ECHELON-1
Trial question
What is the role of front-line chemotherapy with brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine in patients with previously untreated stage III or IV classical Hodgkin's lymphoma?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
42.0% female
58.0% male
N = 1334
1334 patients (558 female, 776 male)
Inclusion criteria: adult patients with previously untreated stage III or IV classical Hodgkin's lymphoma
Key exclusion criteria: nodular lymphocyte predominant Hodgkin's lymphoma; cerebral/meningeal disease; sensory or motor peripheral neuropathy; prior immunosuppressive chemotherapy, therapeutic radiation, or any immunotherapy within 12 weeks of first study drug dose
Interventions
N=664 brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (at a dose of 1.2 mg/kg, 25 mg/m², 6 mg/m², and 375 mg/m², respectively, IV on days 1 and 15 of each 28-day cycle for up to 6 cycles)
N=670 doxorubicin, bleomycin, vinblastine, and dacarbazine (at a dose of 25 mg/m², 10 U/m², 6 mg/m², and 375 mg/m², respectively, IV on days 1 and 15 of each 28-day cycle for up to 6 cycles)
Primary outcome
Progression-free survival at 5 years
82.2
75.3
82.2 %
61.7 %
41.1 %
20.6 %
0.0 %
Brentuximab vedotin, doxorubicin, vinblastine, and
dacarbazine
Doxorubicin, bleomycin, vinblastine, and
dacarbazine
Significant
increase ▲
NNT = 14
Significant increase in progression-free survival at 5 years (82.2% vs. 75.3%; HR 1.47, 95% CI 1.15 to 1.89)
Secondary outcomes
Significant increase in progression-free survival at 5 years, among patients with PET scan negativity rate at cycle 2 (84.9% vs. 78.9%; HR 1.51, 95% CI 1.13 to 2)
No significant difference in progression-free survival at 5 years, among patients with PET scan positivity rate at cycle 2 (60.6% vs. 45.9%; HR 1.42, 95% CI 0.79 to 2.56)
Safety outcomes
No significant difference in improvement or resolution of peripheral neuropathy.
Conclusion
In adult patients with previously untreated stage III or IV classical Hodgkin's lymphoma, brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine were superior to doxorubicin, bleomycin, vinblastine, and dacarbazine with respect to a progression-free survival at 5 years.
Reference
David J Straus, Monika Długosz-Danecka, Joseph M Connors et al. Brentuximab vedotin with chemotherapy for stage III or IV classical Hodgkin lymphoma (ECHELON-1): 5-year update of an international, open-label, randomised, phase 3 trial. Lancet Haematol. 2021 Jun;8(6):e410-e421.
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