title: Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial.
abstract: In the phase 3 Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients (ENESTnd) study, nilotinib resulted in earlier and higher response rates and a lower risk of progression to accelerated phase/blast crisis (AP/BC) than imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP). Here, patients' long-term outcomes in ENESTnd are evaluated after a minimum follow-up of 5 years. By 5 years, more than half of all patients in each nilotinib arm (300 mg twice daily, 54%; 400 mg twice daily, 52%) achieved a molecular response 4.5 (MR(4.5); BCR-ABL⩽0.0032% on the International Scale) compared with 31% of patients in the imatinib arm. A benefit of nilotinib was observed across all Sokal risk groups. Overall, safety results remained consistent with those from previous reports. Numerically more cardiovascular events (CVEs) occurred in patients receiving nilotinib vs imatinib, and elevations in blood cholesterol and glucose levels were also more frequent with nilotinib. In contrast to the high mortality rate associated with CML progression, few deaths in any arm were associated with CVEs, infections or pulmonary diseases. These long-term results support the positive benefit-risk profile of frontline nilotinib 300 mg twice daily in patients with CML-CP.
authors.affiliation: Abteilung Hämatologie/Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Hochhaus
authors.affiliation: Division of Internal Medicine & Hematology, University of Turin, Orbassano, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Saglio
authors.affiliation: South Australian Health and Medical Research Institute (SAHMRI), University of Adelaide, SA Pathology, Adelaide, South Australia, Australia.
authors.forename: T P
authors.initials: TP
authors.lastname: Hughes
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Larson
authors.affiliation: Leukemia Research Institute, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: D-W
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: S
authors.initials: S
authors.lastname: Issaragrisil
authors.affiliation: Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: P D
authors.initials: PD
authors.lastname: le Coutre
authors.affiliation: Centre Régional de Lutte Contre le Cancer de Bordeaux et du Sud-Ouest, Institut Bergonié, Département d'Oncologie Médicale, Bordeaux, France.
authors.forename: G
authors.initials: G
authors.lastname: Etienne
authors.affiliation: Hospital das Clinicas FMUSP, São Paulo, Brazil.
authors.forename: P E
authors.initials: PE
authors.lastname: Dorlhiac-Llacer
authors.affiliation: Royal Liverpool University Hospital, Liverpool, UK.
authors.forename: R E
authors.initials: RE
authors.lastname: Clark
authors.affiliation: Sarah Cannon Research Institute, Nashville, TN, USA.
authors.forename: I W
authors.initials: IW
authors.lastname: Flinn
authors.affiliation: Department of Hematology, Osaka City University, Osaka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nakamae
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: B
authors.initials: B
authors.lastname: Donohue
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: W
authors.initials: W
authors.lastname: Deng
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: D
authors.initials: D
authors.lastname: Dalal
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: H D
authors.initials: HD
authors.lastname: Menssen
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: H M
authors.initials: HM
authors.lastname: Kantarjian
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate / Q000008:administration & dosage* / Q000494:pharmacology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D015466:Leukemia, Myeloid, Chronic-Phase / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D011743:Pyrimidines / Q000008:administration & dosage* / Q000494:pharmacology; D018570:Risk Assessment; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D002784:Cholesterol; C498826:nilotinib
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