Amgen and its subsidiary Onyx Pharmaceuticals, Inc., results of the Phase 3 ASPIRE (CArfilzomib, Lenalidomide, and DexamethaSone versus Lenalidomide and Dexamethasone for the treatment of PatIents with Relapsed Multiple Myeloma) trial, which evaluated Kyprolis (carfilzomib) for Injection plus Revlimid (lenalidomide) and dexamethasone (KRd) compared with Revlimid and dexamethasone (Rd) in patients with relapsed multiple myeloma. As previously reported, the ASPIRE study met its primary endpoint by demonstrating that KRd significantly extended the time patients lived without their disease worsening, or progression-free survival (PFS), by 26.3 months compared to 17.6 months with Rd (HR=0.69; 95 percent CI: 0.57-0.83; p<0.0001), an 8.7 month improvement in PFS.
The results from ASPIRE (abstract 79) will be featured during the 56th American Society of Hematology (ASH) Annual Meeting and Exposition press briefing on Saturday, December 6 at 8 a.m. PT and were published in the New England Journal of Medicine. Keith Stewart, M.B., Ch.B., dean for research at Mayo Clinic in Arizona and principal investigator will present these results in an oral session at ASH on Sunday, December 7 at 12 p.m. PT.
Secondary endpoints, which are being presented for the first time, included overall survival (OS), overall response rate (ORR), duration of response (DOR), health-related quality of life (HR-QoL) measures and safety. While the data for median OS are not yet mature based on the prespecified statistical boundary at the interim (p=0.005), the analysis showed a trend in favor of KRd compared with Rd ()p=0.018, two-sided p=0.04). Patients will continue to be monitored for OS. The ORR was 87.1 percent with KRd and 66.7 percent with Rd ()p<0.0001, two-sided p<0.001). In the KRd and Rd groups, 14 percent versus 4.3 percent of patients achieved a stringent complete response, a measurement indicating superior depth of response. Median DOR was 28.6 months (KRd) and 21.2 months (Rd). KRd consistently improved Global HR-QoL compared with Rd over 18 cycles of treatment (one-sided p=0.0001, two-sided p<0.001).
“Nearly all patients with multiple myeloma experience a relapse following treatment, underscoring the need for new options that not only extend the time patients live without their disease progressing, but also improve the depth and duration of a response to treatment,” said Dr. Stewart. “The combination of carfilzomib, lenalidomide and low-dose dexamethasone generates deep and durable responses, provides a clinically meaningful improvement in progression-free survival and promises to be an important advancement in the treatment of myeloma.”
Treatment discontinuation due to an adverse event (AE) occurred in 15.3 percent (KRd) versus 17.7 percent (Rd) of patients. In the KRd arm, 7.7 percent versus 8.5 percent (Rd) of patients died while still on study treatment or within 30 days of receiving the last dose of study treatment. The most common hematologic treatment-emergent AEs (≥grade 3) included neutropenia (29.6 percent [KRd] versus 26.5 percent [Rd]), anemia (17.9 percent [KRd] versus 17.2 percent [Rd]) and thrombocytopenia (16.6 percent [KRd] versus 12.3 percent [Rd]). The most common nonhematologic treatment-emergent AEs (≥grade 3) included hypokalemia (9.4 percent [KRd] versus 4.9 percent [Rd]), fatigue (7.7 percent [KRd] versus 6.4 percent [Rd]) and diarrhea (3.8 percent [KRd] versus 4.1 percent [Rd]). Other treatment-emergent AEs of interest (all grade) included dyspnea (19.4 percent [KRd] versus 14.9 percent [Rd]), hypertension (14.3 percent [KRd] versus 6.9 percent [Rd]), acute renal failure (grouped term:8.4 percent [KRd] versus 7.2 percent [Rd]), cardiac failure (grouped term:6.4 percent [KRd] versus 4.1 percent [Rd]) and ischemic heart disease (5.9 percent [KRd] versus 4.6 percent [Rd]). Lastly, rates of peripheral neuropathy (grouped term) were 17.1 percent (KRd) and 17.0 percent (Rd), respectively.
“Delivering new potential treatment options exemplifies Onyx and Amgen’s commitment to advancing the care of patients with multiple myeloma,” said Pablo J. Cagnoni, M.D., president, Onyx Pharmaceuticals, Inc. “The results from the Phase 3 ASPIRE study bring us one step closer to establishing Kyprolis as a backbone of therapy in the treatment of multiple myeloma.”
Results from the ASPIRE trial will form the basis for regulatory submissions throughout the world beginning in the first half of 2015. In the U.S., the data may support the conversion of accelerated approval to full approval and expand the current indication.