– Phase 3 international study presented at ASCO annual meeting –
Chicago, Ill., June 1, 2014 – 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) 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 secondary 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. R-CHOP included:
- 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 Millennium.
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.
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 website, http://www.millennium.com/.
Millennium: The Takeda Oncology Company
1Response was evaluated according to the 2007 Revised Response Criteria for Malignant Lymphoma