As reported in The New England Journal of Medicine by Stephen M. Ansell, MD, PhD, and colleagues, an analysis at 6 years of follow-up in the phase III ECHELON-1 trial has shown significantly improved overall survival with brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) vs doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in patients with previously untreated stage III/IV classical Hodgkin lymphoma.
At 5-year follow-up, A+AVD was associated with a significant long-term progression-free survival benefit (hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.53–0.87). A planned interim analysis indicated a potential benefit in overall survival as well.
Stephen M. Ansell, MD, PhD
In the multicenter open-label trial, 1,134 patients were randomly assigned to up to six cycles of A+AVD (n = 664) or ABVD (n = 670). The primary endpoint, modified progression-free survival, has been reported previously. The key secondary endpoint was overall survival in the intention-to-treat population.
At a median follow-up of 73.0 months, 39 patients (5.9%) in the A+AVD group and 64 (9.6%) in the ABVD group had died (HR = 0.59, 95% CI = 0.40–0.88, P = .009). The 6-year overall survival estimates were 93.9% (95% CI = 91.6%–95.5%) vs 89.4% (95% CI = 86.6%–91.7%).
In overall survival stratification subgroup analyses, the benefit of A+AVD appeared to be greater among 497 patients from North America (HR = 0.33, 95% CI = 0.15–0.70) than among 669 from Europe (HR = 0.78, 95% CI = 0.47–1.32) and among 339 patients with four to seven International Prognostic Score risk factors (HR = 0.48, 95% CI = 0.26–0.88) and among 712 with two or three risk factors (HR = 0.62, 95% CI = 0.33–1.14) than among 283 with no risk factors or one risk factor (HR = 0.97, 95% CI =0.34–2.77). Hazard ratios were 0.48 (95% CI = 0.29–0.80) among 846 patients with stage IV disease and 0.86 (95% CI = 0.45–1.65) among 483 with stage III disease.
In an updated progression-free survival analysis at a median follow-up of 72.6 months, 6-year progression-free survival was 82.3% vs 74.5% ABVD (HR = 0.68, 95% CI = 0.53–0.86).
Subsequent therapy was received by 20.4% vs 23.8% of patients, including autologous transplantation in 6.6% vs 9.0% and allogeneic stem cell transplantation in 0.6% vs 1.8%. Brentuximab vedotin alone or in combination was the most common subsequent therapy in the ABVD group (10.5%). Immunotherapies, primarily nivolumab, were used in 2.7% vs 4.2% of patients; radiotherapy was used in 8.3% vs 8.8%.
Second cancers were reported in 3.5% vs 4.9% of patients.
The investigators concluded, “Patients who received A+AVD for the treatment of stage III or IV Hodgkin’s lymphoma had a survival advantage over those who received ABVD.”
Dr. Ansell, of the Division of Hematology, Mayo Clinic, Rochester, is the corresponding author for The New England Journal of Medicine article.
Disclosure: The study was funded by Takeda Development Center Americas and Seagen. For full disclosures of the study authors, visit nejm.org.
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