title: The clinical benefit of ruxolitinib across patient subgroups: analysis of a placebo-controlled, Phase III study in patients with myelofibrosis.
abstract: Myelofibrosis (MF) patients can present with a wide spectrum of disease characteristics. We analysed the consistency of ruxolitinib efficacy across patient subgroups in the COntrolled MyeloFibrosis Study With ORal JAK Inhibitor Treatment (COMFORT-I,) a double-blind trial, where patients with intermediate-2 or high-risk MF were randomized to twice-daily oral ruxolitinib (n = 155) or placebo (n = 154). Subgroups analysed included MF subtype (primary, post-polycythaemia vera, post-essential thrombocythaemia), age (≤65, > 65 years), International Prognostic Scoring System risk group, baseline Eastern Cooperative Oncology Group performance status (0, 1, ≥2), JAK2 V617F mutation (positive, negative), baseline haemoglobin level (≥100, <100 g/l), baseline platelet count (100-200 × 10(9)/l, >200 × 10(9)/l), baseline palpable spleen size (≤10, >10 cm), and baseline quartile of spleen volume and Total Symptom Score (TSS; Q1 = lowest, Q4 = highest). Mean percentage change from baseline to week 24 in spleen volume and TSS were calculated for ruxolitinib and placebo in each subgroup. Overall survival was estimated by Kaplan-Meier method according to original randomization group. In ruxolitinib-treated patients, reductions in spleen volume and TSS and evidence of improved survival relative to placebo across subgroups were consistent with those seen in the COMFORT-I population, confirming that ruxolitinib is an effective therapy for the spectrum of MF patients studied in COMFORT-I.
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. sverstov@mdanderson.org
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Ruben A
authors.initials: RA
authors.lastname: Mesa
authors.forename: Jason
authors.initials: J
authors.lastname: Gotlib
authors.forename: Richard S
authors.initials: RS
authors.lastname: Levy
authors.forename: Vikas
authors.initials: V
authors.lastname: Gupta
authors.forename: John F
authors.initials: JF
authors.lastname: DiPersio
authors.forename: John V
authors.initials: JV
authors.lastname: Catalano
authors.forename: Michael
authors.initials: M
authors.lastname: Deininger
authors.forename: Carole
authors.initials: C
authors.lastname: Miller
authors.forename: Richard T
authors.initials: RT
authors.lastname: Silver
authors.forename: Moshe
authors.initials: M
authors.lastname: Talpaz
authors.forename: Elliott F
authors.initials: EF
authors.lastname: Winton
authors.forename: Jimmie H
authors.initials: JH
authors.lastname: Harvey
authors.forename: Murat O
authors.initials: MO
authors.lastname: Arcasoy
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hexner
authors.forename: Roger M
authors.initials: RM
authors.lastname: Lyons
authors.forename: Ronald
authors.initials: R
authors.lastname: Paquette
authors.forename: Azra
authors.initials: A
authors.lastname: Raza
authors.forename: Kris
authors.initials: K
authors.lastname: Vaddi
authors.forename: Susan
authors.initials: S
authors.lastname: Erickson-Viitanen
authors.forename: William
authors.initials: W
authors.lastname: Sun
authors.forename: Victor
authors.initials: V
authors.lastname: Sandor
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D009570:Nitriles; D009929:Organ Size; D055728:Primary Myelofibrosis / Q000188:drug therapy* / Q000401:mortality; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D011720:Pyrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D011743:Pyrimidines; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib