Steven Horwitz, MD
The addition of brentuximab vedotin (Adcetris) to chemotherapy led to a clinically meaningful improvement in progression-free and overall survival (OS) in patients with CD30-expressing peripheral T-cell lymphoma (PTCL), according to phase III results of the ECHELON-2 trial presented at the 2018 ASH Annual Meeting and published online at Lancet Oncology
Brentuximab vedotin plus CHP (cyclophosphamide, doxorubicin, and prednisone; A+CHP) led to a 29% reduction in the risk of disease progression (HR, 0.71; 95% CI, 0.54-0.93; P
= .011), a 34% reduction in the risk of death (HR, 0.66; 0.46-0.95; P
= .0244), and a 3-year progression-free survival (PFS) rate of 57.1% versus 44% with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), announced lead study author Steven M. Horwitz, MD, in a presentation during the meeting.
“ECHELON-2 is the first prospective trial in peripheral T-cell lymphoma to show an overall benefit over CHOP,” said Horwitz, a medical oncologist at Memorial Sloan Kettering Cancer Center. “A+CHP provided clinically meaningful improvement in PFS and overall survival versus CHOP, with a 29% reduction in the risk of a progression event, and a 34% reduction in the risk of death.”
The FDA approved brentuximab vedotin for use in combination with chemotherapy for the frontline treatment of patients with CD30-expressing PTCL based on the ECHELON-2 findings in November 2018.
Frontline standard of care for patients with PTCL has been CHOP or CHOP-like regimen with curative intent, Horwitz explained. ALK
-positive systemic ALCL (sALCL), however, has more favorable outcomes depending on age and International Prognostic Index (IPI) score. Overall, there is an unmet need for new therapies for these patients as there is a high risk for relapse or disease progression. Approximately 50% of patients with PTCL express CD30, and it is universally expressed in patients with sALCL.
Prior phase I results of brentuximab vedotin plus CHP in the frontline setting showed that at 5 years, 50% of patients remain in remission and the median overall survival (OS) is not reached. Those results also showed that the combination has a manageable safety profile.3
ECHELON-2 (NCT01777152) is an international, double-blind, double-dummy, placebo-controlled, active comparator, randomized, phase III trial of 452 patients conducted at 132 sites in 17 countries. Patients were randomized 1:1 to receive brentuximab vedotin at 1.8 mg/kg, cyclophosphamide at 750 mg/m2
, doxorubicin at 50 mg/m2
, and prednisone at 100 mg on days 1 to 5, every 3 weeks for 6 to 8 cycles or CHP plus vincristine at 1.4 mg/m2
. G-CSF was given as primary prophylaxis or radiation therapy (RT) and stem cell transplantation (SCT) consolidation per investigator discretion. All patients then underwent EOT/PET scan imaging.
The primary endpoint was PFS per blinded independent central review (BICR), with SCT or RT consolidation therapy not counting as events. Secondary endpoints included OS, PFS per BICR in patients with sALCL, complete response rate, objective response rate, and safety. Endpoints were type I error controlled.
To be eligible for enrollment, patients with PTCL were ≥18 years of age, had ≥10% CD30 expression on cells, and received no prior treatment. Patients were stratified by IPI score (0-1 vs 2-3 vs 4-5) and histologic subtype: sALCL (70%), PTCL-not otherwise specified (NOS; 16%), angioimmunoblastic T-cell lymphoma (AITL; 12%), adult T-cell leukemia lymphoma (ATLL; 1.5%) enteropathy-associated T-cell lymphoma (EATL; 0.5%), and hepatosplenic T-cell lymphoma (HTCL; 0%).
Baseline characteristics were similar between both arms; the median age was 58 years old. The percentage of patients receiving A+CHP with an IPI score of 0 or 1, 2 to 3, and 4 to 5 were 23%, 62%, and 15% compared with those who received CHP at 21%, 64%, and 15%, respectively. Approximately 80.5% of patients had stage III/IV disease.
As of the data cutoff on August 15, 2018, treatment was completed in 85% of A+CHP treated patients and 79% of those who received CHOP. Patients who discontinued treatment due to disease progression, adverse events (AEs), and other was 3%, 7%, and 4% in the A+CHP arm and 12%, 7%, and 3% in the CHOP arm, respectively. Twenty-seven percent of patients receiving A+CHP received consolidative therapy versus 19% of those who received CHOP.
Subsequent therapy for residual or progression disease was administered in 26% and 42% of patients on the A+CHP and CHOP arms, respectively. Palliative radiation was given in 4% of patients in each group.