The ECHELON-2 Trial: 5-year results of a randomized, phase III study of brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma.

in Annals of oncology : official journal of the European Society for Medical Oncology by S Horwitz, O A O'Connor, B Pro, L Trümper, S Iyer, R Advani, N L Bartlett, J H Christensen, F Morschhauser, E Domingo-Domenech, G Rossi, W S Kim, T Feldman, T Menne, D Belada, Á Illés, K Tobinai, K Tsukasaki, S-P Yeh, A Shustov, A Hüttmann, K J Savage, S Yuen, P L Zinzani, H Miao, V Bunn, K Fenton, M Fanale, M Puhlmann, T Illidge

TLDR

  • The ECHELON-2 study compared two different treatments for a type of cancer called peripheral T-cell lymphoma (PTCL). The first treatment was called A+CHP, which included a drug called brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone. The second treatment was called CHOP, which included cyclophosphamide, doxorubicin, and prednisone. The study found that A+CHP provided better outcomes than CHOP in terms of progression-free survival (PFS) and overall survival (OS). The study also found that brentuximab vedotin retreatment after A+CHP provided an objective response rate of 59% in patients who relapsed, while the objective response rate after CHOP was 50%.

Abstract

For patients with peripheral T-cell lymphoma (PTCL), outcomes using frontline treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like therapy are typically poor. The ECHELON-2 study demonstrated that brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP) exhibited statistically superior progression-free survival (PFS) per independent central review and improvements in overall survival versus CHOP for the frontline treatment of patients with systemic anaplastic large cell lymphoma or other CD30-positive PTCL. ECHELON-2 is a double-blind, double-dummy, randomized, placebo-controlled, active-comparator phase III study. We present an exploratory update of the ECHELON-2 study, including an analysis of 5-year PFS per investigator in the intent-to-treat analysis group. A total of 452 patients were randomized (1 : 1) to six or eight cycles of A+CHP (N = 226) or CHOP (N = 226). At median follow-up of 47.6 months, 5-year PFS rates were 51.4% [95% confidence interval (CI): 42.8% to 59.4%] with A+CHP versus 43.0% (95% CI: 35.8% to 50.0%) with CHOP (hazard ratio = 0.70; 95% CI: 0.53-0.91), and 5-year overall survival (OS) rates were 70.1% (95% CI: 63.3% to 75.9%) with A+CHP versus 61.0% (95% CI: 54.0% to 67.3%) with CHOP (hazard ratio = 0.72; 95% CI: 0.53-0.99). Both PFS and OS were generally consistent across key subgroups. Peripheral neuropathy was resolved or improved in 72% (84/117) of patients in the A+CHP arm and 78% (97/124) in the CHOP arm. Among patients who relapsed and subsequently received brentuximab vedotin, the objective response rate was 59% with brentuximab vedotin retreatment after A+CHP and 50% with subsequent brentuximab vedotin after CHOP. In this 5-year update of ECHELON-2, frontline treatment of patients with PTCL with A+CHP continues to provide clinically meaningful improvement in PFS and OS versus CHOP, with a manageable safety profile, including continued resolution or improvement of peripheral neuropathy.

Overview

  • The ECHELON-2 study evaluated the efficacy of brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP) versus CHOP for the frontline treatment of patients with systemic anaplastic large cell lymphoma or other CD30-positive peripheral T-cell lymphoma (PTCL).
  • The study used a double-blind, double-dummy, randomized, placebo-controlled, active-comparator design with 452 patients randomized to six or eight cycles of A+CHP or CHOP. The primary objective was to assess the 5-year progression-free survival (PFS) and overall survival (OS) rates in the intent-to-treat analysis group. The study also analyzed the 5-year PFS and OS rates per investigator in the intent-to-treat analysis group. The study found that A+CHP provided clinically meaningful improvement in PFS and OS versus CHOP, with a manageable safety profile, including continued resolution or improvement of peripheral neuropathy. The study also found that brentuximab vedotin retreatment after A+CHP provided an objective response rate of 59% in patients who relapsed, while the objective response rate after CHOP was 50%.

Comparative Analysis & Findings

  • The ECHELON-2 study compared the outcomes observed under two different experimental conditions: A+CHP versus CHOP. The study found that A+CHP provided statistically superior progression-free survival (PFS) per independent central review and improvements in overall survival versus CHOP for the frontline treatment of patients with systemic anaplastic large cell lymphoma or other CD30-positive PTCL. The study also found that A+CHP provided clinically meaningful improvement in PFS and OS versus CHOP, with a manageable safety profile, including continued resolution or improvement of peripheral neuropathy. The study also found that brentuximab vedotin retreatment after A+CHP provided an objective response rate of 59% in patients who relapsed, while the objective response rate after CHOP was 50%.

Implications and Future Directions

  • The ECHELON-2 study's findings suggest that frontline treatment of patients with PTCL with A+CHP continues to provide clinically meaningful improvement in PFS and OS versus CHOP, with a manageable safety profile, including continued resolution or improvement of peripheral neuropathy. The study also highlights the potential of brentuximab vedotin retreatment after A+CHP as a viable option for patients who relapse. Future research should focus on further evaluating the long-term efficacy and safety of A+CHP and brentuximab vedotin retreatment in patients with PTCL, as well as exploring potential combinations with other therapies to improve outcomes. The study also highlights the importance of continued research on peripheral neuropathy management and prevention in patients receiving A+CHP and other chemotherapy regimens.
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