Brentuximab Vedotin plus Chemotherapy in North American Subjects with Newly Diagnosed Stage III or IV Hodgkin Lymphoma

• Published in: Clinical cancer research Vol. 25; no. 6; pp. 1718 - 1726
• Main Authors: Ramchandren, Radhakrishnan, Advani, Ranjana H., Ansell, Stephen M., Bartlett, Nancy L., Chen, Robert, Connors, Joseph M., Feldman, Tatyana, Forero-Torres, Andres, Friedberg, Jonathan W., Gopal, Ajay K., Gordon, Leo I., Kuruvilla, John, Savage, Kerry J., Younes, Anas, Engley, Gerald, Manley, Thomas J., Fenton, Keenan, Straus, David J.
• Format: Journal Article
• Language: English
• Published: United States 15.03.2019
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Bleomycin - administration & dosage; Bleomycin - adverse effects; Brentuximab Vedotin - administration & dosage; Brentuximab Vedotin - adverse effects; Canada; Chemotherapy-Induced Febrile Neutropenia - epidemiology; Chemotherapy-Induced Febrile Neutropenia - etiology; Dacarbazine - administration & dosage; Dacarbazine - adverse effects; Doxorubicin - administration & dosage; Doxorubicin - adverse effects; Female; Follow-Up Studies; Hodgkin Disease - drug therapy; Hodgkin Disease - mortality; Hodgkin Disease - pathology; Humans; Kaplan-Meier Estimate; Lung Injury - chemically induced; Lung Injury - epidemiology; Male; Middle Aged; Neoplasm Staging; Peripheral Nervous System Diseases - chemically induced; Peripheral Nervous System Diseases - epidemiology; Progression-Free Survival; United States; Vinblastine - administration & dosage; Vinblastine - adverse effects; Canada; United States
• DOI: 10.1158/1078-0432.CCR-18-2435
• ISSN: 1078-0432; 1557-3265

To evaluate safety and efficacy outcomes for subjects on the ECHELON-1 study treated in North America (NA). ECHELON-1 is a global, open-label, randomized phase III study comparing doxorubicin, vinblastine, and dacarbazine in combination with brentuximab vedotin (A+AVD) versus ABVD (AVD + bleomycin) as first-line therapy in subjects with stage III or IV classical Hodgkin lymphoma (cHL; NCT01712490). Subjects were randomized 1:1 to receive A+AVD or ABVD intravenously on days 1 and 15 of each 28-day cycle for up to 6 cycles. The NA subgroup consisted of 497 subjects in the A+AVD ( = 250) and ABVD ( = 247) arms. Similar to the primary analysis based on the intent-to-treat population, the primary endpoint [modified progression-free survival (PFS) per independent review] demonstrated an improvement among subjects who received A+AVD compared with ABVD (HR = 0.60; = 0.012). For PFS, the risk of progression or death was also reduced (HR = 0.50; = 0.002). Subsequent anticancer therapies were lower in the A+AVD arm. Grade 3 or 4 adverse events (AEs) were more common, but there were fewer study discontinuations due to AEs in the A+AVD arm as compared with ABVD. Noted differences between arms included higher rates of febrile neutropenia (20% vs. 9%) and peripheral neuropathy (80% vs. 56%), but lower rates of pulmonary toxicity (3% vs. 10%) in subjects treated with A+AVD versus ABVD. The efficacy benefit and manageable toxicity profile observed in the NA subgroup of ECHELON-1 support A+AVD as a frontline treatment option for patients with stage III or IV cHL.