The final overall survival results of the phase III ASPIRE trial indicate significant improvement with carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone (KRd) vs lenalidomide plus dexamethasone (Rd) in patients who had received one to three prior lines of therapy for multiple myeloma. The findings were reported in the Journal of Clinical Oncology by Siegel et al. Improved progression-free survival with the carfilzomib-containing regimen resulted in an expanded indication in this setting in 2015.
In the trial, 792 patients were randomized between July 2010 and March 2012 to receive KRd (n = 396) or Rd (n = 396) in 28-day cycles until withdrawal of consent, disease progression, or unacceptable toxicity; all patients received Rd only after 18 cycles. Prior analysis of progression-free survival, the primary endpoint, showed significant benefit of KRd (median = 26.3 vs 17.6 months, hazard ratio [HR] = 0.69, P < .001).
Median follow-up for overall survival was 67.1 months. Median overall survival was 48.3 months in the KRd group vs 40.4 months in the Rd group (hazard ratio [HR] = 0.79, P = .0045). Median overall survival was 47.3 vs 35.9 months among patients receiving 1 prior line of therapy (184 in KRd group and 157 in Rd group; HR = 0.81, 95% confidence interval [CI] = 0.62–1.06) and 48.8 vs 42.3 months among those receiving at least 2 prior lines of therapy (HR = 0.79, 95% CI = 0.62–0.99).
Grade ≥ 3 adverse events occurred in 87% of the KRd group vs 83% of the Rd group. Adverse events led to treatment discontinuation in 19.9% vs 21.5%. Grade ≥ 3 adverse events of interest included acute renal failure (3.8% vs 3.3%), cardiac failure (4.3% vs 2.1%), ischemic heart disease (3.8% vs 2.3%), hypertension (6.4% vs 2.3%), thrombocytopenia (20.2% vs 14.9%), and peripheral neuropathy (2.8% vs 3.1%).
The investigators concluded, “KRd demonstrated a statistically significant and clinically meaningful reduction in the risk of death vs Rd, improving survival by 7.9 months. The KRd efficacy advantage is most pronounced at first relapse.”
The study was supported by Onyx Pharmaceuticals, an Amgen subsidiary, and by Amgen.
David S. Siegel, MD, PhD, of the John Theurer Cancer Center, Hackensack University Medical Center, is the corresponding author for the Journal of Clinical Oncology article.
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