Updated Results of Ruxolitinib Phase 3 Trials Show Significant Overall Survival Advantage

San Diego—An updated analysis of two phase 3 trials found that ruxolitinib had a significant overall survival advantage across a variety of subgroups and that the oral drug was associated with improvement in health-related quality of life and myelofibrosis symptoms. The findings were presented in oral abstract sessions at the ASH meeting. In November, the US Food and Drug Administration approved ruxolitinib as the first drug to treat intermediate- or high-risk myelofibrosis. Ruxolitinib, an oral Janus kinase 1 (JAK1) and JAK2 inhibitor, was granted orphan drug status. COMFORT (Controlled Myelofibrosis Study with Oral JAK Inhibitor Therapy)-I was the largest study for patients with myelofibrosis, a life-threatening blood cancer affecting approximately 16,000 to 18,500 people in the United States. Srdan Verstovsek, MD, PhD, the study’s lead author, presented the results of the randomized, double-blind, placebo-controlled trial. Dr. Verstovsek is an associate professor in the department of leukemia at the University of Texas MD Anderson Cancer Center in Houston. He said that 13 patients in the ruxolitinib group and 24 patients in the placebo group died during the study or during the follow-up period, which was a median of 51 weeks (hazard ratio, 0.499; 95% confidence interval, 0.25-0.98; P=.0395). The authors randomized 309 patients in the United States, Canada, and Australia to receive 15 to 20 mg of ruxolitinib or placebo twice daily: 155 were in the ruxolitinib group and 154 were in the placebo group. Demographics were similar between the groups. The primary end points were the percent change from baseline to week 24 in spleen volume and total symptom score based on disease subtype, age, international prognostic scoring system risk group, presence or absence of the JAK2 V617F mutation, baseline hemoglobin level, baseline palpable spleen length, and baseline total symptom score. According to Dr. Verstovsek, patients rated the severity of symptoms in the past 24 hours on a 0 (absent) to 10 (worst imaginable) scale. Symptoms included night sweats, pruritus, abdominal discomfort, bone or muscle pain, and inactivity. The authors calculated the total symptom score as the sum of the individual scores except for inactivity. Dr. Verstovsek said that after 24 weeks of treatment, patients taking ruxolitinib had higher response rates in terms of reduced spleen volume and total symptom score, and the results were consistent across all subgroups. Of the 154 patients in the placebo group, 152 crossed over to the ruxolitinib group, which was allowed if they experienced spleen progression or worsening symptoms. The median time to crossover was 41.1 weeks. Eleven percent of patients in each group withdrew because of side effects. When the patients had their treatment interrupted, the symptoms returned to baseline after 7 to 10 days, but the symptoms did not get worse than they were at baseline, according to Dr. Verstovsek. In COMFORT-II, the authors randomized 219 patients in a 2:1 ratio to receive 15 or 20 mg of ruxolitinib (n=146) or best available therapy (n=73). Patients with progressive disease could cross over to the ruxolitinib group. Claire N. Harrison, DM, FRCP, the study’s lead author, presented the results. Compared with the best available therapy group, patients receiving ruxolitinib had significant improvement in global health status/quality of life and symptoms such as pain, swelling, fever, night sweats, itching, trouble sleeping, fatigue, and weight loss. Of the patients taking ruxolitinib, 28.5% had a ≥35% reduction in spleen volume compared with none of the patients in the best available therapy group (P<.0001). According to the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 measurement, patients in the ruxolitinib group had better scores for physical functioning, role functioning, fatigue, and appetite loss compared with the best available therapy group beginning at week 8 and continuing through week 48 (P<.05).