New Orleans, LA, December 7, 2013 – Millennium: The Takeda Oncology Company with its parent company, Takeda Pharmaceutical Company Limited (TSE:4502), today announced results from a retrospective, subgroup analysis of the Phase 3 VISTA study that showed a higher cumulative dose of VELCADE® (bortezomib) suggests improved overall survival (OS) in previously untreated patients with multiple myeloma (MM) (hazard ratio [HR] 0.53; p<0.0001). Patients who received a cumulative dose of VELCADE of 39 mg/m2 or greater lived 20 months longer on average than those who received lower cumulative doses (median OS 66.3 months and 46.2 months, respectively). The subgroups were determined post-randomization and the analysis was retrospective.
The retrospective analysis was conducted using data from the VISTA study, which evaluated the safety and efficacy of a VELCADE-melphalan-prednisone (VMP) regimen of up to 54 weeks compared with melphalan-prednisone (MP) alone in patients with previously untreated MM. These data were presented today at the 55th American Society of Hematology (ASH) annual meeting held in New Orleans, LA on December 7-10, 2013.
"VISTA showed an overall survival benefit in multiple myeloma and it reinforces the importance of treating patients with a twelve-month course of VELCADE therapy,” said María-Victoria Mateos, MD, University Hospital of Salamanca, Salamanca, Spain. "This subgroup analysis, while retrospective, suggests that patients who received a dose of 39 mg/m2 or greater fared better than those who received a lesser dose."
VELCADE is approved by the U.S. Food & Drug Administration (FDA) for the treatment of MM and relapsed mantle cell lymphoma (MCL).
“Ten years after its introduction, VELCADE continues to make a difference in the lives of patients with multiple myeloma,” said Michael Vasconcelles, MD, Head, Oncology Therapeutic Area Unit, Takeda Pharmaceutical Company. “As we work to discover and bring new therapies to patients, we are also committed to helping patients get the most out of the treatments currently available.”
Higher Cumulative Bortezomib Dose Results in Better Overall Survival (OS) in Patients with Previously Untreated Multiple Myeloma Receiving Bortezomib-Melphalan-Prednisone (VMP) in the Phase 3 VISTA Study (Abstract #1968)
The poster presentation featured a retrospective, subgroup analysis of data from the VMP arm of the Phase 3 VISTA study that examined whether increased cumulative bortezomib dosing (total dosing received during the study) led to improved long-term outcomes. The VISTA study evaluated VMP vs. MP in transplant-ineligible patients with previously untreated MM in terms of response rates, time to progression (primary endpoint), and OS. The subgroups analyzed were determined post-randomization. The VMP subgroup analysis was presented by María-Victoria Mateos, MD, who reported the following:
- The median cumulative dose in the overall VISTA trial was 39 mg/m2. The median treatment durations were 2.5 months (range, 0.1 to 13.9) for patients receiving less than 39 mg/m2 and 12.1 months (range, 5.2 to 13.9) for patients receiving 39 mg/m2 or greater. Some patients could continue MP treatment after stopping VELCADE, so the maximum values are 13.9 for both.
- OS was longer in patients in the higher (≥39 mg/m2) vs. lower (<39 mg/m2) cumulative dose group (median 66.3 vs. 46.2 months; HR 0.53; p<0.0001).
- The HR for OS between the two groups, adjusted for age differences, that were significant between the two groups, was 0.56 (p=0.0002).
- A landmark analysis showed that in patients who survived past the 180-day threshold, OS was longer in the higher (≥39 mg/m2) vs. lower (<39 mg/m2) cumulative dose group (median 60.4 vs. 50.3 months; HR 0.71; p=0.04).
- Primary reasons for discontinuation of therapy included adverse events (27 percent vs. 4 percent with <39 mg/m2 vs. ≥39 mg/m2), patient choice (17 percent vs. 2 percent), disease progression (9 percent vs. 5 percent), mortality (8 percent vs. 1 percent) and other reasons (8 percent vs. 4 percent).
As with all retrospective analyses, these data do not warrant the same merit as a prospective randomized trial.
Patients (n=340) treated with the VMP regimen in VISTA received up to nine six-week cycles (up to 54 weeks) of the combination therapy (cycles 1-4: VELCADE 1.3 mg/m2 IV, days 1, 4, 8, 11, 22, 25, 29, 32; cycles 5-9: VELCADE 1.3 mg/m2 IV, days 1, 8, 22, 29; all cycles: melphalan 9 mg/m2 and prednisone 60 mg/m2). The maximum planned dose of VELCADE was 67.6 mg/m2, including 41.6 mg/m2 during cycles 1-4 and 26 mg/m2 during cycles 5-9. The median cumulative VELCADE dose received was 39 mg/m2, which was selected as the cut-off point for defining patient groups by cumulative VELCADE dose for analyses of OS. A landmark analysis of OS from 180 days after the first dose to approximately align with cycles 1-4 of the study was conducted.
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 more than 90 countries and has been used to treat more than 450,000 patients worldwide.
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 and constipation.
- Thrombocytopenia and neutropenia. Lowering the levels of blood cells, which could result in a higher risk for infections or bleeding.
- Tumor lysis syndrome (TLS). TLSis 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.
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Located in Osaka, Japan, Takeda is a research-based global company with its main focus on pharmaceuticals. As the largest pharmaceutical company in Japan and one of the global leaders of the industry, Takeda is committed to strive towards better health for patients worldwide through leading innovation in medicine. Additional information about Takeda is available through its corporate website, www.takeda.com.
Editors’ Note: This press release is also available under the Media section of the Company’s website at: www.millennium.com/InTheNews.aspx.
Takeda Pharmaceutical Company Limited
Corporate Communications Dept. (PR/IR)