|[June 01, 2014]
VELCADE® (bortezomib)-based Therapy Significantly Improved Progression-Free Survival Compared to Standard Therapy as Frontline Treatment of Patients with Mantle Cell Lymphoma in Phase 3 Study
CHICAGO --(Business Wire)--
Millennium: The Takeda Oncology Company today announced results from the
primary analysis of an international, randomized Phase 3 study that
showed treatment with a VELCADE® (bortezomib)-based
combination therapy demonstrated a 59 percent relative improvement in
the study's primary endpoint of progression-free survival (24.7 vs. 14.4
months; Hazard Ratio [HR] 0.63; P<0.001) among previously untreated
patients with mantle cell lymphoma (MCL (News - Alert)) compared to treatment with a
standard therapy. These data were presented today at the annual meeting
of the American Society of Clinical Oncology (ASCO).
After a median follow up of 40 months, median overall survival (OS), a
key secondary endpoint, had not been reached for patients who received
the VELCADE-based therapy (VELCADE, rituximab, cyclophosphamide,
doxorubicin, and prednisone [VcR-CAP]), while a median OS of 56.3 months
was observed in patients treated with the standard regimen (rituximab,
cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP]) (HR
0.80; P=0.173). Overall, among patients receiving VcR-CAP compared to
R-CHOP, serious adverse events (SAEs) were reported in 38 percent vs. 30
percent of patients, and grade =3 adverse events were reported in 93
percent vs. 85 percent of patients.
"This is one of the largest studies ever conducted in newly diagnosed
MCL. The substantial improvement seen in progression-free survival and
in secondary endpoints, including complete response, time to next
therapy and time to progression with the VELCADE-based regimen in newly
diagnosed mantle cell lymphoma patients, expands our understanding of
VELCADE's contribution to patients with MCL," said Franco Cavalli, MD,
Director of the Oncology Institute of Southern Switzerland.
"The 59 percent relative improvement in progression-free survival, along
with the trend suggesting improved OS with the VELCADE-based regimen,
has the potential to represent a significant advance in the frontline
treatment of mantle cell lymphoma for some patients," said Michael
Vasconcelles, MD, Global Head, Takeda Oncology Therapeutic Area Unit.
"Patients with relapsed MCL have benefited from access to VELCADE
therapy since 2006. We look forward to working with regulatory
authorities to bring this new information to physicians and patients in
the near future."
The open-label, multicenter, prospective study evaluated the efficacy
and safety of VcR-CAP vs. R-CHOP in 487 patients with newly diagnosed
Stage II, III or IV MCL who were ineligible or not considered for a bone
marrow transplant. An Independent Radiology Review Committee (IRC)
assessed the primary efficacy endpoint. Key secondary endpoints for
patients receiving VcR-CAP vs. R-CHOP included:
30.5 vs. 16.1 months median time to progression (HR 0.58; P<0.001)
44.5 vs. 24.8 months median time to subsequent anti-lymphoma treatment
(HR 0.50; P<0.001)
53 percent vs. 42 percent CR+CRu rate (P=0.007)1
The estimated four-year survival rate, which was not a pre-specified
endpoint, was 64.4 percent in the VELCADE-containing arm versus 53.9
percent in the control arm. Another seondary endpoint, the overall
response rate (complete response plus complete response with persistent
imaging abnormalities of unknown significance plus partial response;
i.e., CR+CRu+PR) was 92 percent in the VELCADE-containing arm compared
to 90 percent in the control arm (P=0.275).
VcR-CAP was associated with additional but manageable toxicity compared
to R-CHOP, consistent with the known side effects of VELCADE and the
R-CAP combination. Safety results for patients receiving VcR-CAP vs.
Similar rates of peripheral neuropathy between the VELCADE-containing
arm and the control arm in all-grade peripheral neuropathy, (30
percent vs. 29 percent); the rate of grade =3 peripheral neuropathy
was significantly higher in the VELCADE-containing arm (7.5 percent
vs. 4.1 percent)
72 percent vs. 19 percent rate of all-grade thrombocytopenia, but no
difference in bleeding events (6 percent vs. 5 percent)
88 percent vs. 74 percent rate of all-grade neutropenia; 60 percent
vs. 46 percent rate of infection
14 percent vs. 15 percent rate grade =3 febrile neutropenia
The abstract, titled "Randomized Phase 3 study of rituximab,
cyclophosphamide, doxorubicin, and prednisone plus vincristine (R-CHOP)
or bortezomib (VR-CAP) in newly diagnosed mantle cell lymphoma (MCL)
patients (pts) ineligible for bone marrow transplantation (BMT)
[Abstract #8500]," was presented by Franco Cavalli, MD, Oncology
Institute of Southern Switzerland.
VELCADE® (bortezomib) is co-developed by Millennium/Takeda
and Janssen Pharmaceutical Companies. Millennium is responsible for
commercialization of VELCADE in the U.S.; Janssen Pharmaceutical
Companies are responsible for commercialization in Europe and the rest
of the world. Takeda Pharmaceutical Company Limited and Janssen
Pharmaceutical K.K. co-promote VELCADE in Japan. VELCADE is approved in
the U.S. and 53 additional countries for the treatment of patients with
mantle cell lymphoma (MCL) who have received at least one prior
treatment. VELCADE is also approved in more than 90 countries for the
treatment of patients with multiple myeloma (MM) and has been used to
treat more than 550,000 patients worldwide.
The front line MCL open-label, multicenter study was conducted by
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
(J&JPRD), as part of J&JPRD's global co-development agreement with
VELCADE: Important Safety Information
VELCADE® (bortezomib) is approved for the treatment of
patients with multiple myeloma. VELCADE is also approved for the
treatment of patients with mantle cell lymphoma who have already
received at least one prior treatment.
Patients should not receive VELCADE if they are allergic to bortezomib,
boron or mannitol. VELCADE should not be administered intrathecally.
Women should avoid becoming pregnant or breastfeeding while taking
VELCADE. Patients with diabetes may require close monitoring and
adjustment of their medication.
VELCADE can cause serious side effects, including:
Peripheral neuropathy. Nerve problems, which can
be severe including muscle weakness, tingling, burning, pain, or loss
of feeling in the hands and feet.
Low blood pressure. A drop in blood pressure
resulting in dizziness, light headedness or fainting.
Heart problems. Heart rhythm problems and heart
failure including worsening of existing conditions. Symptoms may
include chest pressure or pain, palpitations, swelling of the ankles
or feet, or shortness of breath.
Lung problems, some of which have been fatal. Symptoms
include cough, shortness of breath, wheezing or difficulty breathing.
Liver problems. Liver failure including a yellow
discoloration of the eyes and skin.
Posterior reversible encephalopathy syndrome (PRES). A
rare, reversible condition involving the brain. Symptoms may include
seizures, high blood pressure, headaches, tiredness, confusion,
blindness, or other vision problems
Gastrointestinal problems. Nausea, vomiting, diarrhea
Thrombocytopenia and neutropenia. Lowering the
levels of blood cells, which could result in a higher risk for
infections or bleeding.
Tumor lysis syndrome (TLS). TLS is a
syndrome that causes a chemical imbalance in the blood that could lead
to heart and/or kidney problems.
Common side effects seen in patients receiving VELCADE include: fever,
decreased appetite, fatigue, rash.
These are not all of the possible side effects with VELCADE. Please see
the full Prescribing Information for VELCADE for a complete list
available at VELCADE.com.
About Millennium: The Takeda Oncology Company
Millennium: The Takeda Oncology Company, a leading biopharmaceutical
company based in Cambridge, Mass., markets a first-in-class proteasome
inhibitor and has a robust pipeline of oncology product candidates.
Additional information about Millennium is available through its
Editors' Note: This press release is also available under the Media
section of the Company's website at: www.millennium.com/InTheNews.aspx.
1 Response was evaluated according to the 2007 Revised
Response Criteria for Malignant Lymphoma
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