San Diego, CA—Patients with multiple myeloma receiving bortezomib (Velcade) in the pivotal VISTA trial lived more than 1 year longer than those in the control group, according to the final, 5-year analysis of the study presented at the 2011American Society of Hematology annual meeting.
The benefit was seen acrossmultiple prespecified patient subgroups and wasmaintained after 5 years of followup, despite substantial use of novel agents as salvage therapies. Patients who received bortezomib as first-line treatment had longer overall survival (OS) than those who received bor - tezomib or other therapies in subsequent treatment lines during the 5-year follow-up. “The OS subanalyses in patients receiving subsequent therapy demonstrate the importance of providing optimal first-line treatment that incorporates bortezomib, rather than reserving bortezomib for salvage therapy and using conventional first-line treatment,” said Jesús F. San Miguel, MD, PhD, of the Hospital Clinico Universitario in Salamanca, Spain, who presented the findings. VISTA Details The VISTA trial included 655 previously untreated patients with multiple myeloma who were randomized to nine 6-week cycles of bortezomib-melphalan-prednisone (VMP) or to the melphalan-prednisone (MP) regimen (ie, control group). Patients were followed at least every 12 weeks for survival and subsequent therapy use, with a median follow-up of 60.1 months. Dr San Miguel’s presentation was based on the final OS analysis of the study, representing 95% of the initial cohort (ie, only 5% in each arm were lost to follow-up). Mortality Risk Reduced by 31% At 5 years, mortality risk was reduced by 31% with VMP, based on a median OS of 56.4 months with the bortezomib-containing regimen and 43.1 months with MP (P = .004), Dr San Miguel reported. The median time to next treatment was 27 months with VMP versus 19.2 with MP (P <.001), and the treatmentfree interval was 16.6 months versus 8.3 months (P <.001). The benefit of adding bortezomib was seen across virtually all subsets of patients, including a 29% reduction in mortality among patients aged 75 years and older; a 23% risk reduction among those with International Staging System stage III disease; and a 30% risk reduction among patients with creatinine clearance <60 mL/min. However, the small subgroup of patients with documented high-risk cytogenetics did not gain additional benefit from bortezomib therapy. For this group of 46 patients, median OS was 44.1 months with VMP compared with 50.6 months with MP, which was not a significant difference. There was no reported increase in second malignancies. Dr San Miguel also reported that bortezomib was not associated with an increased incidence of secondary primary malignancies— a topic of recent concern in myeloma treatment. Hematologic malignancies were observed in only 1% in each arm, whereas solid tumors were seen in 5% of the VMP arm and 3% of the MP arm. “The overall incidence rate in both arms was consistent with the background rate of all cancers in the general US population aged 65 to 74 years,” Dr San Miguel said, adding that based on this large final analysis he believes that bortezomib “is completely safe.”
