Abstract 4715: Dasatinib as initial therapy for patients with chronic myeloid leukemia (CML) in early chronic phase (CP)

Dasatinib is approximately 300 times more potent than imatinib in vitro and has significant activity in patients (pts) with CML-CP resistant or intolerant of imatinib (IM). We initiated a phase II trial to study the efficacy and safety of dasatinib in pts with previously untreated CML-CP. Aims: To investigate the efficacy and safety of dasatinib as initial therapy for patients with CML-CP. Methods: The primary objective was to estimate the proportion of pts attaining major molecular response at 12 months (mo). Pts with previously untreated CML-CP within 6 mo from diagnosis were eligible and received dasatinib 100 mg/day, randomized to either 50 mg twice daily (BID) or 100 mg once daily (QD). After 66 pts were accrued, the BID arm was closed and all subsequent pts were treated with 100 mg QD. Results: 82 pts have been enrolled (49 on the QD schedule, 33 BID). Median age was 47 years (yrs) (range 18-76 yrs). Median follow-up is 29 mo (range, 0 to 54 mo). All 72 pts who were not in CHR at the start of therapy achieved CHR. Among 75 pts followed for at least 3 mo, 73 (97%) achieved complete cytogenetic response (CCyR). Major molecular response (MMR) has been achieved in 64 (86%), including 19 (26%) with complete molecular response. The CCyR rate at different timepoints compares favorably to that observed in historical controls treated with imatinib 400mg or 800 mg daily. MMR was observed in 81% and 82% of the QD and BID patients respectively. However, the 12 mo MMR trended slightly higher with the BID dosing schedule compared to the QD schedule: 81% and 71% (p=0.384) respectively. Grade 3-4 non-hematologic toxicity included pain (muscle or joint) (13%), fatigue (11%), dyspnea (7%), neuropathy (6%), memory impairment, headache (5% each), diarrhea, pleural effusion, musculoskeletal complaints (2% each) and rash, prolonged QTC, weight gain and pruritus (1% each). Pleural effusion occurred in 16% evaluable pts. Grade 3-4 hematologic toxicity (transient) included thrombocytopenia 13%, neutropenia 25%, and anemia 9%. Fifty-two (63%) of 82 pts required transient treatment interruptions. The actual median daily dose for all pts was 100mg. There is no significant difference in grade 3-4 toxicity by treatment schedule but there was a trend for less pleural effusion with QD (13%) vs BID (22%; p=0.267). Five pts lost CCyR:(including 2 because of non-compliance). The 24-month probability of event-free survival (EFS) is 88%. There have been no transformations on study, and only one patient has died (metastatic pancreatic cancer). Ten patients have discontinued therapy (3 patient choice, 5 toxicity 2 pleural effusion, 1 prolonged thrombocytopenia, 1 bone pain, 1 congestive heart failure, and 2 for loss of MCyR) Conclusion: Rapid CCyR occurs in nearly all patients with previously untreated CML-CP treated with frontline dasatinib therapy; the MMR rate at 24 months was 93%, with a favorable toxicity profile. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4715. doi:10.1158/1538-7445.AM2011-4715