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Dasatinib (Sprycel) Gets Label Update

Prescribing information includes new long-term efficacy and safety data

The FDA has approved an update to the product labeling for dasatinib (Sprycel, Bristol-Myers Squibb/Otsuka America Pharmaceutical). The labeling now includes 5-year efficacy and safety data in adult patients with newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP) and 7-year data in CP Ph+ CML patients who were resistant to or intolerant of prior therapy, including imatinib mesylate (Gleevec, Novartis).

The DASISION trial was an open-label, randomized, phase III international study of dasatinib 100 mg once-daily (n = 259) compared with imatinib 400 mg once-daily (n = 260) in the treatment of patients with newly diagnosed CP Ph+ CML. The study’s primary endpoint was a confirmed complete cytogenetic response (CCyR) by 1 year, and secondary endpoints included a major molecular response (MMR) at any time, the time to MMR, and the time to confirmed CCyR. With a minimum of 5 years of follow-up, 61% of the dasatinib group and 62% of the imatinib group were still on treatment at the time of the final analysis.

In the DASISION trial, 77% of patients treated with dasatinib and 66% of patients treated with imatinib achieved confirmed CCyR (defined as two consecutive assessments of CCyR at least 4 weeks apart) by 1 year (P = 0.007). After 5 years of follow-up, the median times to confirmed CCyR were 3.1 months in 215 dasatinib responders and 5.8 months in 204 imatinib responders. In the long-term (by 5 years), confirmed CCyR rates were 83% for dasatinib and 79% for imatinib.

Dasatinib-treated patients were more likely than imatinib-treated patients to achieve MMR by 1 year (52% vs. 34%, respectively; P < 0.0001). In the long-term (by 5 years), the MMR rate at any time was higher for dasatinib than for imatinib (76% vs. 64%, respectively).

The dose-optimization study (CA180-034) was an open-label, randomized trial designed to assess the efficacy and safety of dasatinib in patients with CP Ph+ CML who were resistant to (n = 497) or intolerant of (n = 173) imatinib. The study randomly assigned 670 CML patients to one of four treatment arms: 100 mg once daily (n = 167), 50 mg twice daily (n = 168), 140 mg once daily (n = 167), or 70 mg twice daily (n=168). Efficacy was achieved across all dasatinib treatment groups, with the once-daily schedule demonstrating comparable efficacy (noninferiority) to the twice-daily schedule on the primary efficacy endpoint (the difference in the major cytogenetic response [MCyR]).

Seven years after the last patient was enrolled, 44% of the study subjects were known to be alive, and 31% had died. The remaining 25% had unknown survival data. Among the 167 patients treated with the 100-mg once-daily dosage of dasatinib, nine (5%) transformed to accelerated or blast-phase CML by 7 years while on treatment. At 2 years, MCyR was achieved by 63% of imatinib-resistant or -intolerant patients treated with dasatinib 100 mg once daily.

Dasatinib was first approved by the FDA in 2006 for the treatment of adults with CP Ph+ CML who are resistant or intolerant of prior therapy, including imatinib. At that time, dasatinib was also approved for adults with Ph+ acute lymphocytic leukemia (ALL) who are resistant to or intolerant of prior therapy. Dasatinib is the first BCR-ABL kinase inhibitor with survival data in its label for CP Ph+ CML patients who are resistant to or intolerant of imatinib.

Dasatinib is also an FDA-approved treatment for adults with newly diagnosed CP Ph+ CML (since October 2010).

Source: Bristol-Myers Squibb; August 13, 2015.

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