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Brentuximab Vedotin (Adcetris) Wins Approval for Treatment of Hodgkin Lymphoma Patients
The FDA has given the green light to brentuximab vedotin (Adcetris, Seattle Genetics, Inc.) for the treatment of patients with classical Hodgkin lymphoma (HL) at high risk of relapse or progression as post-autologous hematopoietic stem-cell transplantation (auto-HSCT) consolidation.
The approval was based on results from the phase III AETHERA trial, which was designed to evaluate up to 16 cycles (approximately 1 year) of brentuximab therapy administered every 3 weeks after auto-HSCT in comparison with placebo. The study’s primary endpoint was met, with a significant improvement in median progression-free survival (PFS) of 42.9 months for patients who were treated with brentuximab compared with 24.1 months for patients who received placebo –– an improvement of 18.8 months (P = 0.001).
In addition, data from the AETHERA trial converted the FDA’s accelerated approval of the relapsed classical HL indication to regular approval.
Brentuximab vedotin is an antibody–drug conjugate directed to CD30, which is expressed in classical HL and in systemic anaplastic large-cell lymphoma (sALCL), as well as in other lymphoma subtypes.
This is the third indication for brentuximab, which was granted accelerated FDA approval in August 2011 for two other indications: 1) the treatment of Hodgkin lymphoma patients who fail autologous transplant or who fail at least two prior multi-agent chemotherapy regimens and are not autologous transplant candidates, and 2) the treatment of systemic ALCL patients who fail at least one prior multi-agent chemotherapy regimen. The sALCL indication is approved under accelerated approval based on the overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
The results from the AETHERA trial were published in The Lancet in March 2015. A total of 329 HL patients at risk of relapse or progression were enrolled, including 165 in the brentuximab arm and 164 in the placebo arm. The trial achieved its primary endpoint and demonstrated a significant increase in PFS per independent review facility, with a hazard ratio of 0.57 and a P value of 0.001. The median PFS was 43 months for patients treated with brentuximab compared with 24 months for patients who received placebo.
The most common adverse events, of any grade and regardless of causality, in the brentuximab arm included neutropenia (78%), peripheral sensory neuropathy (56%), thrombocytopenia (41%), anemia (27%), upper respiratory tract infection (26%), fatigue (24%), peripheral motor neuropathy (23%), nausea (22%), cough (21%), and diarrhea (20%).
Source: Seattle Genetics; August 17, 2015.