Relapsed multiple myeloma patients who receive Kyprolis (carfilzomib) plus dexamethasone as their second-to-fourth treatment regimen survive a median of 7.6 months longer than those given Velcade (bortezomib) and dexamethasone, new data from the ENDEAVOR trial (NCT01568866) has shown.
In a head-to-head comparison, the ENDEAVOR study is the first Phase 3 clinical trial to compare two proteasome inhibitors and to show extended overall survival over a current standard of care for relapsed patients.
This has led the U.S. Food and Drug Administration to accept for review Amgen‘s supplemental new drug application of Kyprolis for this indication. The decision is expected by April 30, 2018, the company announced in a press release.
The results of this study, “Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial,” were published in Lancet Oncology.
“These results showed Kyprolis and dexamethasone significantly reduced the risk of death compared to Velcade and dexamethasone in patients with relapsed or refractory multiple myeloma,” study co-author and investigator Meletios A. Dimopoulos, MD, professor of Clinical Therapeutics at the National and Kapodistrian University of Athens, School of Medicine, said in another press release. “These results support the use of Kyprolis and dexamethasone as a standard of care for multiple myeloma patients at first relapse.”
Both Kyprolis and Velcade are proteasome inhibitors. The proteasome plays an important role in the turnover and breakdown of proteins when they are malfunctioning or worn out. When the proteasome is inhibited, this can lead to an accumulation of damaged proteins that can trigger cell death. Proteasome inhibitors have been shown to be particularly effective for the treatment of myeloma because these cancer cells contain higher amounts of abnormal proteins.
The randomized ENDEAVOR trial included 929 patients with relapsed multiple myeloma. Half of them were assigned to receive Kyprolis plus dexamethasone, while the other half of patients received Velcade plus dexamethasone.
In a prior update, published in The Lancet Oncology, researchers showed that the Kyprolis combo increased the time to disease progression or death from 9.4 months to 18.7 months, with the trial meeting its primary goal. Now, the authors of the study show that treatment with Kyprolis also can improve overall survival.
The median overall survival for Kyprolis-treated patients was 47.6 months, and 40.0 months for those in the Velcade arm, representing an improvement of 7.6 months. This finding is of significance because “few clinical trials have demonstrated overall survival benefits in patients with relapsed or refractory multiple myeloma,” said Sean E. Harper, MD, executive vice president of Research and Development at Amgen.
Although more serious adverse events were seen in the Kyprolis group, this most likely could be because treatment time was longer for this drug than for Velcade. Correcting for exposure, no significant differences in adverse events were reported. The most common adverse events in the Kyprolis arm included anemia, diarrhea, fatigue, hypertension, cough, insomnia, upper respiratory tract infection, peripheral edema, nausea, bronchitis, back pain, low platelet levels, and headache.
These results show that Kyprolis in combination with dexamethasone is an effective treatment for relapsed or refractory multiple myeloma, and should be considered standard of care.