Frontline Nilotinib Results In Superior Rates Of Molecular Response Versus Imatinib In Chinese Patients With Chronic Myeloid Leukemia In Chronic Phase (CML-CP): ENESTchina 12-Month Primary Analysis

Background In global clinical trials, nilotinib has shown superior efficacy vs imatinib for treating patients (pts) with CML-CP. The Evaluating Nilotinib Efficacy and Safety in Clinical Trials–China (ENESTchina) study is assessing the efficacy and safety of frontline nilotinib vs imatinib in Chinese pts with CML-CP. Methods ENESTchina (NCT01275196) is a multicenter, open-label, phase 3 study of Chinese adults with newly diagnosed (≤ 6 mo) CML-CP. Pts were randomized to nilotinib 300 mg BID (n = 134) or imatinib 400 mg QD (n = 133). The primary endpoint was the rate of major molecular response (MMR; ≤ 0.1% BCR-ABL on the international scale) at 12 mo. Molecular assessments were performed at a central laboratory. This analysis was conducted when all randomized pts had ≥ 12 mo of follow-up or discontinued early. Results Baseline characteristics were similar between the arms (Table). Most pts (nilotinib, 93%; imatinib, 95%) remained on treatment at the data cutoff. Median actual dose intensities were nilotinib 565 mg/day (range, 167-600 mg/day) and imatinib 393 mg/day (range, 204-550 mg/day). Sixteen pts (nilotinib, n = 9; imatinib, n = 7) discontinued, mainly due to adverse events (AEs; nilotinib, n = 3; imatinib, n = 1), withdrawal of consent (nilotinib, n = 3; imatinib, n = 1), or disease progression (nilotinib, n = 2; imatinib, n = 2). The primary endpoint was met, with a significantly higher rate of MMR at 12 mo in the nilotinib arm vs the imatinib arm (52% vs 28%, respectively; P Both drugs were well tolerated, with safety profiles similar to those reported in prior studies. The most common AEs on nilotinib were rash and myalgia; on imatinib, fluid retention and nasopharyngitis were most common (Table). One pt in the imatinib arm had a grade 1 increase in creatine phosphokinase-MB with no clinical signs indicative of ischemic heart disease. No cases of peripheral arterial occlusive disease, ischemic cerebrovascular events, or QTcF > 480 ms were observed in either arm. Newly occurring/worsening grade 3/4 thrombocytopenia and neutropenia occurred at similar rates in both arms, while leukopenia, lymphopenia, and anemia were more frequent in the imatinib arm. The most common newly occurring/worsening grade 3/4 biochemical abnormality in both arms was elevated lipase. Conclusions In Chinese pts with newly diagnosed CML-CP, nilotinib was well tolerated and demonstrated superior efficacy over imatinib, as shown by higher rates of MMR in all Sokal risk groups, despite similarly high rates of CCyR after 1 y with both drugs. These results highlight the utility of MMR as a more sensitive efficacy endpoint for differentiating tyrosine kinase inhibitors in pts with CML-CP and provide the first evidence-based, prospective confirmation of the superiority of nilotinib over imatinib observed in the ENESTnd trial. Disclosures: Wang: Novartis: Employment; Bristol Myers Squibb: Consultancy. Baccarani: Ariad: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Pfizer: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau. Jevtic: Novartis: Employment, Equity Ownership. Ortmann: Novartis: Employment. Yuan: Novartis: Employment. Menssen: Novartis: Employment. Saglio: ARIAD: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria.