Patrice Carde1, Matthias Karrasch2, Catherine Fortpied2, Pauline Brice2, Hussein Khaled2, Olivier Casasnovas2, Denis Caillot2, Isabelle Gaillard2, Serge Bologna2, Christophe Ferme2, Pieternella Johanna Lugtenburg2, Frank Morschhauser2, Igor Aurer2, Bertrand Coiffier2, Ralph Meyer2, Matthew Seftel2, Max Wolf2, Bengt Glimelius2, Anna Sureda2, Nicolas Mounier2. 1. Patrice Carde and Christophe Ferme, Gustave Roussy Cancer Campus, Villejuif; Pauline Brice, Hopital St. Louis, Paris; Olivier Casasnovas and Denis Caillot, Centre Hospitalier Universitaire (CHU) de Dijon, Dijon; Isabelle Gaillard, CHU Henri Mondor, Creteil; Serge Bologna, Centre Hospitalier Regional Universitaire (CHR) de Nancy, Nancy; Frank Morschhauser, CHR de Lille, Lille; Bertrand Coiffier, CHU de Lyon, Lyon; Nicolas Mounier, Hopital de L'Archet, Nice, France; Matthias Karrasch and Catherine Fortpied, European Organisation for Research and Treatment of Cancer Headquarters, Brussels, Belgium; Hussein Khaled, National Cancer Institute, Cairo, Egypt; Pieternella Johanna Lugtenburg, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands; Igor Aurer, University Hospital Centre Zagreb, Zagreb, Croatia; Ralph Meyer, Juravinski Cancer Centre, Hamilton, Ontario; Matthew Seftel, Cancer Care Manitoba, Winnipeg, Manitoba, Canada; Max Wolf, Peter MacCallum Cancer Institute, East Melbourne, Victoria, Australia; Bengt Glimelius, Uppsala University, Uppsala, Sweden; and Anna Sureda, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. dr.pcarde@gmail.com. 2. Patrice Carde and Christophe Ferme, Gustave Roussy Cancer Campus, Villejuif; Pauline Brice, Hopital St. Louis, Paris; Olivier Casasnovas and Denis Caillot, Centre Hospitalier Universitaire (CHU) de Dijon, Dijon; Isabelle Gaillard, CHU Henri Mondor, Creteil; Serge Bologna, Centre Hospitalier Regional Universitaire (CHR) de Nancy, Nancy; Frank Morschhauser, CHR de Lille, Lille; Bertrand Coiffier, CHU de Lyon, Lyon; Nicolas Mounier, Hopital de L'Archet, Nice, France; Matthias Karrasch and Catherine Fortpied, European Organisation for Research and Treatment of Cancer Headquarters, Brussels, Belgium; Hussein Khaled, National Cancer Institute, Cairo, Egypt; Pieternella Johanna Lugtenburg, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands; Igor Aurer, University Hospital Centre Zagreb, Zagreb, Croatia; Ralph Meyer, Juravinski Cancer Centre, Hamilton, Ontario; Matthew Seftel, Cancer Care Manitoba, Winnipeg, Manitoba, Canada; Max Wolf, Peter MacCallum Cancer Institute, East Melbourne, Victoria, Australia; Bengt Glimelius, Uppsala University, Uppsala, Sweden; and Anna Sureda, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Abstract
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 (ABVD8) or escalated-dose BEACOPP (BEACOPPescalated) for four cycles followed by baseline BEACOPP (BEACOPPbaseline) for four cycles (BEACOPP4+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 ABVD8 (n = 275) or BEACOPP4+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-up was 3.6 years. CR/CRu was 82.5% in both arms. At 4 years, EFS was 63.7% for ABVD8 versus 69.3% for BEACOPP4+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, treatment crossovers in five and 10 patients, and secondary malignancies in eight and 10 patients in the ABVD8 and BEACOPP4+4 arms, respectively. CONCLUSION:ABVD8 and BEACOPP4+4 resulted in similar EFS and OS in patients with high-risk advanced-stage HL. Because BEACOPP4+4 did not demonstrate a favorable effectiveness or toxicity ratio compared with ABVD8, treatment burden, immediate and late toxicities, and associated costs must be considered before selecting one of these regimens on which to build future treatment strategies.
RCT Entities:
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 (ABVD8) or escalated-dose BEACOPP (BEACOPPescalated) for four cycles followed by baseline BEACOPP (BEACOPPbaseline) for four cycles (BEACOPP4+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 ABVD8 (n = 275) or BEACOPP4+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-up was 3.6 years. CR/CRu was 82.5% in both arms. At 4 years, EFS was 63.7% for ABVD8 versus 69.3% for BEACOPP4+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, treatment crossovers in five and 10 patients, and secondary malignancies in eight and 10 patients in the ABVD8 and BEACOPP4+4 arms, respectively. CONCLUSION:ABVD8 and BEACOPP4+4 resulted in similar EFS and OS in patients with high-risk advanced-stage HL. Because BEACOPP4+4 did not demonstrate a favorable effectiveness or toxicity ratio compared with ABVD8, treatment burden, immediate and late toxicities, and associated costs must be considered before selecting one of these regimens on which to build future treatment strategies.
Authors: D Ghez; C Fortpied; N Mounier; P Carde; A Perrot; H Khaled; S Amorim; S Ramadan; F L Bras; M Erlanson; C Herbaux; J-P Marolleau; E Nicolas-Virelezier; O Casasnovas; A Stamatoullas-Bastard; C Fermé Journal: Bone Marrow Transplant Date: 2016-11-28 Impact factor: 5.483
Authors: Joseph M Connors; Wojciech Jurczak; David J Straus; Stephen M Ansell; Won S Kim; Andrea Gallamini; Anas Younes; Sergey Alekseev; Árpád Illés; Marco Picardi; Ewa Lech-Maranda; Yasuhiro Oki; Tatyana Feldman; Piotr Smolewski; Kerry J Savage; Nancy L Bartlett; Jan Walewski; Robert Chen; Radhakrishnan Ramchandren; Pier L Zinzani; David Cunningham; Andras Rosta; Neil C Josephson; Eric Song; Jessica Sachs; Rachael Liu; Hina A Jolin; Dirk Huebner; John Radford Journal: N Engl J Med Date: 2017-12-10 Impact factor: 91.245
Authors: Joseph M Connors; Wendy Cozen; Christian Steidl; Antonino Carbone; Richard T Hoppe; Hans-Henning Flechtner; Nancy L Bartlett Journal: Nat Rev Dis Primers Date: 2020-07-23 Impact factor: 52.329
Authors: Scott F Huntington; Gottfried von Keudell; Amy J Davidoff; Cary P Gross; Sapna A Prasad Journal: J Clin Oncol Date: 2018-10-04 Impact factor: 44.544