Micrograph showing HL
Brentuximab vedotin (Adcetris®) in combination with a 3-drug chemotherapy regimen has met its primary endpoint of statistically significant improvement in modified progression-free survival (mPFS) compared with standard therapy in frontline treatment of advanced stage Hodgkin lymphoma (HL).
The ECHELON-1 trial tested brentuximab vedotin plus Adriamycin, vinblastine, and dacarbazine (AVD) against Adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) in 1334 patients with previously untreated advanced HL.
Patients treated with brentuximab showed an 82% lower risk of disease progression compared with 77% in the ABVD arm.
Brentuximab vedotin is currently not approved as a frontline therapy for HL.
“Notably, this is the first clinical trial in frontline advanced Hodgkin lymphoma to show superior efficacy of a regimen that eliminates bleomycin,” said Clay Siegall, PhD, president and CEO of Seattle Genetics.
Dirk Huebner, MD, executive medical director of oncology at Takeda Pharmaceutical Company, said the results of the trial “have the potential to change the treatment approach of frontline advanced Hodgkin lymphoma.”
Seattle Genetics and Takeda are jointly developing brentuximab vedotin. Seattle Genetics has US and Canadian commercialization rights and Takeda has rights to commercialize it in the rest of the world.
Brentuximab vedotin is an antibody-drug conjugate (ADC) made up of an anti-CD30 monoclonal antibody attached by a linker to monomethyl auristatin E (MMAE). The linker system is stable in the bloodstream but releases MMAE when internalized into CD30-expressing tumor cells.
ECHELON-1
ECHELON-1 (NCT01712490) is a randomized, 2-arm, multicenter phase 3 trial comparing brentuximab vedotin plus AVD to ABVD as frontline therapy in treatment-naïve advanced HL.
The trial enrolled 1334 patients with histologically confirmed advanced HL.
The primary endpoint is mPFS by independent review facility.
The investigators, regulatory bodies, and trial sponsors defined mPFS as the time to progression, death, or receipt of additional anticancer therapy for patients who were not in complete response (CR) after completion of frontline therapy.
They chose mPFS instead of PFS because they say it provides a clearer picture of the efficacy of primary anticancer therapy by eliminating the confounding effects of additional anticancer therapy.
Secondary endpoints include overall survival (OS), CR, and safety.
The results demonstrated that combination treatment with brentuximab resulted in a statistically significant improvement in mPFS versus the control arm (hazard ratio=0.770; P=0.035).
Interim analysis of OS, the key secondary endpoint, also trended in favor of the brentuximab plus AVD arm.
The safety profile of the brentuximab combination was consistent with that of the single-agent components of the regimen.
Patients in the brentuximab arm experienced an increased incidence of febrile neutropenia and peripheral neuropathy compared to the ABVD arm.
Febrile neutropenia was reduced with the use of prophylactic growth factors.
Peripheral neuropathy was managed through dose modifications.
Patients treated with ABVD had an increased rate and severity of pulmonary toxicity.
The companies plan to submit an abstract for presentation at the American Society of Hematology annual meeting in December.
Brentuximab is currently approved by the US Food and Drug Administration (FDA) for the treatment of patients with classical HL who have received a prior stem cell transplant or 2 prior chemotherapy treatments.
Brentuximab is also approved to treat patient with anaplastic large cell lymphoma who have failed one prior treatment.
For more on brentuximab vedotin, see the full prescribing informtion.
