On Location
In Multiple Myeloma, Carfilzomib Bests
Bortezomib, But Bortezomib Bests
Observation
Two multiple myeloma
(MM) studies – one in relapsed disease and the other
in newly diagnosed disease
after autologous stem cell
transplantation (ASCT) –
support the use of proteasome inhibitor therapy in
these settings.
The first, the phase III,
Meletios A. Dimopoulos, MD
open-label, multicenter ENDEAVOR study, compared
carfilzomib plus dexamethasone (Kd) with bortezomib plus dexamethasone (Vd) in 929 patients with
relapsed MM – all of whom had received up to three
prior treatments.1
While Kd is approved in the United States for
relapsed and refractory MM at 20/27 mg/m2 over
2-10 minutes, earlier-phase studies determined
that a dose of 20/56 mg/m2 over 30 minutes (the
maximum tolerated dose of Kd) led to higher response rates in this population, said study presenter
Meletios A. Dimopoulos, MD, from the University
of Athens in Greece during the American Society of
Clinical Oncology (ASCO) meeting.
Patients were randomized 1:1 to cycles of Kd
or Vd repeated until disease progression or unacceptable toxicity. Nearly one-fourth had high-risk
cytogenetic features.
After a median follow-up of 11.2 months, the
primary endpoint of progression-free survival (PFS)
was 18.7 months for Kd and 9.4 months for Vd
(p<0.0001), with twice as many patients achieving
a complete response (CR; 13% vs. 6%) or very good
partial response (VGPR; 54% vs. 29%).
While Kd had increased rates of grade ≥3 hypertension (9% vs. 3%), dyspnea (5% vs. 2.2%), and
cardiac failure (5% vs. 1.8%) than Vd, rates of grade
≥2 peripheral neuropathy were significantly lower
with Kd (6% vs. 32%; p<0.0001).
“Carfilzomib with dexamethasone was superior
to bortezomib with dexamethasone regardless of
age or prior bortezomib exposure,” Dr. Dimopoulos
concluded, noting that the drug combination could
represent a new standard of care for MM.
For patients with newly diagnosed MM following ASCT, however, bortezomib is an effective
consolidation therapy, according to an analysis of
two phase III trials comparing bortezomib with
observation conducted by Christian Straka, MD,
and colleagues, which was also presented at ASCO’s
annual meeting. The first trial (MMY3012) included
222 patients ≤60 years old, and the second trial
(MMY3013) included 158 patients 61-75 years old.2
Dr. Straka, from Schön Klinik Starnberger See in
Berg, Germany, noted that, while high-dose therapy
followed by ASCT remains the standard treatment
in this patient population, consolidation therapy is
an attractive treatment option that warrants further
investigation.
In both studies, patients (total N=371; median age
= 59 years) were randomized 1:1 to receive bortezomib (1.6 mg/m2 IV on days 1, 8, 15, 22 in four
35-day cycles) or observation only.
At the end of treatment, response rates (including
VGPR and higher, both before and after consolidation therapy) were greater for the 1