HL

Brentuximab vedotin plus AVD therapy shows improved modified PFS compared with ABVD in untreated stage III or IV HL

The management of advanced-stage Hodgkin’s lymphoma (HL) has improved over the past few decades as a result of modern onco-hematology. However, challenges remain such as balancing the advantage of early disease control against the disadvantage of late toxicity of the most commonly used first-line chemotherapy regimen; doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD).

A phase I dose-escalation study2 evaluating the use of frontline brentuximab vedotin (A) combined with either ABVD or doxorubicin, vinblastine, and dacarbazine (AVD) in patients with advanced Hodgkin’s lymphoma showed superior results for brentuximab plus AVD. Based on these findings, ECHELON-1, a large, international, open-label, randomized, multicenter, phase III study was conducted to compare A plus AVD with ABVD as frontline therapy in patients with stage III or IV classic Hodgkin’s lymphoma.

Results from the ECHELON-1 phase III study were presented during a plenary scientific session at the 59th Annual Meeting & Exposition of the American Society of Hematology (ASH) in Atlanta, GA, on December 10th, 2017. The talk was presented by Joseph M. Connors, MD, Division of Medical Oncology and Centre for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, Canada. This article is based on data presented at the live session and the publication in The New England Journal of Medicine.

 Highlights:
  • 1334 patients (median age = 36 years) were involved in the study that had either newly diagnosed advanced stage III (36%) or IV (64%) Hodgkin lymphoma (HL). They were randomly assigned in a 1:1 ratio to receive A+AVD (664 patients) or ABVD (670 patients)
  • The primary endpoint was modified progression-free survival (PFS) as determined by an independent review facility (IRF)
Efficacy
  • Independent review:
    • IRF-assessed 2-year modified PFS rate A+AVD vs ABVD: 82.1% (95% CI, 78.7–85.0) vs 2% (95% CI, 73.7–80.4)
    • Hazard Ratio (HR) for progression, death or modified progression: 0.77 (95% CI, 0.60–0.98), P = 0.03
  • Investigator review:
    • INV-assessed 2-year modified PFS rate A+AVD vs ABVD: 81.0% (95% CI, 77.6–83.9) vs4% (95% CI, 70.7–77.7)
    • HR for progression, death or modified progression: 0.73 (95% CI, 0.57–0.92), P = 0.007
  • 2-year Overall Survival (OS) for the A+AVD vs ABVD group: 96.6% (95% CI, 94.8–97.7) vs9% (95% CI, 92.2–96.4)
Safety
  • Most frequent adverse events (AEs) A+AVD vs ABVD:
    • Neutropenia 58% vs 45%
    • Febrile neutropenia 19% vs 8%

Doctor Connors concluded by stating that the results of the ECHELON-1 trial showed “significantly superior modified PFS with brentuximab vedotin in combination with AVD compared to standard treatment with ABVD. Moreover, A+AVD showed a manageable toxicity profile.” The presenter also added that these results are particularly important as A+AVD offers an effective treatment to older patients.

References
  1. Connors JM. et al. Brentuximab Vedotin Plus Doxorubicin, Vinblastine, Dacarbazine (A+AVD) As Frontline Therapy Demonstrates Superior Modified Progression-Free Survival Versus ABVD in Patients with Previously Untreated Stage III or IV Hodgkin Lymphoma (HL): The Phase 3 Echelon-1 Study. Plenary Scientific Session #6. ASH 59th Annual Meeting and Exposition, Atlanta, GA
  2. Younes A, Connors JMet al. Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed Hodgkin’s lymphoma: a phase 1, open-label, dose-escalation study. Lancet Oncology 2013;14:1348-1356
  3. Connors JM. et al. Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin’s Lymphoma. New England Journal of Medicine. 2017 Dec 10. DOI: 10.1056/NEJMoa1708984. [Epub ahead of print]