The results from the phase III APEX study have been published in The New England Journal of Medicine.
The study showed Velcade ( Bortezomib ) was superior in survival, time to disease progression, and response rates compared to standard of care, high-dose Dexamethasone, in patients with relapsed multiple myeloma.
The APEX study was halted at interim analysis in December 2003 at the recommendation of an independent Data Monitoring Committee due to significant prolongation of time to disease progression and significantly improved overall survival.
Based on these study findings, the FDA ( Food and Drug Administration ) approved a supplemental New Drug Application ( NDA ) in March 2005 for Velcade use in patients with multiple myeloma who have received at least one prior therapy.
To date, more than 24,000 patients have been treated with Velcade in more than 50 countries.
The APEX trial was conducted at 93 centers in North American, Europe and Israel and enrolled 669 patients with multiple myeloma who had received one to three prior therapies and randomized them to either treatment with single agent Velcade or high-dose Dexamethasone.
Results from 627 evaluable patients ( 315 treated with Velcade and 312 treated with Dexamethasone ) after a median 8.3 months follow- up included:
- Statistically significant survival advantage for patients treated in the single agent Velcade arm which was maintained even though 44 percent of patients crossed over to receive Velcade after experiencing progressive disease on the Dexamethasone arm;
- One-year survival rate with Velcade was 80 percent compared to 66 percent with Dexamethasone;
- Complete plus partial response rate with Velcade was 38 percent compared to 18 percent with Dexamethasone;
- Statistically significant higher complete and near complete responses ( 13 versus two percent ) were also found with Velcade;
- Median time to progression was improved by 78 percent ( 6.2 months on Velcade versus 3.5 months for Dexamethasone ).
" The study results highlight the advantage of Velcade in extending the survival of relapsed multiple myeloma patients," said Paul Richardson, Dana Farber Cancer Institute and author of the paper.
A prospective analysis was conducted in patients who had received only one prior therapy ( 38 percent of the overall patients in the study ) which also demonstrated significantly improved outcomes. Importantly, results showed that outcomes improved when Velcade was given to patients in earlier lines of therapy.
- Patients treated with Velcade versus Dexamethasone demonstrated statistically improved survival;
- Forty-five percent of patients achieved a complete or partial response with Velcade compared to 26 percent for Dexamethasone;
- Median time to progression was also significantly improved ( 7.0 months on Velcade versus 5.6 months for Dexamethasone ).
Adverse events reported in patients treated with Velcade were as previously reported and included gastrointestinal events, fatigue, neuropathy, pyrexia and hematologic toxicities.
Patients treated with Dexamethasone reported predictable adverse events including fatigue, insomnia, anemia and diarrhea.
The duration of treatment each patient received, rate of serious adverse events and rate of discontinuation due to an adverse event were similar in both treatment groups.
Source: The New England Journal of Medicine, 2005