TY - JOUR
T1 - Overall Survival with Brentuximab Vedotin in Stage III or IV Hodgkin's Lymphoma
AU - Ansell, Stephen M
AU - Radford, John
AU - Connors, Joseph M
AU - Długosz-Danecka, Monika
AU - Kim, Won-Seog
AU - Gallamini, Andrea
AU - Ramchandren, Radhakrishnan
AU - Friedberg, Jonathan W
AU - Advani, Ranjana
AU - Evens, Andrew M
AU - Smolewski, Piotr
AU - Savage, Kerry J
AU - Bartlett, Nancy L
AU - Eom, Hyeon-Seok
AU - Abramson, Jeremy S
AU - Dong, Cassie
AU - Campana, Frank
AU - Fenton, Keenan
AU - Puhlmann, Markus
AU - Straus, David J
AU - ECHELON-1 Study Group
AU - Hutchings, Martin
N1 - Copyright © 2022 Massachusetts Medical Society.
PY - 2022/7/28
Y1 - 2022/7/28
N2 - BACKGROUND: Five-year follow-up in a trial involving patients with previously untreated stage III or IV classic Hodgkin's lymphoma showed long-term progression-free survival benefits with first-line therapy with brentuximab vedotin, a CD30-directed antibody-drug conjugate, plus doxorubicin, vinblastine, and dacarbazine (A+AVD), as compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). A planned interim analysis indicated a potential benefit with regard to overall survival; data from a median of 6 years of follow-up are now available.METHODS: We randomly assigned patients in a 1:1 ratio to receive up to six cycles of A+AVD or ABVD. The primary end point, modified progression-free survival, has been reported previously. The key secondary end point was overall survival in the intention-to-treat population. Safety was also assessed.RESULTS: A total of 664 patients were assigned to receive A+AVD and 670 to receive ABVD. At a median follow-up of 73.0 months, 39 patients in the A+AVD group and 64 in the ABVD group had died (hazard ratio, 0.59; 95% confidence interval [CI], 0.40 to 0.88; P = 0.009). The 6-year overall survival estimates were 93.9% (95% CI, 91.6 to 95.5) in the A+AVD group and 89.4% (95% CI, 86.6 to 91.7) in the ABVD group. Progression-free survival was longer with A+AVD than with ABVD (hazard ratio for disease progression or death, 0.68; 95% CI, 0.53 to 0.86). Fewer patients in the A+AVD group than in the ABVD group received subsequent therapy, including transplantation, and fewer second cancers were reported with A+AVD (in 23 vs. 32 patients). Primary prophylaxis with granulocyte colony-stimulating factor was recommended after an increased incidence of febrile neutropenia was observed with A+AVD. More patients had peripheral neuropathy with A+AVD than with ABVD, but most patients in the two groups had resolution or amelioration of the event by the last follow-up.CONCLUSIONS: Patients who received A+AVD for the treatment of stage III or IV Hodgkin's lymphoma had a survival advantage over those who received ABVD. (Funded by Takeda Development Center Americas and Seagen; ECHELON-1 ClinicalTrials.gov number, NCT01712490; EudraCT number, 2011-005450-60.).
AB - BACKGROUND: Five-year follow-up in a trial involving patients with previously untreated stage III or IV classic Hodgkin's lymphoma showed long-term progression-free survival benefits with first-line therapy with brentuximab vedotin, a CD30-directed antibody-drug conjugate, plus doxorubicin, vinblastine, and dacarbazine (A+AVD), as compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). A planned interim analysis indicated a potential benefit with regard to overall survival; data from a median of 6 years of follow-up are now available.METHODS: We randomly assigned patients in a 1:1 ratio to receive up to six cycles of A+AVD or ABVD. The primary end point, modified progression-free survival, has been reported previously. The key secondary end point was overall survival in the intention-to-treat population. Safety was also assessed.RESULTS: A total of 664 patients were assigned to receive A+AVD and 670 to receive ABVD. At a median follow-up of 73.0 months, 39 patients in the A+AVD group and 64 in the ABVD group had died (hazard ratio, 0.59; 95% confidence interval [CI], 0.40 to 0.88; P = 0.009). The 6-year overall survival estimates were 93.9% (95% CI, 91.6 to 95.5) in the A+AVD group and 89.4% (95% CI, 86.6 to 91.7) in the ABVD group. Progression-free survival was longer with A+AVD than with ABVD (hazard ratio for disease progression or death, 0.68; 95% CI, 0.53 to 0.86). Fewer patients in the A+AVD group than in the ABVD group received subsequent therapy, including transplantation, and fewer second cancers were reported with A+AVD (in 23 vs. 32 patients). Primary prophylaxis with granulocyte colony-stimulating factor was recommended after an increased incidence of febrile neutropenia was observed with A+AVD. More patients had peripheral neuropathy with A+AVD than with ABVD, but most patients in the two groups had resolution or amelioration of the event by the last follow-up.CONCLUSIONS: Patients who received A+AVD for the treatment of stage III or IV Hodgkin's lymphoma had a survival advantage over those who received ABVD. (Funded by Takeda Development Center Americas and Seagen; ECHELON-1 ClinicalTrials.gov number, NCT01712490; EudraCT number, 2011-005450-60.).
KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects
KW - Bleomycin/adverse effects
KW - Brentuximab Vedotin/adverse effects
KW - Dacarbazine/adverse effects
KW - Disease-Free Survival
KW - Doxorubicin/adverse effects
KW - Hodgkin Disease/drug therapy
KW - Humans
KW - Male
KW - Neoplasm Staging
KW - Testicular Neoplasms
KW - Treatment Outcome
KW - Vinblastine/adverse effects
UR - http://www.scopus.com/inward/record.url?scp=85135409813&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa2206125
DO - 10.1056/NEJMoa2206125
M3 - Journal article
C2 - 35830649
SN - 0028-4793
VL - 387
SP - 310
EP - 320
JO - The New England journal of medicine
JF - The New England journal of medicine
IS - 4
ER -