Health Canada Approves Adcetris-Chemo for Advanced Classical Hodgkin’s Lymphoma

Health Canada has approved Seattle Genetics‘ submission requesting approval of Adcetris (brentuximab vedotin) in combination with standard chemotherapy as a frontline treatment for patients with advanced (stage IV) classical Hodgkin’s lymphoma.

This approval — which makes the regimen accessible to physicians and eligible patients in Canada — was based on positive results of the ECHELON-1 Phase 3 trial (NCT01712490), where Adcetris plus AVD chemotherapy (adriamycin, vinblastine, and dacarbazine) decreased the risk of disease worsening, death, or need for additional cancer treatments, compared with AVBD (AVD bleomycin), a standard therapy for Hodgkin’s lymphoma patients.

Another application is under priority review by Health Canada, for the approval of Adcetris plus CHP chemotherapy (cyclophosphamide, doxorubicin, and prednisone) for the initial treatment of patients with CD30-positive peripheral T-cell lymphomas (PTCL). This submission also follows favorable results from another Phase 3 trial, ECHELON-2 (NCT01777152), where the Acetris combo reduced death risk by 34%, outperforming the standard-of-care chemotherapy.

Health Canada’s approval of Adcetris-chemo for advanced Hodgkin’s lymphoma “represents the first major advance for patients in decades,” Kerry Savage, MD, medical oncologist at the BC Cancer Agency, professor at the University of British Columbia, and a researcher in both ECHELON trials, said in a press release. “Advanced-stage Hodgkin lymphoma tends to be more aggressive and difficult to treat.”

“This new Adcetris-containing regimen demonstrated superior efficacy when compared to the standard of care ABVD chemotherapy in the phase 3 ECHELON-1 … and represents a meaningful advance for this Hodgkin lymphoma patient population,” she said.

ECHELON-1 was an open-label trial (NCT01712490) that included 1,334 classical Hodgkin’s lymphoma patients with advanced (stage III or IV) disease who had not received any prior treatment. Participants were randomly assigned to Adcetris plus AVD or AVBD chemotherapy alone.

At the end of treatment, a similar proportion of patients in both groups had responded to treatment — 86% for the Adcetris combo versus 83% for chemotherapy only.

But after a median follow-up of two years, 82.1% of patients assigned to Adcetris combo were alive, with no signs of disease progression or requiring additional treatment, compared with 77.2% in the chemotherapy group. This corresponded to a 23% reduction in risk of disease progression, need for additional treatment, or death.

Of note, patients whose disease spread to other regions in the body (metastatic) particularly benefited from Adcetris regimen, which reduced their risk by 29%.

Adcetris, developed by Seattle Genetics and Takeda, is an antibody-drug conjugate that targets the CD30 protein, located at the surface of many lymphomas. The compound is stable in the bloodstream but upon binding and entry into CD30-positive cells, it releases a toxic compound that causes cells to die.

“Currently, up to 30% of newly diagnosed patients with advanced-stage Hodgkin lymphoma will experience disease progression after treatment with the current standard of care, representing a significant need for improved treatment options,” said Clay Siegall, PhD, Seattle Genetics president and CEO. “With this new indication for Adcetris, physicians and eligible patients in Canada have access to this important new regimen for treating Stage IV Hodgkin lymphoma.”

One year ago, the U.S. Food and Drug Administration (FDA) approved Adcetris-chemo combo as a first-line therapy for patients with advanced classical Hodgkin’s lymphoma, as Health Canada did just now. The European Commission did the same this February.

In November last year, the FDA also approved Adcetris combination with CHP chemotherapy as an initial treatment for CD30-expressing PTCL, including angioimmunoblastic T-cell lymphoma and systemic anaplastic large cell lymphoma.