Martin Hutchings1, John Radford2, Andrea Gallamini3, Arpad Illes4, Anna Sureda5, Joseph M. Connors6, Alice Sykorova7, Hirohiko Shibayama8, Jeremy S. Abramson9, Neil Chua10, Jonathan W. Friedberg11, Jan Koren12, Ann Steward LaCasce13, Lysiane Molina14, Neil Josephson15, Eric Song15, Hina Jolin16, Rachael Liu16, Ashish Gautam16, Stephen Ansell17
1Department of Haematology, Rigshospitalet, Copenhagen, Denmark,2University of Manchester and the Christie NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK,3Research, Innovation and statistics department, A Lacassagne Cancer Centre, Nice, France,4Department of Hematology, Faculty of Medicine, University of Debrecen, Hungary,5Clinical Hematology Department, Institut Català d‘Oncologia-Hospitalet, Barcelona, Spain,6British Columbia Cancer Agency Centre for Lymphoid Cancer, Vancouver, BC, Canada,7Charles University Hospital and Faculty of Medicine, Fourth Department of Internal Medicine – Haematology, Hradec Kralove, Czech Republic,8Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Japan,9Center for Lymphoma, Massachusetts General Hospital Cancer Center, Boston, MA, US,10Department of Oncology, Division of Medical Oncology, University of Alberta, Canada,11Wilmot Cancer Institute, University of Rochester, Rochester, NY, US,12Internal Clinic of Hematology, University Hospital, Vinohrady, Third Faculty of Medicine, Charles University in Prague, Prague, Czech Republic,13Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, US,14Service d‘hématologie clinique, CHU de Grenoble, Grenoble, France,15Seattle Genetics, Inc., Bothell, WA, US,16Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, US,17Mayo Clinic, Rochester, MN, US
Background: Primary results of the randomized, phase 3 ECHELON-1 study demonstrated a significant improvement in modified progression-free survival (mPFS), per independent review facility (IRF), in patients with stage III or IV cHL treated with frontline brentuximab vedotin + doxorubicin, vinblastine, and dacarbazine (A+AVD) vs doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD). Two-year mPFS rates were 82% and 77%, respectively. We report a prespecified subanalysis of the efficacy and safety of A+AVD vs ABVD in patients with cHL and high-risk features including: ≥1 extranodal site of involvement, stage IV disease, or an International Prognostic Score (IPS) of 4–7.
Methods: Patients were randomized 1:1 to receive up to six 28-day cycles of A+AVD or ABVD administered intravenously on days 1 and 15 of each cycle. Patients were analyzed by disease stage at diagnosis, IPS, and number of extranodal disease sites. Sub-group analyses were performed on the primary endpoint of mPFS (defined as time to progression, death, or evidence of noncomplete response followed by subsequent anticancer therapy).
Results: 664 and 670 patients were randomized to A+AVD and ABVD, respectively. High-risk features at baseline were well balanced in both treatment groups, with 64% and 63% having stage IV disease, and 25% and 27% having an IPS of 4–7 in A+AVD and ABVD arms, respectively; 62% of patients in each arm had ≥1 extranodal site. Two-year mPFS was most improved with A+AVD compared with ABVD in the following sub-groups (Table 1): stage IV disease (82.0% vs 75.3% [HR = 0.71, 95% CI: 0.53–0.96; p = 0.023]), >1 extranodal site (80.2% vs 71.1% [HR = 0.67, 95% CI: 0.44–1.00; p = 0.049], and ≥1 extranodal site (82.4% vs 74.9% [HR = 0.70, 95% CI: 0.52–0.94; p = 0.018]). Patients with an IPS of 4–7 also had a favorable improvement in mPFS with A+AVD (77.0% vs 69.2% [HR = 0.70, 95% CI: 0.46–1.07; p = 0.097]). Efficacy and safety analyses for combinations of high-risk sub-groups will be presented in full.
Conclusions: Compared with standard ABVD, frontline A+AVD trends favorably for mPFS outcomes for patients with high-risk cHL, suggesting that these patients might have a greater treatment benefit with A+AVD compared with ABVD.