). Methods: A total of 192 pts were enrolled between December 2004 and Jun 2005 in 39 centers worldwide. Dasatinib was given orally at 70 mg twice daily (BID). Dose escalations to 100 mg BID were allowed for poor initial response and reductions to 50 or 40 mg BID for persistent toxicity. Evaluations were weekly blood counts and monthly bone marrow evaluation including cytogenetics. The primary endpoint was major confirmed (maintained at least 4 weeks) hematologic response (MaHR) in IM-R pts. Results: The first 107 pts (99 IM-R, 8 IM-I) with at least 6 months of follow-up are currently reported; there were 55 males/52 females; median age 57 years (range 23–86); median time from diagnosis of CML 90.9 months. Prior therapy included IM>600 mg/day in 63 (59%) pts, interferon in 80 (75%) pts. Major cytogenetic response (MCyR) to prior IM was seen in 34 (32%) pts. 56 pts had Bcr-Abl kinase domain mutations. Median duration of therapy was 5.5 months. MaHR was documented in 63 (59%) pts (95% CI: 49–68) with complete hematologic response in 35 (33%) and no evidence of leukemia in 28 (26%). In IM-R pts, the MaHR rate was 59%. MCyR was documented in 33 (32%) pts (95% CI: 22.9–41.6); complete in 23 (22%), partial in 10 (10%). MaHR were seen in pts with Bcr-Abl mutations and in pts who never responded to IM. Molecular response analysis is ongoing. There were 15 disease progressions including one loss of MaHR. Myelosuppression was significant with grade 3–4 thrombocytopenia and neutropenia in 79% and 69% of pts, respectively. Non-hematologic toxicities were generally mild to moderate. The most frequent were diarrhea (46%), peripheral edema (27%), pleural effusion (16%), rash (8%), and GI hemorrhage (7%). Conclusions: Dasatinib was very effective in IM-R pts with AP-CML with high rates of durable MaHR and MCyR. Data on all 192 pts will be presented at the meeting. [Table: see text]