Data from Pharmawand - Curated by EPG Health - Date added 10 January 2019
Seattle Genetics, Inc.announced the publication of data from the ECHELON-1 phase III clinical trial online in the journal Clinical Cancer Research . The publication, titled “Brentuximab Vedotin Plus Chemotherapy in North American Patients with Newly Diagnosed Stage III or IV Hodgkin Lymphoma,” reports data from the North American patient population from ECHELON-1 evaluating Adcetris (brentuximab vedotin) in combination with AVD (Adriamycin,vinblastine and dacarbazine) in newly diagnosed stage III or IV classical Hodgkin lymphoma (HL). These data were previously presented in a poster presentation at the 2018 American Society of Clinical Oncology ( ASCO ) Annual Meeting.
In March 2018 , the FDA approved Adcetris in combination with AVD for the treatment of adult patients with previously untreated stage III or IV classical HL based on the positive results of the ECHELON-1 phase III clinical trial. Adcetris is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL that plays a role in tumor growth and survival.
“Prior to the FDA approval of Adcetris in combination with AVD, up to 30 percent of patients with advanced stage HL would not respond or would relapse following frontline treatment with ABVD (Adriamycin, bleomycin, vinblastine and dacarbazine),” said Clay Siegall , Ph.D., President and Chief Executive Officer of Seattle Genetics . “In this pre-specified analysis of 497 patients with HL treated in North America , similar to overall trial results, Adcetris plus AVD was associated with a lower risk of a progression event compared to ABVD. This is important information for North American healthcare providers to have when making treatment decisions, where there is access to supportive care, and treatment patterns and physician familiarity with treating patients with Acetris.”
Of the 1,334 advanced stage classical HL patients who participated in the ECHELON-1 clinical trial, 497 patients were treated in North America , with 250 patients in the Adcetris plus AVD arm and 247 patients in the ABVD control arm. The manuscript presents the North American results which include: A pre-specified sensitivity analysis showed per Independent Review Facility (IRF) assessment, the two-year modified progression-free survival (PFS) rate for patients in the Adcetris plus AVD arm was 84.3 percent compared to 73.7 percent in the control arm (HR 0.596; 95% CI: 0.40, 0.90), which corresponds to a difference of 10.6 percent. On the Adcetris plus AVD arm, peripheral neuropathy events were observed in 80 percent of patients compared to 56 percent on the ABVD arm. In the Adcetris plus AVD arm, the majority of peripheral neuropathy events were Grade 1 or 2 (41 percent and 21 percent, respectively). Grade 3 events were reported in 17 percent of patients. In the ABVD arm, Grade 3 events were reported in less than one percent of patients. There were no Grade 4 events on either arm. Across both arms of the study, approximately 75 percent of the patients with peripheral neuropathy reported resolution or improvement at last follow-up. Febrile neutropenia during treatment was reported in 20 percent of patients in the Adcetris plus AVD arm compared with nine percent in the ABVD arm. In the Adcetris plus AVD arm, 14 percent (35 patients) received primary prophylactic G-CSF within five days of starting treatment and nine percent (three patients) reported febrile neutropenia. Pulmonary toxicity was reported in three percent of patients in the Adcetris plus AVD arm versus ten percent of patients in the ABVD arm. Grade greater than 3 events were reported in two percent versus six percent of patients, in the Adcetris plus AVD and ABVD arms, respectively.
Comment:The trial demonstrated that combination treatment with brentuximab vedotin resulted in a statistically significant improvement in modified progression-free survival versus the control arm. For patients treated with brentuximab vedotin +AVD, there was a 23% reduction in the occurrence of an event, defined as progression, death or need for subsequent anti-cancer therapy for patients not in a complete response, compared to those who were treated with ABVD.