FDA Approves Bortezomib for Initial Treatment of Patients With Multiple Myeloma

The following is a message from the FDA's Office of Oncology Drug Products Director, Dr. Richard Pazdur:

On June 20, 2008, the U.S. Food and Drug Administration approved bortezomib for injection (Velcade^®, Millennium Pharmaceuticals, Inc., The Takeda Oncology Company, and Johnson and Johnson Pharmaceutical Research and Development) for the treatment of patients with multiple myeloma. This approval results from a clinical trial using Velcade as an initial treatment for patients with multiple myeloma. Velcade was previously approved in 2005 for the treatment of patients with multiple myeloma who had received at least one prior therapy and in 2003 for the treatment of more refractory multiple myeloma.

The current approval was based on an international, multicenter, open label, active-control trial in previously untreated patients with symptomatic multiple myeloma. Patients were randomized to receive either nine six-week cycles of oral melphalan (M) plus prednisone (P), or MP plus bortezomib. Patients received M (9 mg/m2) plus prednisone (60 mg/m2) daily for four days every six weeks or the same MP schedule with bortezomib, 1.3 mg/m2 iv on days 1, 4, 8, 11, 22, 25, 29, and 32 of every six-week cycle for four cycles then once weekly for four weeks on days 1, 8, 22, and 29 of every six-week cycle for five-additional cycles. Time-to-progression (TTP) was the primary efficacy endpoint. Overall survival (OS), progression-free survival (PFS), and response rate (RR) were secondary endpoints. The majority of the patients enrolled were ≥ 65 years of age. A total of 682 patients were randomized: 338 to receive MP and 344 to receive the combination of bortezomib plus MP. Demographics and baseline disease characteristics were similar between the two groups.

The trial was stopped following a pre-specified interim analysis showing a statistically significant improvement in TTP with the addition of bortezomib to MP (median 20.7 months) compared with MP (median 15 months) [HR: 0.54 (95 percent CI: 0.42, 0.70), p= 0.000002]. OS, PFS, and RR also were significantly superior for the bortezomib-MP combination.

The most common adverse reactions (incidence ≥30 percent) in clinical studies of bortezomib include asthenic conditions, diarrhea, nausea, constipation, peripheral neuropathy, vomiting, pyrexia, thrombocytopenia, psychiatric disorders, anorexia and decreased appetite, neutropenia, neuralgia, leukopenia, and anemia. Dose adjustment guidelines for hematologic and neurologic toxicity are detailed in the label (package insert).

Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions, and contraindications is available online.