Kyprolis Significantly Improved Survival of Relapsed Myeloma Patients in Phase 3 Study

Patients with relapsed or refractory multiple myeloma who receive a combination of Kyprolis (carfilzomib) and dexamethasone have significantly better survival rates than those receiving Velcade (bortezomib) plus dexamethasone, according to an interim analysis of the ENDEAVOR Phase 3 trial (NCT01568866).

The study met its primary endpoint, with patients on the Kyprolis arm living a median of 7.6 months longer than those on the Velcade combination. Detailed results were presented March 4 at the 16th International Myeloma Workshop in New Delhi.

A primary analysis of the trial, showing that Kyprolis increased the time to disease progression compared to Velcade, has already led to the approval of the Kyprolis plus dexamethasone combination for these patients in the U.S. and in the European Union.

“For an incurable disease like multiple myeloma, a major treatment goal for oncologists and hematologists is to help patients live as long as possible,” 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 a news release.

“Based on these data, we now know that Kyprolis not only significantly extended progression-free survival compared to Velcade, but also overall survival, making it a clinically meaningful advance in the treatment of relapsed or refractory multiple myeloma,” he said.

The ENDEAVOR trial is a randomized, open-label study designed to assess the safety and effectiveness of low-dose dexamethasone in combination with either Kyprolis or Velcade. The study enrolled 929 multiple myeloma patients who had relapsed after at least one but not more than three prior treatment regimens.

Primary endpoint was the time to disease progression or death, and secondary endpoints included overall survival, overall response rate, duration of response, and safety.

Results from a primary analysis, published in The Lancet Oncology, revealed that the progression-free survival of patients on the Kyprolis group — 18.7 months — nearly doubled that seen in the Velcade arm — 9.4 months. This led to the approval of Kyprolis in combination with low dose dexamethasone for multiple myeloma patients treated at least once.

Now, Amgen has revealed that those on the Kyprolis arm also live longer. While patients treated with Velcade had a median overall survival of 40 months, those on the Kyprolis arm lived a median of 47.6 months.

“These results confirm the superiority of Kyprolis over Velcade in relapsed or refractory multiple myeloma patients,” said Sean E. Harper, MD, executive vice president of research and development at Amgen.

“A survival benefit has rarely been demonstrated in relapsed or refractory multiple myeloma,” he said. “ENDEAVOR is the only study to demonstrate a survival benefit in a head-to-head comparison with a current standard of care regimen. These results further support Kyprolis as a foundational therapy in this patient population.”