Results from a Phase 3 clinical trial show that adding Adcetris (brentuximab vedotin) to a chemotherapy regimen reduces the risk of disease progression, death, or use of additional anticancer therapies for patients with untreated advanced Hodgkin’s lymphoma.
The study, “Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin’s Lymphoma,” was conducted at 218 sites across 21 countries. It was recently published in The New England Journal of Medicine.
Adcetris is an antibody-drug conjugate. It couples an antibody that specifically targets the CD30 protein, which is highly expressed on Hodgkin’s lymphoma cells, to a cytotoxic therapy. This means that the treatment is only released when the antibody binds to cancer cells, an approach that prevents toxicity to healthy cells and increases concentrations of the therapy in the cancer environment, where it will be most effective. Adcetris has been approved for the treatment of Hodgkin’s lymphoma after failure of initial treatments.
The current clinical trial (NCI1712490), also referred to as the ECHELON-1 study, evaluated the effectiveness of Adcetris in previously untreated advanced-stage patients. Patients were randomly assigned to receive Adcetris plus standard chemotherapies doxorubicin, vinblastine, and dacarbazine (A+AVD) or the standard chemotherapy regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).
ABVD is still one of the most commonly used treatment regimens for Hodgkin’s lymphoma and hasn’t been modified since its original description in 1975. However, up to 30 percent of patients with advanced Hodgkin’s lymphoma fail to achieve a complete response to this therapy. Additionally, bleomycin is associated with unpredictable pulmonary toxicities.
Results from the ECHELON-1 study show that A+AVD is significantly more effective than ABVD. After a median follow-up of 24.6 months, 82.1 percent of patients receiving Adcetris were alive and progression-free and had not required subsequent therapy to treat their disease. In the chemotherapy arm, that figure was 77.2 percent.
Importantly, patients in the Adcetris group also experienced less pulmonary toxicity and reported no new adverse events. The removal of bleomycin from the chemotherapy regimen is likely the reason for this improvement.
However, these patients did experience more cases of febrile neutropenia and infections compared to the chemotherapy group. Some of these adverse events can be treated with additional therapies.
The results show that replacing bleomycin with Adcetris not only improved survival outcomes but also reduced severe toxicities.
The improved outcomes associated with Adcetris are encouraging and suggest that Adcetris in combination with chemotherapy may be useful in treating older patients, for whom toxicities are of greater concern.