Horwitz S, et al. - In the ECHELON-2 trial, brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone (A+CHP) was compared to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) as treatment option for CD30-positive peripheral T-cell lymphomas, with a focus on the efficacy and safety. Given that encouraging activity and manageable safety profile have been reported in a phase 1 study. Findings demonstrated superiority of front-line treatment with A+CHP, compared with CHOP, for patients with CD30-positive peripheral T-cell lymphomas. A+CHP treatment resulted in a remarkable improvement in progression-free survival and overall survival and displayed a manageable safety profile.

Methods

• A double-blind, double-dummy, randomised, placebo-controlled, active-comparator phase 3 study, named ECHELON-2, was performed.
• Participants included eligible adults from 132 sites in 17 countries with previously untreated CD30-positive peripheral T-cell lymphomas (targeting 75% with systemic anaplastic large cell lymphoma).
• Stratified by histological subtype according to local pathology assessment and by international prognostic index score, randomization of participants (1:1) was done to receive either A+CHP or CHOP for six or eight 21-day cycles.
• In all patients, the administered treatment regimen comprised cyclophosphamide 750 mg/m² and doxorubicin 50 mg/m² on day 1 of each cycle intravenously and prednisone 100 mg once daily on days 1 to 5 of each cycle orally, followed by either brentuximab vedotin 1·8 mg/kg and a placebo form of vincristine intravenously (A+CHP group) or vincristine 1·4 mg/m² and a placebo form of brentuximab vedotin intravenously (CHOP group) on day 1 of each cycle.
• The primary endpoint, Using intent-to-treat, progression-free survival (primary endpoint) was analysed according to blinded independent central review.

Results

• Between Jan 24, 2013, and Nov 7, 2016, eligibility assessments were carried out in 601 patients, 452 patients were enrolled and 226 were randomly assigned to both the A+CHP group and the CHOP group.
• In the A+CHP group and in the CHOP group, the observed median progression-free survival was 48·2 months (95% CI 35·2–not evaluable) and 20·8 months (12·7–47·6), respectively (hazard ratio 0·71 [95% CI 0·54–0·93], p=0·0110).
• Between groups, similarity was observed in adverse events, including incidence and severity of febrile neutropenia (41 [18%] patients in the A+CHP group and 33 [15%] in the CHOP group) and peripheral neuropathy (117 [52%] in the A+CHP group and 124 [55%] in the CHOP group).
• In the A+CHP group and in the CHOP group, fatal adverse events were experienced by 7 (3%) patients and 9 (4%) patients, respectively.