Five-Year Results from the ECHELON-2 Trial Favor A+CHP Over CHOP in CD30-Positive PTCL

Meaningful improvement in progression-free survival (PFS) and overall survival (OS) was observed in patients with CD30-positive peripheral T-cell lymphoma (PTCL) who were treated with a regimen of brentuximab vedotin (Adcetris) plus cyclophosphamide (Cytoxan), doxorubicin (Adriamycin), and prednisone (A+CHP) vs cyclophosphamide, doxorubicin, vincristine (Oncovin), and prednisone (CHOP). Findings from the updated phase 3 trial were published in Annals of Oncology and included 5-year analysis of PFS and OS.¹

Investigators randomized 452 patients 1:1 to receive 6 or 8 cycles of A+CHP (n= 226) or cyclophosphamide, doxorubicin, vincristine (Oncovin), and prednisone (Deltasone; CHOP; n = 226). With a median follow up of 47.6 months, 5-year PFS rates were 51.4% (95% CI, 42.8%-59.4%) in the A+CHP arm versus 43.0% (95% CI, 35.8%-50.0%) in the CHOP arm (hazard ratio [HR] = 0.70; 95% CI, 0.53-0.91; P = .0077). Five-year OS rates were 70.1% (95% CI, 63.3%-75.9%) in patients treated with A+CHP versus 61.0% (95% CI, 54.0%-67.3%) in patients treated with CHOP (HR = 0.72; 95% CI, 0.53-0.99).

The ECHELON-2 trial (NCT01777152) is a double-blind, double-dummy, placebo-controlled, active-comparator phase 3 study. Investigators considered patients eligible if they were aged 18 years and over and had an ECOG performance status of no greater than 2 with previously untreated CD30-positive PTCL. The primary end point was PFS. Secondary end points included PFS in systemic anaplastic large cell lymphoma (sALCL), OS, complete remission (CR) rate, and objective response rate (ORR). Subsequent therapy was given after relapse.

Stage 3 disease presented in 27% of patients, and stage 4 disease presented in 53% of patients. Seventy percent of patients (n = 316) had sALCL.

The median PFS for the A+CHP arm was 62.3 months (95% CI, 42.0-not evaluable) compared with 23.8 months (95% CI, 13.6-60.8) for the CHOP arm. The estimated 5 year PFS for patients with sALCL was 60.6% (95% CI, 49.5%-69.9%) for A+CHP and 48.4% (95% CI, 39.6%-56.7%) for CHOP (HR = 0.55; 95% CI, 0.39-0.79; P = .0009). Median OS was not reached in both arms. The estimated 5-year OS rate was 70.1% (95% CI, 63.3%-75.9%) and 61.0% (95% CI, 54.0%-67.3%) for A+CHP and CHOP arms, respectively (HR = 0.72; 95% CI, 0.53-0.99, P = .0424).

Between both arms, patients received a median of 1 subsequent therapy per patient (range, 1-3). ORR for the first subsequent therapy was 42% in the A+CHP arm, with a 27% CR rate, and the ORR for the first subsequent therapy in the CHOP arm was also 42%, with a CR rate of 19%.

Twenty-nine patients in the A+CHP arm and 54 patients in the CHOP arm received systemic therapy with brentuximab vedotin after experiencing progressive disease or relapse after frontline therapy. Among these patients in the A+CHP arm, the ORR was 59%, 11 patients had CR, and 6 had partial remission (PR). Patients in the CHOP arm had an ORR of 50% with 16 having CR and 11 having PR.

Investigators found peripheral neuropathy (PN) in 117 patients in the A+CHP arm (52%) and in 124 patients in the CHOP arm (55%). Most PN events improved or resolved in 72% and 78% of the A+CHP and CHOP arms, respectively. The A+CHP arm experienced grade 1 PN in 33 (70%) of 47 patients, grade 2 for 13 (28%), and grade 3 for 1 (2%). The CHOP arm’s severity was grade 1 for 30 (64%) of 42 patients, grade 2 for 11 (23%), and grade 3 for 1 (2%).

_REFERENCE

_{Horwitz S, O'Connor OA, Pro B, et al. 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. Ann Oncol. 2022;33(3):288-298. doi:10.1016/j.annonc.2021.12.002}