Kyprolis (carfilzomib) plus dexamethasone improved overall survival for patients with relapsed or refractory multiple myeloma.
Overall survival (OS) was improved by 21 percent in patients with relapsed or refractory multiple myeloma who were on Kyprolis (carfilzomib) plus dexamethasone rather than dexamethasone plus Velcade (bortezomib), according to results of the phase 3 ENDEAVOR trial announced by Amgen.
The median OS was 47.6 months in the Kyprolis arm versus 40.0 months in Velcade arm. The safety data were consistent with previously reported study outcomes. The full updated results from the trial will be presented at the 16th International Myeloma Workshop, which is being held in New Delhi from March 1 to 4, 2017.
"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, M.D., professor of Clinical Therapeutics at the National and Kapodistrian University of Athens, School of Medicine said in a statement. "Based on these data, we now know that Kyprolis not only significantly extended progression-free survival (PFS)compared to Velcade, but also OS, making it a clinically meaningful advance in the treatment of relapsed or refractory multiple myeloma."
The phase 3 ENDEAVOR study randomized 929 patients to receive Kyprolis as a 30-minute infusion along with dexamethasone (464 patients) or Velcade and dexamethasone (465 patients). Kyprolis was administered at a starting dose of 20 mg/m2 on days one and two of cycle. If tolerated, the dose was escalated to 56 mg/m2 on day eight of cycle one. After this point, the 56 mg/m2 dose was maintained on days nine, 15 and 16 and throughout subsequent cycles. In the control arm, patients received Velcade at 1.3 mg/m2. The majority of patients received Velcade subcutaneously (75 percent).
The median age of patients enrolled in the trial was 65 years. All but 7 percent of patients had ECOG PS of 0 or 1 (about 50 percent ECOG 0), and about 20 percent of the patients had high-risk cytogenetic by fluorescence in situ hybridization. The primary endpoint was PFS, with OS, objective response rate (ORR), duration of response and safety as secondary measures.
Kyprolis and dexamethasone reduced the risk of progression by 47 percent compared with Velcade and dexamethasone. The median PFS with Kyprolis was 18.7 versus 9.4 months with Velcade. The advantage in PFS seen with Kyprolis was consistent across subgroups.
The ORR was 77 percent with Kyprolis versus 63 percent with Velcade. The complete response rate with Kyprolis was 13 percent versus 6 percent with Velcade. The rate of very good partial response or better with Kyprolis was 54 percent compared with 29 percent with Velcade.
Grade 3 adverse events (AEs) occurred more frequently in the Kyprolis arm compared with Velcade (73 percent vs 67 percent). Additionally, serious AEs were more common with Kyprolis (48 percent vs 36 percent). However, dose reductions associated with AEs were more frequent with Velcade versus Kyprolis (48 percent vs 23 percent). Treatment discontinuation due to AEs and on-study deaths were comparable between the two arms.
Grade 3 or higher hematologic adverse events occurred in a similar proportion of patients in both groups, including anemia, thrombocytopenia, neutropenia, upper respiratory infection and pneumonia. However, there was an increase in the incidence of hypertension and dyspnea with Kyprolis versus Velcade. The most frequent non-hematologic grade 3 or higher AEs were diarrhea, fatigue, dyspnea, pyrexia, constipation and insomnia.
Peripheral neuropathy occurred in 5 percent of patients treated with Velcade and 1.3 percent of those in the Kyprolis arm. The proportion of patients with grade 2 or higher peripheral neuropathy was significantly higher with Velcade (32 percent versus 6 percent).
Commenting on the ENDEAVOR update, Sean E. Harper, M.D., executive vice president of Research and Development at Amgen, said, “These results confirm the superiority of Kyprolis over Velcade in relapsed or refractory multiple myeloma patients," said "A survival benefit has rarely been demonstrated in relapsed or refractory multiple myeloma. 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.”