Saulius Girnius, MD
Assistant Professor of Medicine
Division of Hematology-Oncology
University of Cincinnati
Cincinnati, OH
INTRODUCTION
Multiple myeloma is an incurable cancer of the plasma cells. The
American Cancer Society (ACS) estimates that in 2014, approximately 24,000 new cases of multiple myeloma will be diagnosed.1
The ACS also projects that approximately 11,000 deaths from multiple myeloma are expected to occur this year.
Treatment strategies aim to improve patients’ long-term
outcomes. As the treatment of multiple myeloma has advanced
in clinical practice, the evidence for how to treat patients with
VELCADE (bortezomib) has evolved. Over time, the body of evidence
for VELCADE has grown—redefining how VELCADE is used today.
THE VISTA TRIAL
Study Design
The VISTA trial was a randomized, open-label, international,
phase III trial that evaluated the efficacy and safety of intravenous
(IV) VELCADE in combination with melphalan + prednisone (MP)
vs MP alone in stem-cell transplant ineligible patients with previously untreated multiple myeloma (N = 682).
2, 3 Planned duration of
treatment was nine 6-week cycles (for a total of 54 weeks). After
progressive disease was established, all patients were eligible to
receive subsequent therapies.
4 The primary endpoint of the trial
was time to progression (TTP); secondary endpoints were complete
response (CR), objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).
2, 3
Study Results
At a prespecified interim analysis (median follow-up 16.3 months),
patients in the VELCADE + MP arm showed significantly supe-
rior results for TTP (median 20.7 months with VELCADE + MP vs
15.0 months with MP [P = .000002]), PFS, OS, and ORR.
3
Significantly superior response rates* were demonstrated in the
initial VISTA analysis (16.3-month median follow-up).
3 The ORR
was 69% with VELCADE + MP vs 34% with MP (P < 10-10).
3
Complete response (IF-) was 30% with VELCADE + MP vs 4%
with MP (P < 10-10).
3, 5
At this point in the study, further enrollment was halted, and patients receiving MP alone were offered the option to add VELCADE
to their regimen.
3 Updated analyses were performed subsequently.
3
At the 3-year median follow-up, VELCADE + MP provided an
OS advantage over MP that was not regained with subsequent
therapies.
3 Of the 69% of MP patients who received subsequent
therapies, 50% received VELCADE or a VELCADE-containing regimen.
4 Results in the VISTA trial were achieved with twice weekly IV
infusion for four 6-week cycles, followed by weekly VELCADE dosing for a median of 1 year (54 weeks planned).
4 At a 5-year median
follow-up, the median OS was 56.4 months with VELCADE + MP vs
43.1 months with MP alone (hazard ratio [HR], 0.695; 95% confidence interval [Cl], 0.57-0.85; P < .05) (Figure 1).
3
With Longer Duration of VELCADE,
Treatment Responses Deepened
Overall response rates through week 24 may be what some physicians see in clinical practice, but consider how many more patients
achieved their best response when treatment was continued beyond 24 weeks in the VISTA trial. In fact, 28% of CRs were achieved
after 24 weeks of therapy, although most had a response by
24 weeks. (Figure 2).
6
Safety
The most commonly reported adverse reactions (ARs) in the VISTA
trials for VELCADE + MP (n=340) vs MP alone (n=337) were thrombocytopenia (48% vs 42%), neutropenia (47% vs 42%), peripheral neuropathy (46% vs 1%), nausea (39% vs 21%), diarrhea
1 • AUGUST 2014 • FEDERAL PRACTITIONER SUPPLEMENT
Please see the accompanying full Prescribing Information for VELCADE on page 6.
A SUPPLEMENT TO
VOL. 31 SUPPL. 8
Treatment of Multiple Myeloma
with VELCADE® (bortezomib)
Dr. Girnius reports that he has no real or apparent conflicts of
interest in regards to this article.
This supplement is sponsored and co-developed
by Millennium Pharmaceuticals, Inc.
*Responses were based on criteria established by the European Group for
Blood and Marrow Transplant (EBMT).
3
