Long-Term OS Data Inform Brentuximab Vedotin Prescribing Info in Lymphoma

The FDA approved brentuximab vedotin plus chemotherapy for treating advanced Hodgkin lymphoma in March 2018. Supporting data for the approval came from the phase 3 ECHELON-1 trial.

United States prescribing information for brentuximab vedotin (Adcetris) plus chemotherapy in the treatment of patients with advanced Hodgkin lymphoma has been updated to include 6-year overall survival (OS) data from the phase 3 ECHELON-1 trial (NCT01712490), demonstrating the regimen’s benefit compared with chemotherapy alone, according to a press release from Seagen Inc.¹

In the ECHELON-1 trial, brentuximab vedotin plus doxorubicin (Adriamycin), vinblastine, and dacarbazine yielded a 6-year OS rate of 93.9% (95% CI, 91.6%-95.5%) compared with 89.4% (95% CI, 86.6%-91.7%) with doxorubicin plus bleomycin, vinblastine, and dacarbazine with a median follow-up of approximately 73 months. The experimental combination was found to decrease the risk of death by 41% vs standard chemotherapy (Hazard ratio [HR], 0.59; 95% CI, 0.396-0.879; P = .009).

Additionally, the 6-year progression-free survival (PFS) rates were 82.3% (95% CI, 79.1%-85.0%) vs 74.5% (95% CI, 70.8%-77.7%) in each respective arm.

Among those who had treatment-emergent peripheral neuropathy in the trial, 86% experienced resolution or improvement in the brentuximab vedotin arm compared with 87% in the chemotherapy arm. Moreover, 72% vs 79% of patients, respectively, achieved complete resolution, with 14% and 8% having improved peripheral neuropathy.

Additionally, the median time to complete resolution was 6.6 months, and the median time to partial improvement was 2.9 months. Of 28% of patients with ongoing neuropathy, 57% had grade 1 events, 30% had grade 2 events, 12% had grade 3 events, and less than 1% had grade 4 events.

Brentuximab vedotin produced no new safety signals in the ECHELON-1 trial.

“The ultimate goal in cancer research is to offer the best chance for a cure,” David Epstein, chief executive officer at Seagen, said in the press release. “Patients with advanced classical Hodgkin lymphoma are often young adults with their whole lives ahead of them. The [OS] data are a major step forward in cancer research, and the transformative benefit offered by the [brentuximab vedotin] regimen can profoundly impact the lives of these patients.”

In the phase 3 ECHELON-1 trial, investigators compared the efficacy of brentuximab vedotin plus chemotherapy vs chemotherapy alone among 1334 patients with previously untreated stage III or IV classic Hodgkin lymphoma.

Patients in the experimental arm received 1.2 mg/kg of brentuximab vedotin intravenously on days 1 and 15 of each 28-day cycle plus 25 mg/m² of doxorubicin intravenously, 6 mg/m² of vincristine intravenously, and 375 mg/m² of dacarbazine intravenously. Patients in the comparator arm received the same chemotherapy backbone plus 10 units/m² of bleomycin intravenously.

The primary end point was modified PFS based on independent review facility assessment. Secondary end points included OS, disease-free survival, overall response rate, and duration of response.

Patients 18 years and older with Ann Arbor stage III or IV Hodgkin lymphoma and an ECOG performance status of 0 to 2 were eligible for enrollment on the trial. Patients also needed to have bidimensional measurable disease documented through radiographic technique based on International Working Group Revised Criteria for Response Assessment for Malignant Lymphoma.

Those with nodular lymphocyte predominant Hodgkin lymphoma or cerebral/meningeal disease were not able to enroll on the trial. Patients were also unsuitable for enrollment if they had sensory or motor peripheral neuropathy or prior immunosuppressive chemotherapy, therapeutic radiation, or any immunotherapy within 12 weeks of beginning study treatment.

The FDA approved brentuximab vedotin plus chemotherapy for treating advanced Hodgkin lymphoma in March 2018.² Supporting data for the approval came from the ECHELON-1 trial.

References

1. Six-year overall survival results added to U.S. prescribing information for ADCETRIS® (brentuximab vedotin) as first-line treatment for advanced Hodgkin lymphoma. News release. June 14, 2023. Accessed June 19, 2023. bit.ly/3NdL9j6
2. FDA expands approval of Adcetris for first-line treatment of stage III or IV classical Hodgkin lymphoma in combination with chemotherapy. News release. FDA. March 20, 2018. Accessed June 19, 2023. bit.ly/3Jn5QIq