Brentuximab Vedotin Plus Doxorubicin, Vinblastine, and Dacarbazine Prolongs PFS in Hodgkin Lymphoma

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Researchers randomly assigned 1334 patients with untreated stage III or IV HL to receive A + AVD or ABVD for 6 cycles.
Researchers randomly assigned 1334 patients with untreated stage III or IV HL to receive A + AVD or ABVD for 6 cycles.
The following article features coverage from the American Society of Hematology (ASH) 2017 meeting. Click here to read more of Cancer Therapy Advisor's conference coverage.

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.

Reference

  1. 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.

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