Following the phase 3 ENDEAVOR trial that compared 2 proteasome inhibitors-carfilzomib and bortezomib-in relapsed or refractory multiple myeloma patients, researchers conducted a second interim analysis to compare the overall survival between the 2 groups.
Following the phase 3 ENDEAVOR trial that compared 2 proteasome inhibitors—carfilzomib and bortezomib—in relapsed or refractory multiple myeloma patients, researchers conducted a second interim analysis to compare the overall survival between the 2 groups. The findings, published in Lancet Oncology, suggested that carfilzomib had significantly more meaningful improvements in survival.
The phase 3 ENDEAVOR trial recruited patients from 198 hospitals and outpatient clinics in 27 countries. The patients were adults with relapsed or refractory multiple myeloms, who had received between 1 and 3 previous lines of therapy. Each patient was randomly assigned to either the carfilzomib group or the bortezomib group.
“Historical trials that have shown an overall survival benefit in relapsed or refractory multiple myeloma have compared a doublet regimen to high-dose dexamethasone, which is not the current standard of care and is considered toxic,” the authors explained. “Additional multiple myeloma therapies that provide statistically significant and clinically meaningful improvements in overall survival in the relapsed or refractory setting are needed.”
The analysis was a log-rank test that was used to compare the overall survival of each study group. Following analysis of the 929 randomly assigned patients (464 in the carfilzomib group and 465 in the bortezomib group) the median overall survival was 47.6 months in the carfilzomib group, while the bortezomib group survival rate was 40 months. Grade 3 or worse adverse events occurred in 81% of the carfilzomib group and 71% of the bortezomib group, while 59% of patients in the carfilzomib group faced serious adverse events and 40% in bortezomib group.
Additionally, treatment-related deaths occurred in 5 (1%) of the 463 patients in the carfilzomib group and 2 (<1%) of the 456 patients in the bortezomib group had treatment-related deaths.
“To our knowledge, carfilzomib is the first and only multiple myeloma treatment that has been shown to extend overall survival in the relapsed setting over a current standard of care,” the researchers concluded. “On the basis of these results, carfilzomib combined with dexamethasone should be considered a standard of care for patients with relapsed or refractory multiple myeloma.”
Overall, the researchers found that carfilzomib demonstrated a significant and meaningful reduction in the risk of death and overall chance of survival. This analysis can be used in the decision process for which proteasome inhibitor to use for treating the disease.