Carfilzomib and dexamethasone versus eight cycles of bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma: an indirect comparison using data from the phase 3 ENDEAVOR and CASTOR trials

Abstract

In ENDEAVOR, carfilzomib and dexamethasone (Kd56) demonstrated significant improvement in progression-free survival (PFS) compared with bortezomib and dexamethasone (Vd). Both agents were administered until disease progression; the EU label for Vd, however, stipulates a maximum of eight treatment cycles. Here, matching-adjusted treatment comparison was used to compare efficacy of Kd56 with Vd, if Vd was administered for 8 cycles (Vd-8). Data from ENDEAVOR and CASTOR trials (which compared daratumumab, bortezomib, and dexamethasone with Vd-8) were used. Hazard ratios of PFS were estimated for Vd vs. Vd-8 and Kd vs. Vd-8. For cycles 1–8, risk reduction in PFS for Kd56 vs. Vd-8 was equal to that estimated in ENDEAVOR (HR: 0.53; 95% CI 0.44–0.65). Beyond eight cycles, risk reduction in PFS for Kd56 and Vd-8 was estimated to be 60% (HR: 0.40; 95% CI 0.26–0.63). The analysis suggested that PFS benefit of Kd56 over Vd increases when Vd is given for eight cycles only.

Keywords:

• Multiple myeloma
• proteasome inhibitor treatment duration
• matching-adjusted indirect treatment comparison

Disclosure statement

K. Weisel has participated in advisory boards for Amgen, BMS, Celgene, Janssen, Juno, Sanofi, and Takeda; has received honoraria from Amgen, BMS, Celgene, Janssen, Novartis, and Takeda; and has received research funding from Amgen, Celgene, Janssen, and Sanofi. I. M. Majer is an employee of Amgen (Europe) GmbH and holds Amgen stocks. L. DeCosta is an employee of Amgen Ltd and holds Amgen Stocks. A. Oriol has been a member of advisory boards for Amgen, Janssen, and Takeda. H. Goldschmidt has received research support from Amgen, BMS, Celgene, Chugai, Janssen, Mundipharma, Novartis, Sanofi, and Takeda; has participated in advisory boards for Adaptive Biotechnology, Amgen, BMS, Celgene, Janssen, Sanofi, and Takeda; and has received honoraria for speakers’ bureaux from ArtTempi, BMS, Celgene, Chugai, Janssen, and Novartis. H. Ludwig has received honoraria for speaker’s bureau from Amgen, BMS, Celgene, Janssen, and Takeda, as well as research grants from Amgen and Takeda. M. Campioni is an employee of Amgen (Europe) GmbH and holds Amgen stocks. Z. Szabo is an employee of Amgen (Europe) GmbH and holds Amgen stocks. M. Dimopoulos received consulting fees from Abbvie, Amgen, Celgene, Janssen, and Takeda.

Additional information

Funding

This analysis and the development of this manuscript were funded by Amgen (Europe) GmbH. Medical writing support, funded by Amgen (Europe) GmbH, was provided by Oxford PharmaGenesis, Oxford, UK. Editorial support was provided by Carine Thual of Amgen (Europe) GmbH.