medwireNews: A treatment regimen incorporating the anti-CD30 antibody–drug conjugate brentuximab vedotin is more effective than standard therapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) when used as a frontline therapy in patients with advanced Hodgkin lymphoma, phase III trial data show.
The findings, published in The New England Journal of Medicine and presented this week at the 2017 American Society of Hematology Annual Meeting in Atlanta, Georgia, USA, show that brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) reduced the risk for disease progression, death, or noncomplete response and use of subsequent anticancer therapy by a significant 23% compared with ABVD.
The ECHELON-1 researchers who conducted the randomized, multicenter, open-label study describe this result as “clinically meaningful”.
At a median 24.9 months of follow-up, the independently adjudicated 2-year modified progression-free survival rates were 82.1% among the 664 patients with previously untreated stage III or IV classic Hodgkin lymphoma who received A+AVD, and 77.2% in the 670 who received ABVD, a difference that was statistically significant.
Overall survival at 2 years was also better with A+AVD than with ABVD, although not significantly so, at 96.6% versus 94.9%.
Further analyses showed that the benefits of A+AVD extended across the majority of prespecified subgroups, with men, patients from North America, those with involvement of more than one extranodal site, an International Prognostic Score indicating a high risk of treatment failure (scores of 4 to 7), or stage IV disease, and patients younger than 60 years of age benefitting most.
Joseph Connors (British Columbia Cancer Agency, Vancouver, Canada) and colleagues report that while both groups completed a similar number of treatments cycles (5.5–5.7), the rates of neutropenia (58 vs 45%), febrile neutropenia (19 vs 8%), and peripheral neuropathy (67 vs 43%) were higher in the A+AVD group than in the ABVD group.
However, they point out that, among the patients who received A+AVD, the rate of febrile neutropenia was lower among the 83 patients who received primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) than among those who did not (11 vs 21%), and peripheral neuropathy resolved or improved in 67% of cases.
Pulmonary toxicity of grade 3 or higher was reported in less than 1% of patients in the A+AVD and in 3% of those in the ABVD group.
The researchers note that seven of nine deaths that occurred during treatment in the A+AVD group were associated with neutropenia (six had not received G-CSF and one had pre-existing neutropenia), while 11 of 13 deaths in the ABVD group were associated with pulmonary-related toxicity.
Given that older patients are at high risk from bleomycin-associated pulmonary toxicity, “the results of the ECHELON-1 trial are particularly important considering the opportunity A+AVD provides to administer a treatment to older patients that is at least equivalent in its effectiveness to ABVD, and to do so safely,” Connors et al conclude.
In an accompanying editorial, Dan Longo (Brigham and Women’s Hospital, Boston, Massachusetts, USA) and Vincent DeVita, Jr (Yale Cancer Center, New Haven, Connecticut, USA) write: “Although it is too early to rule out unanticipated late side effects, it appears that the addition of brentuximab vedotin to AVD combination chemotherapy (supported with G-CSF to alleviate myelotoxicity) merits consideration as first-line treatment for advanced Hodgkin’s lymphoma.
“Although the follow-up time has been relatively short, A+AVD appears to be more effective than ABVD (and is unlikely to be less effective) and is associated with fewer, more treatable toxicities.”
By Laura Cowen
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