FDA Approves Brentuximab Vedotin for Previously Untreated Stage III, IV Classical Hodgkin Lymphoma
On March 20, 2018, the U.S. Food and Drug Administration (FDA) approved brentuximab vedotin (Adcetris®) to treat adult patients with previously untreated stage III or IV classical Hodgkin lymphoma (cHL) in combination with chemotherapy.
Approval was based on a randomized, open-label, two-arm, multicenter trial, ECHELON-1, that randomized 1,334 patients to receive either brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (brentuximab vedotin + AVD) or bleomycin plus AVD (ABVD). Patients were randomized to receive up to 6 cycles of brentuximab vedotin + AVD or ABVD on days 1 and 15 of each 28-day cycle.
Efficacy was established based on modified progression-free survival (mPFS), defined as progression, death, or receipt of additional anticancer therapy for patients who are not in a complete response after completion of frontline therapy. The estimated median mPFS was not reached in either arm, with a median follow-up time of 24.6 months. There were 117 events (18%) on the brentuximab vedotin + AVD arm and 146 events (22%) on the ABVD arm (hazard ratio = 0.77; 95% CI = 0.60, 0.98; p = 0.035), corresponding to a 23% reduction in the risk of an mPFS event. At the time of the mPFS analysis, an interim overall survival analysis did not demonstrate a significant difference.
The most common adverse reactions in at least 20% of patients treated with brentuximab vedotin across all clinical trials were neutropenia, anemia, peripheral sensory neuropathy, nausea, fatigue, constipation, diarrhea, vomiting, and pyrexia. Primary G-CSF prophylaxis is recommended with brentuximab vedotin plus chemotherapy for the frontline treatment of stage III or IV cHL.
The recommended dose of brentuximab vedotin in combination with chemotherapy for previously untreated stage III or IV cHL is 1.2 mg/kg as an IV infusion up to a maximum of 120 mg every 2 weeks for 12 doses.
FDA granted this application priority review and breakthrough designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics (http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf).
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