Date: 2011-12-13
Type of information:
phase: 3
Announcement: results
Company: Novartis (Switzerland)
Product: INC424 (ruxolitinib)
Action mechanism: INC424 is an oral inhibitor of the JAK1 and JAK2 tyrosine kinases.
Disease: myelofibrosis
Therapeutic area: Cancer - Oncology - Blood diseases
Country: Europe, USA, Canada, Australia
Trial
details: COMFORT-II Predictors of Response and Post-Hoc HRQoL Study Details The COMFORT-II study included an assessment of HRQoL and myelofibrosis symptoms using validated instruments, including the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym). Scores from these instruments were measured at baseline and weeks 8, 16, 24 and 48. A total of 219 patients were included in two treatment groups: INC424 (n=146) and BAT (n=73). Based on a detailed analysis of the patterns of change of QoL scales over time, and compared with the BAT arm, INC424-treated patients experienced significant improvement in Global Health Status/QoL and in symptoms measured by the FACT-Lym symptom subscale including pain, swelling, fever, night sweats, itching, trouble sleeping, fatigue, weight loss, loss of appetite and trouble concentrating compared to BAT. In addition, the EORTC QLQ-30 showed that treatment differences in physical functioning, role functioning, fatigue and appetite loss were significantly better for INC424-treated patients as early as week 8 (p<0.05), and this effect was sustained throughout 48 weeks (p<0.05). The COMFORT-II trial was conducted by Novartis in Europe.
A detailed analysis of predictors of spleen response in various patient subsets indicated that INC424 was more effective than BAT for all patient subgroups. In particular, responses to INC424 occurred and were superior to BAT regardless of the JAK2 mutation status.
Latest
news: Novartis has announced additional results from two pivotal Phase III trials evaluating Janus kinase (JAK) inhibitor INC424 (ruxolitinib) in myelofibrosis. These data demonstrate the important potential role of INC424 in treating patients with myelofibrosis, a life-threatening blood cancer characterized by bone marrow failure, enlarged spleen (splenomegaly) and debilitating symptoms. Results are being presented at the 53rd Annual Meeting of the American Society of Hematology (ASH) in San Diego. A post-hoc analysis from the COMFORT-II (COntrolled MyeloFibrosis Study with ORal JAK Inhibitor Therapy) study evaluated patient-reported health-related quality of life (HRQoL) measures for INC424 versus best available therapy (BAT). The results showed a substantial improvement in HRQoL and myelofibrosis symptoms compared with baseline for patients receiving INC424 but remained the same or worsened for patients receiving BAT. Results were based on a broad range of validated QoL instruments. In the second Phase III study, COMFORT-I researchers evaluated INC424 versus placebo in symptom improvement and spleen volume reduction, as well as overall survival. Results showed that patients receiving INC424 had higher response rates based on reductions in spleen volume and Total Symptom Score (TSS). The TSS evaluated changes in symptoms, such as abdominal discomfort, pain under the ribs on the left side, early satiety, itching, night sweats and bone or muscle pain. These benefits were consistent across all patient subgroups, including myelofibrosis disease subtype, age, risk group, presence or absence of JAK2 mutation, hemoglobin, spleen size and TSS. In the COMFORT-I updated analysis, INC424 also demonstrated an overall survival advantage over placebo. A total of 13 INC424 and 24 placebo patients died during the study or during extended follow up after median follow up of 51 and 52 weeks, respectively, representing a hazard ratio (95% CI) of 0.499 (0.254, 0.98) (p=0.0395). Survival was estimated by the Kaplan-Meier method.
