The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the marketing authorization for brentuximab vedotin (BV).
The CHMP has recommended approval for BV (Adcetris) in combination with doxorubicin, vinblastine, and dacarbazine (AVD) to treat adults with previously untreated, CD30+, stage IV Hodgkin lymphoma (HL).
The CHMP’s recommendation will be reviewed by the European Commission (EC), which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.
The EC usually makes a decision within 67 days of a CHMP recommendation.
BV is already EC-approved to treat adults with:
- CD30+ HL at increased risk of relapse or progression following autologous stem cell transplant (ASCT)
- Relapsed or refractory, CD30+ HL following ASCT or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option
- Relapsed or refractory systemic anaplastic large-cell lymphoma
- CD30+ cutaneous T-cell lymphoma after at least one prior systemic therapy.
Phase 3 trial
The CHMP’s recommendation to approve BV in combination with AVD is supported by the phase 3 ECHELON-1 trial (NCT01712490).
In this trial, researchers compared BV plus AVD (BV+AVD) to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline treatment for 1334 patients with advanced HL.
The primary endpoint was modified progression-free survival (PFS), which was defined as time to progression, death, or evidence of non-complete response after completion of frontline therapy followed by subsequent anticancer therapy.
According to an independent review committee, BV+AVD provided a significant improvement in modified PFS compared to ABVD. The hazard ratio was 0.77 (P=0.035), which corresponds to a 23% reduction in the risk of progression, death, or the need for additional anticancer therapy.
The 2-year modified PFS rate was 82.1% in the BV+AVD arm and 77.2% in the ABVD arm.
There was no significant difference between the treatment arms when it came to response rates or overall survival.
The objective response rate was 86% in the BV+AVD arm and 83% in the ABVD arm (P=0.12). The complete response rate was 73% and 70%, respectively (P=0.22).
The interim 2-year overall survival rate was 97% in the BV+AVD arm and 95% in the ABVD arm (hazard ratio=0.72; P=0.19).
The overall incidence of adverse events (AEs) was 99% in the BV+AVD arm and 98% in the ABVD arm. The incidence of grade 3 or higher AEs was 83% and 66%, respectively, and the incidence of serious AEs was 43% and 27%, respectively.
Neutropenia, febrile neutropenia, and peripheral neuropathy were more common with BV+AVD, while pulmonary toxicity was more common with ABVD.
The ECHELON-1 trial was sponsored by Millennium Pharmaceuticals, Inc. (a Takeda company) in collaboration with Seattle Genetics, Inc.