Date: 2017-06-23
Type of
information: Publication of results in a medical journal
phase: 3
Announcement: publication of results in The New English Journal of Medicine
Company: Novartis (Switzerland)
Product: Rydapt®(midostaurin)
Action
mechanism: kinase inhibitor. PKC412 (midostaurin) is an oral, multi-targeted kinase inhibitor in development for the treatment of patients with newly-diagnosed acute myeloid leukemia who are FLT3 mutation-positive, as detected by an FDA-approved test, and who are eligible to receive standard induction and consolidation chemotherapy. In order to help identify patients who may have a FLT3 mutation and potentially benefit from treatment with PKC412 (midostaurin), Novartis is collaborating with Invivoscribe Technologies for the development and FDA approval of the FLT3 companion diagnostic. The same test is being CE marked in Europe. Regulatory submissions for the companion diagnostic are being led by IVS.
Disease: newly diagnosed FLT3-mutated acute myeloid leukemia (AML)
Therapeutic
area: Cancer - Oncology
Country:
Trial
details: RATIFY, the largest clinical trial in FLT3-mutated AML to date, included 3,277 patients screened and 717 study participants from around the world.
Latest
news:
- • On June 23, 2017, Novartis announced that full results from the Rydapt® (midostaurin) Phase III RATIFY (CALGB 10603 [Alliance]) clinical trial were published in The New England Journal of Medicine (NEJM). Top-line data from this study were previously presented during the plenary session at the American Society of Hematology (ASH) Annual Meeting in 2015. New data include disease-free survival (DFS), further analysis of patients undergoing transplant and expanded safety information.
- In RATIFY, patients aged 18-59 years treated with Rydapt® in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation chemotherapy experienced significant improvement in overall survival (OS) with a 22% reduction in the risk of death compared with chemotherapy plus placebo. In patients in the Rydapt® arm, OS was 74.7 months [95% CI, 31.5-not reached] vs. 25.6 months [95% CI, 18.6-42.9] in the placebo arm (one-sided stratified log-rank p=0.009, HR=0.78). At four years, OS was 51.4% in the Rydapt® arm, compared with 44.3% in the placebo arm.
- The median event-free survival (EFS) was 8.2 months (95% CI, 5.4-10.7) in the Rydapt® arm and 3.0 months (95% CI, 1.9-5.9) in the placebo arm (one-sided stratified log-rank p=0.002, HR=0.78). Median DFS was greater with the addition of Rydapt® versus the placebo arm (26.7 months [95% CI, 19.4-not reached] vs. 15.5 months [95% CI, 11.3-23.5], respectively; p=0.01). The complete remission (CR) rate, defined as CR reported within 60 days of protocol therapy initiation, was 58.9% in the Rydapt arm and 53.5% in the placebo arm (p=0.15). The benefit of Rydapt on OS and EFS was consistent across all FMS-like tyrosine kinase 3 (FLT3) mutation subgroups, including internal tandem duplication (ITD) and tyrosine kinase domain (TKD) FLT3 mutations.
- More patients in the Rydapt® arm were able to undergo allogenic hematopoietic stem cell transplantation (HCT) during their first complete response versus placebo (28.1% vs. 22.7%, respectively; p=0.10). When censoring patients at the time of transplant (when protocol therapy was discontinued), OS was numerically better for those in the Rydapt arm versus placebo arm, with a 24.3% reduction in the risk of death at four years (63.7% vs. 55.7% respectively, p=0.08).
- The most frequent Grade 3 to 5 non-hematologic adverse events (AEs) (incidence greater than or equal to 20%) in the Rydapt arm were febrile neutropenia and infection. In the placebo arm, the most common AEs were febrile neutropenia, infection and lymphopenia. There were few significant differences (greater than 5%) observed in the overall rate of Grade 3 to 5 AEs between the treatment arms - patients receiving Rydapt® experienced higher rates of anemia and rash.
Is
general: Yes
