title: A pooled analysis of overall survival in COMFORT-I and COMFORT-II, 2 randomized phase III trials of ruxolitinib for the treatment of myelofibrosis.
abstract: Ruxolitinib, a potent Janus kinase 1/2 inhibitor, resulted in rapid and durable improvements in splenomegaly and disease-related symptoms in the 2 phase III COMFORT studies. In addition, ruxolitinib was associated with prolonged survival compared with placebo (COMFORT-I) and best available therapy (COMFORT-II). We present a pooled analysis of overall survival in the COMFORT studies using an intent-to-treat analysis and an analysis correcting for crossover in the control arms. Overall, 301 patients received ruxolitinib (COMFORT-I, n=155; COMFORT-II, n=146) and 227 patients received placebo (n=154) or best available therapy (n=73). After a median three years of follow up, intent-to-treat analysis showed that patients who received ruxolitinib had prolonged survival compared with patients who received placebo or best available therapy [hazard ratio=0.65; 95% confidence interval (95%CI): 0.46-0.90; P=0.01]; the crossover-corrected hazard ratio was 0.29 (95%CI: 0.13-0.63). Both patients with intermediate-2- or high-risk disease showed prolonged survival, and patients with high-risk disease in the ruxolitinib group had survival similar to that of patients with intermediate-2-risk disease in the control group. The Kaplan-Meier estimate of overall survival at week 144 was 78% in the ruxolitinib arm, 61% in the intent-to-treat control arm, and 31% in the crossover-adjusted control arm. While larger spleen size at baseline was prognostic for shortened survival, reductions in spleen size with ruxolitinib treatment correlated with longer survival. These findings are consistent with previous reports and support that ruxolitinib offers a survival benefit for patients with myelofibrosis compared with conventional therapies. (clinicaltrials.gov identifiers: COMFORT-I, NCT00952289; COMFORT-II, NCT00934544).
authors.affiliation: University of Florence, Italy amvannucchi@unifi.it.
authors.forename: Alessandro M
authors.initials: AM
authors.lastname: Vannucchi
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.affiliation: Hôpital Saint-Louis et Université Paris Diderot, Paris, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Kiladjian
authors.affiliation: Stanford Cancer Institute, CA, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Gotlib
authors.affiliation: Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Cervantes
authors.affiliation: Mayo Clinic, Scottsdale, AZ, USA.
authors.forename: Ruben A
authors.initials: RA
authors.lastname: Mesa
authors.affiliation: Incyte Corporation, Wilmington, DE, USA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Sarlis
authors.affiliation: Incyte Corporation, Wilmington, DE, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Peng
authors.affiliation: Incyte Corporation, Wilmington, DE, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Sandor
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Prashanth
authors.initials: P
authors.lastname: Gopalakrishna
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Abdel
authors.initials: A
authors.lastname: Hmissi
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Viktoriya
authors.initials: V
authors.lastname: Stalbovskaya
authors.affiliation: Princess Margaret Cancer Center, University of Toronto, Ontario, Canada.
authors.forename: Vikas
authors.initials: V
authors.lastname: Gupta
authors.affiliation: Guy's and St. Thomas' NHS Foundation Trust, Guy's Hospital, London, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Harrison
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053613:Janus Kinase 1 / Q000037:antagonists & inhibitors*; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D055728:Primary Myelofibrosis / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality*; D011720:Pyrazoles / Q000008:administration & dosage*; D011743:Pyrimidines; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D009570:Nitriles; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib; C507904:JAK1 protein, human; C507924:JAK2 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2