Adcetris is Approved for the Frontline Treatment of stage III or IV Classical Hodgkin Lymphoma in Combination with Chemotherapy

On March 20, 2018, the FDA granted Seattle Genetics, Inc. approval to market Adcetris® (Brentuximab Vedotin), in combination with chemotherapy, for the frontline treatment of patients with classical Hodgkin lymphoma (cHL) [1]. The standard frontline regimen for patients with cHL is a four-drug chemotherapy regimen, ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine); however, up to 30% of patients are refractory to treatment or relapse after treatment [2]. Brentuximab vedotin (BV) is a CD30-targeted antibody-drug conjugate that selectively delivers a cytotoxic agent to cHL cells, thus reducing systemic toxicity and enhancing anti-neoplastic activity [2]. Brentuximab vedotin was previously approved as a salvage treatment and post-transplantation consolidation therapy for patients with cHL as well as for the second-line treatment of systemic and primary anaplastic large cell lymphoma and CD30­expressing mycosis fungoides [1].

The most recent approval was based on the results of an open-label, multicenter, randomized phase 3 trial, ECHELON-1, comparing brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) to standard ABVD therapy for the frontline treatment of patients with stage III or IV cHL (NCT01712490) [3]. A total of 664 patients received A+AVD while 670 patients received ABVD. Efficacy was based on a 2-year modified progression-free survival (the time to progression, death, or noncomplete response and use of subsequent anticancer therapy) rate which was 82.1% for A+AVD group and 77.2% for the ABVD group [3]. Overall, patients receiving A+AVD experienced a 23% reduction in the risk of failure of the primary chemotherapy treatment. Additionally, treatment with A+AVD reduced the incidence of pulmonary toxicity supporting its use in this indication.

–Zachary Moore, on behalf of the Medical Content Team

1. ADCETRIS® (brentuximab vedotin) for injection, for intravenous use Drugs@FDA: FDA Approved Drug Products March 20, 2018 [cited 2018 April 26]; Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125388s097lbl.pdf.
2. Connors, J.M., et al., Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin’s Lymphoma. N Engl J Med, 2018. 378(4): p. 331-344.
3. Phase 3 Frontline Therapy Trial in Patients With Advanced Classical Hodgkin Lymphoma. ClinicalTrials.gov August 1, 2017 [cited 2018 April 27]; Available from: https://clinicaltrials.gov/ct2/show/NCT01712490.