ECHELON-2: Brentuximab Vedotin Plus Chemotherapy in CD30-Positive Peripheral T-Cell Lymphoma
As reported by Horwitz et al in The Lancet, the phase III ECHELON-2 trial showed that brentuximab vedotin (Adcetris) plus cyclophosphamide, doxorubicin, and prednisone (CHP) improved progression-free and overall survival vs cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in previously untreated CD30-positive peripheral T-cell lymphomas. The trial supported the recent approval of brentuximab vedotin plus chemotherapy in this setting.
Data from ECHELON-2 were also presented at the 2018 American Society of Hematology (ASH) Annual Meeting & Exposition.
Study Details
In the double-blind trial, 452 patients from 132 sites in 17 countries with previously untreated CD30-positive peripheral T-cell lymphomas, targeting 75% with systemic anaplastic large cell lymphoma, were randomly assigned between January 2013 and November 2016 to receive brentuximab vedotin plus CHP (n = 226) or CHOP (n = 226) for six or eight 21-day cycles. All patients received cyclophosphamide 750 mg/m² and doxorubicin 50 mg/m² on day 1 of each cycle and oral prednisone 100 mg once daily on days 1 to 5 of each cycle, followed by either brentuximab vedotin 1.8 mg/kg and placebo or vincristine 1.4 mg/m² and placebo on day 1 of each cycle.
The primary endpoint was progression-free survival on blinded independent central review in the intent-to-treat population. Overall, 72% of the brentuximab vedotin group and 68% of the CHOP group had systemic anaplastic large cell lymphoma.
Progression-Free and Overall Survival
After median follow-up of 36.2 months, median progression-free survival was 48.2 months in the brentuximab vedotin group vs 20.8 months in the CHOP group (hazard ratio [HR] = 0.71, P = .0110). Three-year progression-free survival was 57.1% vs 44.4%. Hazard ratios were 0.29 (95% confidence interval [CI] = 0.11–0.79) among 98 patients with ALK-positive and 0.65 (95% CI = 0.44–0.95) among 218 patients with ALK-negative systemic anaplastic large cell lymphoma.
As of data cutoff, death had occurred in 23% of the brentuximab vedotin group vs 32% of the CHOP group (HR = 0.66, P = .0244). After median follow-up of 42.1 months, median overall survival was not reached in either group; 75th percentile overall survival was not reached in the brentuximab vedotin group vs 17.5 months in the CHOP group.
Adverse Events
Adverse events of grade ≥ 3 occurred in 66% of the brentuximab vedotin group vs 65% of the CHOP group. Diarrhea of any grade was more common in the brentuximab vedotin group (38% vs 20%). Serious adverse events occurred in 39% vs 38%. Adverse events led to discontinuation of treatment in 6% vs 7%. Febrile neutropenia occurred in 18% vs 15% and any grade peripheral neuropathy in 52% vs 55%. Adverse events led to death in 3% vs 4% of patients.
The investigators concluded, “Front-line treatment with [brentuximab vedotin plus] CHP is superior to CHOP for patients with CD30-positive peripheral T-cell lymphomas as shown by a significant improvement in progression-free survival and overall survival with a manageable safety profile.”
Steven Horwitz, MD, of Memorial Sloan Kettering Cancer Center, is the corresponding author for The Lancet article.
Disclosure: The study was funded by Seattle Genetics, Inc; Millennium Pharmaceuticals, Inc, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited; and the National Cancer Institute. The study authors’ full disclosures can be found at thelancet.com.
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