Expanding Nilotinib Access in Clinical Trials (ENACT) study in adult patients with imatinib-resistant or -intolerant Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) in chronic phase (CP), accelerated phase (AP), or blast crisis (BC): Updated safety analysis

Abstract

7059 Background: Nilotinib, is a potent and highly selective oral inhibitor of BCR-ABL, approved in both the US and Europe for the treatment of patients (pts) with Ph+ CML-CP and -AP who are resistant or intolerant to prior therapy including imatinib. Methods: The ENACT study, which is ongoing, was initiated to provide expanded access to nilotinib and to obtain additional safety information in pts with imatinib-resistant or -intolerant CML-CP, -AP, or -BC. Pts received 400 mg nilotinib twice daily (BID). Dose escalation was not permitted. Pts who required dose reduction to 400 mg once daily due to toxicity were allowed to have a dose re-escalation to 400 mg BID after resolution of the adverse events (AEs) to grade 1, lack of response, or persistent disease at the investigator's discretion. Results: Results are available for the first 1056 of the more than 1400 currently enrolled pts (CP, n = 818; AP, n = 120; BC, n = 118). Median age of pts was 53 years, and 69% were imatinib-resistant. AE data are available for 974 pts. At data cutoff (June 30, 2007), 710 pts (67%) were continuing on nilotinib. Median duration of nilotinib exposure was 124 days for CP, 90 days for AP, and 54 days for BC. The main reasons for discontinuation were inadequate responses (13%) and AEs (11%). The majority of AEs were hematologic, with the most common grade 3/4 hematologic lab abnormalities being thrombocytopenia (22%) and neutropenia (13%). Non-hematologic AEs were mostly mild to moderate and included headache, rash, and nausea. Deaths were reported for 28 (3%) pts, and occurred more frequently among those with BC (n = 15). A low incidence of QT prolongation (QTcF > 500 msec, n = 2, 0.2%) was observed overall. Conclusions: This updated analysis of a large expanded access study further demonstrates that nilotinib is generally well tolerated in heavily pretreated pts in all phases of CML and shows no change in the safety profile of nilotinib in Ph+ CML. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Novartis Novartis Novartis