Dasatinib 2-year efficacy in patients with chronic-phase chronic myelogenous leukemia (CML-CP) with resistance or intolerance to imatinib (START-C)

Abstract

7009 Background: Dasatinib is 325-fold more potent than imatinib and 16-fold more potent than nilotinib against BCR-ABL in vitro. Extended 2-year follow-up data are available for the START-C study, an international, 75-center, phase II study in patients (pts) with CML-CP resistant or intolerant to imatinib. Methods: Pts were required to be either imatinib-resistant or -intolerant. The starting dose was dasatinib 70 mg BID, with dose escalations (90 mg BID) or reductions (50 or 40 mg BID) allowed for lack of response or toxicity. The primary endpoint was major cytogenetic response rate (MCyR). Results: Median time from CML diagnosis at baseline was 61 mos (range 3- 251). Best response to prior imatinib therapy was complete hematologic response (CHR) in 82%, complete cytogenetic response (CCyR) in 19%, and MCyR in 37% of pts. After a minimum follow up of 24 mos (LPFV to database closure; n=387, 288 imatinib-resistant, 99 imatinib-intolerant), CHR was noted in 91% (95% CI 88–94%), MCyR in 62% (95% CI 57–67%), CCyR in 53% and major molecular response (MMR) in 47% of pts. Rates of MCyR were 55% for imatinib-resistant pts, and 63% for pts with baseline BCR-ABL mutations; responses were seen across all mutations except T315I. In imatinib-intolerant pts, the CCyR (n=99) rate and MMR (n=94 evaluable) rate were both 78%. MCyRs were durable, with 88% of pts maintaining response at 24 mos. Progression-free survival (PFS) at 24 mos was 80% (75% in imatinib-resistant and 94% in imatinib-intolerant pts). Overall survival at 24 mos was 94% (92% in imatinib -resistant and 100% in imatinib-intolerant pts). Grade 3–4 toxicities included thrombocytopenia (49%) and neutropenia (50%), pleural effusion (9%), dyspnea (6%), bleeding (4%), diarrhea (3%), and fatigue (3%). 3% of imatinib-intolerant pts developed similar grade 3–4 toxicities; all were able to continue treatment after dose reduction, demonstrating lack of cross intolerance. The appearance of new higher grade toxicity between 12 and 24 months was uncommon. Conclusions: Dasatinib is well-tolerated in pts with CML-CP and induces cytogenetic responses that are highly durable and result in a PFS of 80% at 24-mos. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb, Novartis Bristol-Myers Squibb Bristol-Myers Squibb, Novartis Bristol-Myers Squibb, Novartis Bristol-Myers Squibb