Study comparing subcutaneous, intravenous administration of VELCADE in relapsed MM patients presented at ASH

Dec 8 2010

Millennium: The Takeda Oncology Company today reported results from a randomized, international Phase III clinical trial comparing subcutaneous and intravenous administration of VELCADE^® (bortezomib) in patients with relapsed multiple myeloma (MM). These data were presented at the 52^nd annual meeting of the American Society of Hematology (ASH), held December 4-7 in Orlando, Florida.

“Subcutaneous administration upheld the established efficacy of VELCADE”

"The most important finding of this study was the dramatic reduction in peripheral neuropathy with subcutaneous administration of VELCADE, making it an attractive route of administration," said Philippe Moreau, M.D., University Hospital, Nantes, France.

The open-label, international, Phase III non-inferiority study was conducted in 222 patients with relapsed MM and compared the overall response rates (ORR) after 12 weeks of treatment with subcutaneous or intravenous VELCADE. The secondary endpoints of the study included ORR after 24 weeks, time to tumor progression (TTP), progression free survival (PFS), one-year overall survival (OS) and safety and tolerability of the two routes of administration. The results, which were presented by Professor Moreau, showed that the efficacy of subcutaneous and intravenous VELCADE was similar, and that subcutaneous VELCADE appeared to be associated with an improved safety profile over intravenous VELCADE.

"Subcutaneous administration upheld the established efficacy of VELCADE," said Nancy Simonian, M.D., Chief Medical Officer, Millennium. "Both routes of administration showed consistent results across all efficacy endpoints, including time to progression and overall survival."

A Phase 3 Prospective Randomized International Study (MMY-3021) Comparing Subcutaneous and Intravenous Administration of Bortezomib In Patients with Relapsed Multiple Myeloma (Abstract #312)

This Phase III trial examined 222 relapsed MM patients with a median age of 64.5. The results, which were presented by Professor Moreau showed:

• After 12 weeks of treatment with single-agent VELCADE ORR was 42 percent in both the subcutaneous and intravenous arms
• After an additional 12 weeks of treatment that included the addition of dexamethasone in patients who achieved a partial response or worse, ORR improved to 52 percent in both arms, including 22 and 20 percent CR/nCR in the intravenous and subcutaneous arms respectively
• In the subcutaneous arm, the median TTP was 10.4 months and the one-year OS rate was 72.6 percent compared with a median TPP of 9.4 months and a OS rate of 76.7 percent in the intravenous arm
• In the subcutaneous arm, 38 percent of patients experienced peripheral neuropathy of any grade, compared with 53 percent of patients in the intravenous arm>
• In the subcutaneous arm, 6 percent of patients experienced peripheral neuropathy of grade 3 or higher, compared with 16 percent in the intravenous arm>
• In the intravenous arm 70 percent of patients experienced adverse events of Grade 3 or higher; and 27 percent of patients discontinued therapy due to adverse events
• In the subcutaneous arm, 57 percent of patients experienced adverse events of Grade 3 or higher; and 22 percent of patients discontinued therapy due to adverse events

Patients were randomized 2:1 to receive subcutaneous or intravenous VELCADE 1.3 mg/m² on days 1, 4, 8 and 11 every 21 days for a total of 24 weeks. The study used vials containing 3.5 mg of VELCADE. Intravenous injections were administered at a dose of 1.3 mg/m² reconstituted in saline solution (3.5 mL) for a final concentration of 1 mg/mL as a 3- to 5-second IV push. Subcutaneous injections were administered at a dose of 1.3 mg/m² reconstituted in saline solution (1.4 mL) for a final concentration of 2.5 mg/mL. For the first 12 weeks, patients received VELCADE monotherapy. After 12 weeks, if a patient had no change or partial response (PR) as the best response and had not progressed, oral dexamethasone at 20 mg could be added on the day of and day after VELCADE dosing (days 1, 2, 4, 5, 8, 9 and 11, 12) in the last 12 weeks of therapy. At the end of 24 weeks, patients who had an unconfirmed partial response or who were evolving steadily to a delayed PR could receive 6 additional weeks of VELCADE. More than 35 percent of patients had received at least two prior therapies.