Expanding Nilotinib Access in Clinical Trials (ENACT)

BACKGROUND: Nilotinib is a selective, potent BCR‐ABL inhibitor. Previous studies demonstrated the efficacy and safety of nilotinib in Philadelphia chromosome‐positive chronic myeloid leukemia patients in chronic phase (CML‐CP) or accelerated phase who failed prior imatinib. METHODS: This expanded access trial further characterized the safety of nilotinib 400 mg twice daily in patients with CML‐CP (N = 1422). RESULTS: In this large, heavily pretreated population, nilotinib demonstrated significant efficacy, with complete hematologic response and complete cytogenetic response achieved in 43% and 34% of patients, respectively. Responses were rapid, mostly occurring within 6 months, and were higher in patients with suboptimal response to imatinib, with 75% and 50% achieving major cytogenetic response and complete cytogenetic response, respectively. At 18 months, the progression‐free survival rate was 80%. Most patients achieved planned dosing of 400 mg twice daily and maintained the dose >12 months. Nonhematologic adverse events (AEs) were mostly mild to moderate and included rash (28%), headache (25%), and nausea (17%). Grade 3 or 4 thrombocytopenia (22%), neutropenia (14%), and anemia (3%) were low and managed by dose reduction or brief interruption. Grade 3 or 4 elevations in serum bilirubin and lipase occurred in 4% and 7% of patients, respectively. The incidence of newly occurring AEs decreased over time. Of patients who experienced a dose reduction because of AEs and attempted a re‐escalation, 87% successfully achieved re‐escalation to the full dose. CONCLUSIONS: This large study confirms that nilotinib was well tolerated and that grade 3 or 4 AEs occurred infrequently and were manageable through transient dose interruptions. Cancer 2012;. © 2011 American Cancer Society. ENACT is the largest clinical study of patients with chronic myeloid leukemia in the chronic phase (N = 1422) who failed prior imatinib therapy because of resistance or intolerance. This study confirms the clinical efficacy and safety of nilotinib for the treatment of these patients, which was observed in the phase 2 registration study.