Amgen announced new results showing the positive overall survival (OS) findings from the final analysis of the Phase 3 ASPIRE trial. The study met the key secondary endpoint of OS, demonstrating that the addition of KYPROLIS (carfilzomib) to lenalidomide and dexamethasone (KRd) reduced the risk of death by 21 percent versus lenalidomide and dexamethasone alone (Rd) and extended survival by 7.9 months in patients with relapsed or refractory multiple myeloma (median OS 48.3 months for KRd versus 40.4 months for Rd, HR = 0.79, 95 percent CI, 0.67 – 0.95; p = 0.0045). These results were presented today during an oral presentation at the 59th American Society of Hematology (ASH) Annual Meeting & Exposition in Atlanta (ASH abstract #743).
“While significant advances have recently been made in treating relapsed or refractory multiple myeloma, most reported clinical trials have focused on how long a new treatment helps prevent recurrence of disease rather than on survival,” said Keith Stewart, M.B., Ch.B., Mayo Clinic in Arizona and principal investigator of the ASPIRE trial. “Results from the ASPIRE trial are among the first to show a significant overall survival advantage resulting from adding carfilzomib to lenalidomide and dexamethasone treatment in patients with relapsed or refractory multiple myeloma. The data support the early use of carfilzomib as an effective therapy at first relapse, regardless of prior treatment with Velcade or transplant.”
“KYPROLIS-based regimens are the first and only to demonstrate superior overall survival versus today’s standard of care in two Phase 3 studies and are resetting survival expectations for relapsed or refractory multiple myeloma patients,” said David Reese, M.D., senior vice president of Translational Sciences and Oncology at Amgen. “We are pleased with the KYPROLIS overall survival data presented at ASH this year as the results underscore our commitment to developing innovative treatment options to help cancer patients live longer.”
The final analysis of ASPIRE included subgroup analyses by prior lines of therapy, prior Velcade exposure at first relapse, and prior transplant at first relapse. Among these three groups, there was an 18 to 29 percent reduction in the risk of death for KRd versus Rd, consistent with findings in the overall population. Median OS was 11.4 months longer for KRd versus Rd in patients who had received one prior line of therapy (47.3 versus 35.9 months [HR = 0.81, 95 percent CI, 0.62 – 1.06]) and 6.5 months longer for patients with two or more prior lines (48.8 versus 42.3 months [HR = 0.79, 95 percent CI, 0.62 – 0.99]).
Notably the maximum OS improvement of 11 months was observed for patients at first relapse. This OS analysis supports the early use of KYPROLIS as effective therapy at first relapse, regardless of prior Velcade exposure or transplant. Patients treated with KRd reported improved global health status, with higher Global Health Status/Quality of Life (QoL) scores compared with Rd over 18 cycles of treatment (1‑sided p‑value = 0.0001) measured with the EORTC QLQ‑C30, an instrument validated in multiple myeloma.
Overall survival by Revised International Staging System (R-ISS) stage was also assessed. For R-ISS stage I (KRd, n = 42; Rd, n = 46), median OS was not reached for KRd and was 58 months for Rd (HR = 0.49, 95 percent CI, 0.26 – 0.92). For patients with R-ISS stage II (KRd, n = 194; Rd, n = 195), median OS was 45.4 months for KRd and 41.2 months for Rd (4.2 months; HR = 0.86, 95 percent CI, 0.68 – 1.10). For the small number of patients with R-ISS stage III (KRd, n = 37; Rd, n = 47), median OS was 23.3 months for KRd and 18.8 months for Rd (4.5 months; HR = 1.05, 95 percent CI, 0.66 – 1.68).
The safety data from ASPIRE was consistent with the known safety profile of KYPROLIS. The most common adverse events (greater than or equal to 20 percent) in the KYPROLIS arm were diarrhea, anemia, neutropenia, fatigue, upper respiratory tract infection, pyrexia, cough, hypokalemia, thrombocytopenia, muscle spasms, pneumonia, nasopharyngitis, nausea, constipation, insomnia and bronchitis.
Overall survival results from the Phase 3 ENDEAVOR head-to-head study of KYPROLIS plus dexamethasone (Kd) versus Velcade plus dexamethasone were also presented at ASH and showed that Kd was superior in extending survival across a variety of sub-group analyses of relapsed or refractory multiple myeloma patients, including age, prior line of therapy and previous exposure to Velcade (ASH abstract #1885, ASH abstract #1850).
The KRd and Kd regimens used in these trials are currently approved in the U.S., European Union and other countries based on primary analyses of progression-free survival (PFS) in the ASPIRE and ENDEAVOR studies, respectively. The KYPROLIS dosing used for ASPIRE (27 mg/m2; 10-minute infusion) and ENDEAVOR (56 mg/m2; 30-minute infusion) were optimized for each treatment regimen and are the currently approved doses for the KRd and Kd regimens, respectively.
Based on the ASPIRE results, Amgen has submitted a supplemental New Drug Application to the U.S. Food and Drug Administration to include the OS data from ASPIRE in the product information for KYPROLIS.
Filed Under: Drug Discovery
