Findings from an international, randomised phase III trial involving patients with previously untreated stage III or IV classic Hodgkin’s lymphoma showed that patients assigned to receive brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) had superior efficacy to those who received doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), with a 4.9 percentage-point lower combined risk of progression, death, or non-complete response and use of subsequent anticancer therapy at 2 years. The results were presented at Plenary Scientific Session of the 59th Annual Meeting of the American Society of Hematology (ASH) and simultaneously published in the NEJM on 10 December 2017.
Brentuximab vedotin is an anti-CD30 antibody–drug conjugate that has been approved for relapsed and refractory Hodgkin’s lymphoma. The researchers from the ECHELON-1 Study Group conducted an open-label, multicenter, randomised phase III trial among patients with previously untreated stage III or IV classic Hodgkin’s lymphoma, in which 664 were assigned to receive A+AVD and 670 were assigned to ABVD regimen. The study primary endpoint was modified progression-free survival (PFS, the time to progression, death, or non-complete response and use of subsequent anticancer therapy) as adjudicated by an independent review committee. The key secondary endpoint was overall survival (OS).
At a median follow-up of 24.9 months, 2-year modified PFS rates in the A+AVD group was 82.1% (95% confidence interval [CI], 78.7 to 85.0) and 77.2% (95% CI, 73.7 to 80.4) in ABVD group, giving a difference of 4.9 percentage points (hazard ratio for an event of progression, death, or modified progression, 0.77; 95% CI, 0.60 to 0.98; p = 0.03).
There were 28 deaths with A+AVD and 39 with ABVD (hazard ratio for interim OS, 0.72 [95% CI, 0.44 to 1.17]; p = 0.19).
All secondary efficacy endpoints trended in favour of A+AVD.
Neutropenia occurred in 58% of the patients receiving A+AVD and in 45% of those receiving ABVD; in the A+AVD group, the rate of febrile neutropenia was lower among the 83 patients who received primary prophylaxis with granulocyte colony-stimulating factor than among those who did not (11% vs. 21%).
Peripheral neuropathy occurred in 67% of patients in the A+AVD group and in 43% of patients in the ABVD group; 67% of patients in the A+AVD group who had peripheral neuropathy had resolution or improvement at the last follow-up visit.
Pulmonary toxicity of grade 3 or higher was reported in less than 1% of patients receiving A+AVD and in 3% of those receiving ABVD.
Among the deaths that occurred during treatment, 7 of 9 in the A+AVD group were associated with neutropenia and 11 of 13 in the ABVD group were associated with pulmonary-related toxicity.
The authors concluded that compared with standard ABVD, A+AVD as frontline therapy improves outcome for patients with advanced Hodgkin’s lymphoma including a 23% risk reduction in progression, death, or need for additional anticancer therapy. These results establish A+AVD as a new frontline option for patients with advanced-stage Hodgkin’s lymphoma.
The study was funded by Millennium Pharmaceuticals and Seattle Genetics.