Eight Cycles of ABVD Versus Four Cycles of BEACOPP(escalated) Plus Four Cycles of BEACOPP(baseline) in Stage III to IV, International Prognostic Score >= 3, High-Risk Hodgkin Lymphoma : First Results of the Phase III EORTC 20012 Intergroup Trial

Purpose To compare patients with high-risk stage III to IV Hodgkin lymphoma (HL) in the phase III European Organisation for Research and Treatment of Cancer 20012 Intergroup trial (Comparison of Two Combination Chemotherapy Regimens in Treating Patients With Stage III or Stage IV Hodgkin's Lymphoma) who were randomly assigned to either doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or to bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP). Patients and Methods Patients with clinical stage III or IV HL, International Prognostic Score of 3 or higher, and age 60 years or younger received ABVD for eight cycles (ABVD(8)) or escalated-dose BEACOPP (BEACOPP(escalated)) for four cycles followed by baseline BEACOPP (BEACOPP(baseline)) for four cycles (BEACOPP(4+4)) without radiotherapy. Primary end points were event-free survival (EFS), treatment discontinuation, no complete response (CR) or unconfirmed complete response (CRu) after eight cycles, progression, relapse, or death. Secondary end points were CR rate, overall survival (OS), quality of life, secondary malignancies, and disease-free survival in CR/CRu patients. Results Between 2002 and 2010, 549 patients were randomly assigned to ABVD(8) (n = 275) or BEACOPP(4+4) (n = 274). Other characteristics included median age, 35 years; male, 75%; stage IV, 74%; "B" symptoms, 81%; and International Prognostic Score >= 4, 59%. WHO performance status was 0 (34%), 1 (48%), or 2 (17%). Median follow-upwas 3.6 years. CR/CRu was 82.5% in both arms. At 4 years, EFS was 63.7% for ABVD(8) versus 69.3% for BEACOPP(4+4) (hazard ratio [HR], 0.86; 95% CI, 0.64 to 1.15; P = .312); disease-free survival was 85.8% versus 91.0% (HR, 0.59; 95% CI, 0.33 to 1.06; P = .076), and OS was 86.7% versus 90.3% (HR, 0.71; 95% CI, 0.42 to 1.21; P = .208). Death as a result of toxicity occurred in six and five patients, early discontinuation (before cycle 5) in 12 and 26 patients, treatme