The European Commission has approved the used of Adcetris (brentuximab vedotin) in combination with standard chemotherapy for the initial treatment of advanced CD30-positive Hodgkin’s lymphoma patients in the European Union, Norway, Liechtenstein and Iceland.
The approval, which is for patients with locally advanced or metastatic disease, is based on positive data from the ECHELON-1 Phase 3 trial (NCT01712490), where the combination decreased the risk of disease worsening, death, or need for additional cancer treatments by 23%, compared with chemotherapy only.
For those whose disease has spread to other organs, this is the first new treatment in decades.
“The decision by the European Commission is a welcomed advancement for patients with previously untreated Stage IV [metastatic] Hodgkin lymphoma — a population that has not been offered a new treatment option in decades,” said Anna Sureda, MD, PhD, head of the Hematology Department and Hematopoietic Stem Cell Transplant Programme, Institut Català d’Oncologia — Hospital Duran i Reynals in Barcelona, Spain, said in a press release.
Adcetris, developed by Seattle Genetics and Takeda, is an antibody-drug conjugate that specifically targets the CD30 protein, widely produced by lymphoma cells. Once bound to CD30, Adcetris releases a toxic compound into cancer cells, causing their death.
ECHELON-1 was an open-label trial designed to compare the effects of standard chemotherapy — Adriamycin (doxorubicin), bleomycin, vinblastine, and dacarbazine (ABVD) — versus a combination of Adcetris and chemotherapy without bleomycin (AVD).
It included 1,334 classical Hodgkin’s lymphoma patients with advanced (stage 3 or 4) disease who had not received any prior treatment.
ECHELON-1’s main goal was to determine whether Adcetris could extend the time to disease worsening, death, or the need for a subsequent anti-cancer treatment. Secondary measures included overall survival, the number of patients responding to treatment or achieving full remission, adverse events, and duration of response.
At the end of treatment, a similar proportion of patients in both groups had responded to treatment – 86% for Adcetris versus 83% for chemotherapy only. Rates of complete responses were also similar – 73% versus 70%.
However, after a median follow-up of two years, 82.1% of patients on Adcetris were alive, without signs of disease progression or the need for additional treatment, compared to 77.2% in the chemotherapy arm. This represented a reduction in the risk of disease progression, need for additional treatment or death by 23%.
Patients with metastatic disease benefited even more from the combination, which reduced this risk by 29%.
A trend toward better survival rates was also observed in the Adcetris group, but few deaths have occurred to date (28 in the Adcetris arm and 39 in the chemotherapy group), and the results have not yet reached statistical significance.
Bleomycin is often associated with unpredictable pulmonary toxicities, and consistently, patients in the Adcetris arm — who did not receive bleomycin — exhibited less lung toxicity than those on standard chemotherapy. However, more patients on Adcetris experienced low neutrophil levels and peripheral neuropathy (damage to peripheral nerves).
“We are pleased that the European Commission has approved Adcetris in combination with AVD, which has the potential to represent an important milestone for patients and serves as a testament to Takeda’s longstanding commitment to the Hodgkin lymphoma community,” said Jesús Gómez-Navarro, MD, vice president, head of oncology clinical research and development for Takeda.
“The ECHELON-1 clinical trial demonstrated that the addition of Adcetris and the removal of bleomycin from the standard ABVD regimen yielded both efficacy and safety benefits in patients. We look forward to making this therapy available for appropriate European patients with Hodgkin lymphoma,” he said.