In a European phase II trial (BREACH) reported in the Journal of Clinical Oncology, Fornecker et al found that brentuximab vedotin (BV) plus doxorubicin, vinblastine, and dacarbazine (BV-AVD) improved the rate of positron-emission tomography (PET)-negative status after two cycles of treatment vs doxorubicin, bleomycin, vincristine, and dacarbazine (ABVD) in previously untreated patients with early-stage unfavorable-risk Hodgkin lymphoma.
A total of 170 patients aged ≤ 60 years with at least one unfavorable EORTC/LYSA criterion were randomly assigned 2:1 between March 2015 and October 2016 to four cycles of BV-AVD (n = 113) or ABVD (n = 57) followed by involved-node radiotherapy at 30 Gy. Treatment consisted of 28-day cycles of BV-AVD (BV at 1.2 mg/kg, doxorubicin at 25 mg/m2, vinblastine at 6 mg/m2, and dacarbazine at 375 mg/m2) once daily on days 1 and 15 and ABVD with bleomycin 10 mg/m2 and AVD at the same dose and schedule.
The primary endpoint was PET response after two cycles on independent review. The study was designed to test if the PET-negative rate after two cycles of BV-AVD was superior to 75%.
PET negativity after two cycles was observed in 93 (82.3%, 90% confidence interval [CI] = 75.3%–88.0%) of 113 patients in the BV-AVD group vs 43 (75.4%, 90% CI = 64.3%–84.5%) of 57 in the ABVD group.
At the end of treatment, investigator-assessed complete response was achieved in 98 patients (86.7%, 90% CI = 80.3%–91.6%) in the BV-AVD group vs 45 (78.9%, 90% CI = 68.1%–87.7%) in the ABVD group.
Progression-free survival at 2 years was 97.3% (95% CI = 91.9%–99.1%) vs 92.6% (95% CI = 81.4%–97.2%). A total of 33 patients (31%) in the BV-AVD group and 14 (29%) in the ABVD group had high total metabolic tumor volume (> 177 cm3); among these patients, progression-free survival at 2 years was 90.9% (95% CI = 74.4%–97.0%) vs 70.7% (95% CI = 39.4%–87.9%).
Grade 3 or 4 adverse events occurred in 86% of patients in the BV-AVD group and 69% of the ABVD group, most commonly hematologic events (neutropenia in 75% vs 62% and leukopenia in 35% vs 27%). Other grade 3 or 4 adverse events included febrile neutropenia in 8% vs 6%, infections in 8% vs 4%, gastrointestinal events in 12% vs 0%, and peripheral neuropathy in 3% vs 2%. Serious adverse events occurred in 26% vs 13% of patients. Some patients developed second primary malignancies: one patient in the BV-AVD group (renal cell carcinoma) and two in the ABVD group (renal cell carcinoma and basal cell carcinoma).
The investigators concluded, “BV-AVD demonstrated an improvement in the PET-negative rate compared with ABVD after two cycles.”
Luc-Matthieu Fornecker, MD, PhD, of the Department of Hematology, Institut de Cancérologie Strasbourg Europe (ICANS), is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was funded by Takeda Pharmaceuticals. For full disclosures of the study authors, visit ascopubs.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.