According to research published in the Journal of Clinical Oncology, brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (BV-AVD) yielded an improvement in positron emission tomography (PET) response rate compared with standard doxorubicin, bleomycin, vincristine, and dacarbazine (ABVD) in previously untreated, early-stage unfavorable Hodgkin lymphoma.
In BREACH, a multicenter, open-label, randomized, phase 2 trial (ClinicalTrials.gov Identifier: NCT02292979), the researchers assessed the efficacy and safety of BV-AVD in adult patients, age 18-60 years, with previously untreated, early-stage unfavorable Hodgkin lymphoma (≥ 1 unfavorable EORTC/LYSA criterion).
Patients were randomly assigned (2:1) to receive 4 cycles of BV-AVD or ABVD followed by consolidation radiotherapy (30 Gy involved node). The primary endpoint was the PET response rate after 2 cycles according to an expert independent review (Deauville score).
The researchers designed the study to test if the PET-negative rate after 2 cycles of BV-AVD was superior to 75% and hypothesized there would be a 10% increase in the PET-negative rate after 2 cycles of BV-AVD relative to that of ABVD.
A total of 170 patients were enrolled between March 2015 and October 2016. Of these patients, 113 were assigned to the BV-AVD arm (median age, 29 years; range, 18-59), and 57 were assigned to the ABVD arm (median age, 28 years; range, 18-60). Baseline characteristics were well balanced between the arms.
Following 2 cycles of treatment, the primary end point was met, with 82.3% (90% confidence interval [CI], 75.3-88.0) the BV-AVD arm being PET-negative compared with 75.4% (90% CI, 64.3-84.5) of the ABVD arm.
The team also found that 2-year progression-free survival (PFS) was 97.3% (95% CI, 91.9-99.1) and 92.6% (95% CI, 81.4-97.2) in the BV-AVD and ABVD arms, respectively.
In a univariate analysis, 4 factors were associated with PFS: ECOG performance status 1-2 (hazard ratio [HR], 16.63; 95% CI, 2.1-135.2; P =.0006), total metabolic tumor volume (HR, 1.006; 95% CI, 1.0-1.0; P <.0001), total metabolic tumor volume >147 cm3 (HR, 17.89; 95% CI, 2.2-145.5; P <.001), and PET-negative after 2 cycles (HR, 0.18; 95% CI, 0.1-0.7; P =.02). The researchers could not perform multivariate analysis due to the small number of events.
The most frequently reported grade 3-4 adverse events were hematological toxicities (neutropenia, 75% with BV-AVD and 62% with ABVD; leukopenia, 35% and 27%, respectively; and febrile neutropenia, 8% and 6%, respectively). The team also reported grade 3-4 peripheral neuropathy in 3% the BVAVD arm and 2% of the ABVD arm.
Disclosure: This research was supported by Takeda Pharmaceuticals. Please see the original reference for a full list of disclosures.
Fornecker LM, Lazarovici J, Aurer I, et al. Brentuximab vedotin plus AVD for first-line treatment of early-stage unfavorable Hodgkin lymphoma (BREACH): a multicenter, open-label, randomized, phase II trial. J Clin Oncol. Published online July 22, 2022. doi:10.1200/JCO.21.01281