KEY TAKEAWAYS
- The HD21 phase 3 study analyzed the non-inferiority of BrECADD as compared to eBEACOPP in terms of PFS.
- The study randomized patients in a 1:1 ratio to either eBEACOPP or BrECADD, guided by PET2 and administered for 4-6 cycles.
- The 3-year PFS rates for eBEACOPP and BrECADD were 92.3% and 94.9%, respectively.
- The GHSG HD21 trial confirmed the non-inferiority of BrECADD compared to eBEACOPP.
In an international open-label phase III trial, researchers aimed to compare the non-inferiority of BrECADD to eBEACOPP with progression-free survival (PFS) as the primary endpoint. Adult patients aged ≤60 with Advanced Stage Classical Hodgkin Lymphoma (AS-cHL) were considered for the study. The patients were randomly assigned in a 1:1 ratio to receive PET2-guided 4–6 cycles of either eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) or BrECADD (BV, etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone). PET2 and PFS events were evaluated through a blinded panel review process.
The non-inferiority of the primary efficacy endpoint PFS was defined as an absolute difference which was less than 6% at the 5-year mark (HR <1.69). Researchers used the O’Brien-Fleming method with Lan-DeMets alpha-spending function and the actual information fraction to determine the significance level and HR bound for non-inferiority in the intention-to-treat (ITT) analysis set. About 100 PFS events were obtained, leading to an HR bound of 1.02 and a corresponding alpha level of 0.0108.
From July 2016 to August 2020, 1,500 patients were enrolled from 9 countries and 233 trial sites. The ITT population included 1,482 patients, with 740 patients receiving eBEACOPP and 742 patients receiving BrECADD. About 44% of participants were female, and the median age was 34 years, ranging from 18 to 61 years. Additionally, 47% of the group was considered high risk as per the international prognostic index greater than or equal to three. Baseline characteristics were well-balanced between treatment arms. Around 59% of patients received 4 cycles of therapy, while the remaining 41% received 6 cycles. The median follow-up was 40 months. The 3-year PFS rates for eBEACOPP and BrECADD were 92.3% and 94.9%, respectively. The corresponding point estimate for the HR was 0.63 (99% CI 0.37–1.07), which was below the pre-specified bound. A total of 37 patients (5%) in the eBEACOPP arm and 16 patients (2.2%) in the BrECADD arm experienced progression or early relapse of Hodgkin lymphoma (HL) within one year. The 3-year overall survival rates were 98.5% for both treatment groups.
The interim analysis of GHSG HD21 trial confirmed that BrECADD is not inferior to eBEACOPP. Moreover, researchers observed a significant decrease in early PFS events with BrECADD, which has led to a 3-year PFS rate of 94.9%. This suggests that individualized treatment with PET2-directed BrECADD is the most effective therapy for adult patients with AS-cHL.
Source: https://onlinelibrary.wiley.com/doi/10.1002/hon.3196_LBA5
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT02661503
Borchmann, P., Moccia, A. A., Greil, R., Schneider, G., Hertzberg, M., Schaub, V., Hüttmann, A., Keil, F., Dierlamm, J., Hänel, M., Novak, U., Meissner, J., Zimmermann, A., Mathas, S., Zijlstra, J. M., Fosså, A., Viardot, A., Hertenstein, B., Martin, S., Engert, A. BRECADD IS NON-INFERIOR TO EBEACOPP IN PATIENTS WITH ADVANCED STAGE CLASSICAL HODGKIN LYMPHOMA: EFFICACY RESULTS OF THE GHSG PHASE III HD21 TRIAL. Hematological Oncology, 41, 881-882. https://doi.org/10.1002/hon.3196_LBA5
