Adding the proteasome inhibitor Kyprolis (carfilzomib) to the standard regimen of Revlimid (lenalidomide) and dexamethasone reduced the risk of death in patients with relapsed multiple myeloma by 21%, according to results from the final analysis of the Phase 3 ASPIRE trial (NCT01080391).
Proteasomes break down proteins in cells for degradation and recycling. As a proteasome inhibitor, Kyprolis causes cancer cell death by prompting an excessively high amount of abnormal proteins. Kyprolis has shown to be especially effective at causing the death of myeloma cells.
In the international ASPIRE trial, researchers sponsored by Amgen evaluated the effectiveness of Kyprolis when administered with Revlimid and dexamethasone in treating patients with relapsed multiple myeloma, compared with treatment by Revlimid and dexamethasone alone.
The trial included 792 patients who had relapsed multiple myeloma after being treated with one to three prior regimens. The trial was conducted in the United States, Europe, and Israel.
ASPIRE’s primary endpoint was progression-free survival, or the time to disease progression or death, while secondary endpoints included overall survival (OS), duration of response, disease-control rate, quality of life, and safety.
Results from this clinical trial have shown that the Kyprolis combo led to a reduction in the risk of death by 21% compared to Revlimid and dexamethasone alone. The median OS was 48.3 months for patients in the Kyprolis arm, compared to 40.4 months for patients in the control group.
“For multiple myeloma patients, the first relapse is usually the most devastating,” David S. Siegel, MD, PhD, chief of the Multiple Myeloma Division at John Theurer Cancer Center and ASPIRE trial researcher, said in a press release. “These data clearly show that the addition of Kyprolis – for just 18 cycles – to lenalidomide and dexamethasone at relapse gave patients a significantly improved chance of survival. With these results, this Kyprolis regimen should be considered a new standard of care.”
The most common adverse events reported in the trial included diarrhea, anemia, neutropenia, fatigue, upper respiratory tract infection, fever, cough, low potassium levels, low platelet numbers, muscle spasms, pneumonia, nasopharyngitis, nausea, constipation, insomnia, and bronchitis.
Previous results from the ASPIRE study that showed significant improvement in progression-free survival led to Kyprolis’ approval in the United States, Europe, and other countries.
Results from another clinical trial sponsored by Amgen, the Phase 3 ENDEAVOR trial (NCT01568866), showed that the administration of Kyprolis with dexamethasone better reduces the risk of death and leads to longer overall survival for relapsing multiple myeloma patients than a regimen of Velcade (bortezomib) and dexamethasone.
“The ENDEAVOR study has already demonstrated that Kyprolis is the superior proteasome inhibitor versus Velcade,” said Sean E. Harper, MD, executive vice president of research and development at Amgen. “This overall survival benefit from the ASPIRE trial further supports the importance of proteasome inhibition and duration of treatment with Kyprolis in the treatment of relapsed multiple myeloma.”