Brentuximab Vedotin Plus Doxorubicin, Vinblastine, and Dacarbazine Prolongs PFS in Hodgkin Lymphoma
Researchers randomly assigned 1334 patients with untreated stage III or IV HL to receive A + AVD or ABVD for 6 cycles.
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First-line therapy with brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A + AVD) improves progression-free survival (PFS) among patients with Hodgkin lymphoma (HL) compared with the long-time standard of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), according to an oral presentation at the 2017 American Society of Hematology (ASH) Annual Meeting in Atlanta, Georgia.1
For the open-label, phase 3 Echelon-1 study (ClinicalTrials.gov Identifier: NCT01712490), researchers randomly assigned 1334 patients with untreated stage III or IV HL to receive A + AVD or ABVD for 6 cycles.
Modified PFS outcomes were determined by both independent review facility (IRF; hazard ratio [HR], 0.770; 95% CI, 0.603-0.982; P = .035) and investigator (INV; HR, 0.725; 95% CI, 0.574-0.916; P = .007) assessment, with 146 events in the ABVD arm noted compared with 116 events in the A + AVD arm. The A + AVD and ABVD arms had 90 and 102 instances of disease progression, respectively, 18 and 22 deaths, and 9 and 22 cases of additional therapy being needed for an incomplete response.
Twenty-eight deaths were reported in the A + AVD arm compared with 39 deaths in the ABVD arm (HR, 0.721; 95% CI, 0.443-1.173; P = .186).
The safety profile of both regimens remained consistent with previous reports. A + AVD and ABVD had respective neutropenia rates of 58% and 45% (febrile neutropenia in 19% and 8%), peripheral neuropathy rates of 67% and 43%, pulmonary toxicity rates of 3% and less than 1%, and grade 3 or worse infection rates of 18% and 10%. Of the patients who had peripheral neuropathy in the A + AVD arm, 67% had resolution or improvement by the last follow-up.
Prophylaxis with a granulocyte colony-stimulating factor (G-CSF) reduced the rate of febrile neutropenia and grade 3 or worse infections and infestations. New patients assigned to A + AVD towards the end of the study were recommended G-CSF by the Independent Data Monitoring Committee to reduce the incidence of febrile neutropenia.
The authors concluded that this study “establishes A + AVD as a new frontline option for patients with advanced-stage HL.”
Read more of Cancer Therapy Advisor's coverage of the American Society of Hematology (ASH) 2017 meeting by visiting the conference page.
- Connors JM, Jurczak W, Straus DJ, et al. Brentuximab vedotin plus doxorubicin, vinblastine, dacarbazine (A+AVD) as frontline therapy demonstrates superior modified progression-free survival versus ABVD in patients with previously untreated stage III or IV Hodgkin Lymphoma (HL): the phase 3 Echelon-1 study. Oral presentation at: American Society of Hematology 59th Annual Meeting & Exposition; December 9-12, 2017; Atlanta, GA.