ASH 2015: Investigators update results on key carfilzomib studies: ENDEAVOR and ASPIRE

by Thomas R. Collins: A subgroup analysis of data from the ENDEAVOR trial, comparing carfilzomib and dexamethasone (Kd) to bortezomib and dexamethasone (Vd) — shows improved progression-free survival (PFS) on Kd, whether patients had been treated with just one prior line of therapy or with two or more.

The data — presented at the 57^th Annual Meeting of the American Society of Hematology — also shows markedly better PFS in the 1-prior-line arm than the at-least-2-prior-lines arm, said Philippe Moreau, MD, Head of Hematology at University Hospital in Nantes, France.

Carfilzomib, a proteasome inhibitor, was approved in Europe in November for use in combination with lenalidomide and dexamethasone in multiple myeloma patients who have received at least one prior line of therapy.

The subgroup analysis in the 929-patient ENDEAVOR trial¹ shows a median PFS of 22.2 months in the 1-prior-line segment of the Kd arm, compared to 10.1 for that group in the Vd arm. Among those with more prior lines of therapy, median PFS was 14.9 months for Kd, and 8.4 for Vd.

The Kd arm also showed, regardless of 1 prior line or at least 2 prior lines, significant improvements over Vd in complete response, very good partial response and overall response, investigators found.

A trade-off with Kd might be safety concerns. Some adverse events, including hypertension and cardiac failure, were higher in the Kd arm than the Vd arm for all patients. Patients in the Kd arm were three times as likely to experience Grade 3 or worse hypertension (8.9% vs. 2.6%), and three times as likely to experience Grade 3 or worse cardiac failure (2.2% vs. 0.7%).

In a new analysis of another highly-followed trial, the 792-patient pivotal Phase 3 ASPIRE trial², comparing carfilzomib plus lenalidomide and dexamethasone (KRd) to lenalidomide and dexamethasone alone (Rd), continues to show consistent benefit of KRd in both patients with high-risk and standard cytogenetics. The trial enrolled MM patients who had tried between 1 and 3 prior lines of therapy, had relapsed or progressive disease, and had had at least a partial response to at least 1 prior line of therapy.

Overall, the median PFS for the KRd group was 26.3 months, compared to 17.6 months in the Rd group.

In the high-risk cytogenetics group — those with genetic subtypes t(4;14) or t(14;16) or del(17p) in at least 60% of plasma cells — the median PFS was 23.1 in the KRd arm and 13.9 months in the Rd arm. Among standard-risk patients, the median PFS was 29.6 months in the KRd arm and 19.5 months in the Rd arm.

About 5-fold more patients, regardless of whether they were standard- or high-risk, achieved a CR or better on KRd compared to Rd, said Herve Avet-Loiseau, MD, lead investigator and presenter of the data.

“I think,” he said, “it is now a standard of care for these high-risk patients.”

References

 

1. Moreau P, Joshua D, Chng W-J, et al. Impact of Prior Treatment on Patients with Relapsed Multiple Myeloma Treated with Carfilzomib and Dexamethasone Vs Bortezomib and Dexamethasone in a Subgroup Analysis of the Phase 3 Endeavor Study (NCT01568866)
2. Avet-Loiseau H, Fonseca R, Siegel D, et al. Efficacy and Safety of Carfilzomib, Lenalidomide, and Dexamethasone Vs Lenalidomide and Dexamethasone in Patients with Relapsed Multiple Myeloma Based on Cytogenetic Risk Status: Subgroup Analysis from the Phase 3 Study Aspire (NCT01080391). Presented at the 57th Annual Meeting of the American Society of Hematology. 2015 Dec 5-8. Orlando FL. Abstract 731.