title: R-CHOP with or without bevacizumab in patients with previously untreated diffuse large B-cell lymphoma: final MAIN study outcomes.
abstract: Vascular endothelial growth factor is involved in lymphoma growth, suggesting a potential role for anti-vascular endothelial growth factor therapies in hematologic malignancies. In this phase III study, patients with CD20-positive diffuse large B-cell lymphoma were randomized to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone plus either placebo (R-CHOP) or bevacizumab (RA-CHOP). Treatment was administered every 21 (8 cycles) or 14 days (6 cycles plus 2 rituximab cycles) as per institutional practice. An early analysis of risk/benefit by the Data and Safety Monitoring Board showed that RA-CHOP increased cardiotoxicity without prolonging progression-free survival compared with R-CHOP, and the trial was stopped early. The study protocol was amended to allow for 12 additional months of follow up to evaluate safety. With 787 patients enrolled, median follow up was 23.7 and 23.6 months for R-CHOP and RA-CHOP, respectively. Median progression-free survival for R-CHOP and RA CHOP was 42.9 and 40.2 months, respectively (hazard ratio=1.09; P=0.49). The proportion of deaths was identical for R-CHOP (83 of 387, 21%) and RA-CHOP (82 of 390, 21%). Relative to R-CHOP, RA-CHOP had a higher rate of left ventricular ejection fraction perturbation (18% vs. 8%; odds ratio=2.51; 95% confidence interval (CI): 1.60-3.93) and congestive heart failure (16% vs. 7%; odds ratio=2.79; 95%CI: 1.72-4.54). Bevacizumab added to R-CHOP increased cardiac events, without increasing efficacy, arguing against further evaluation of RA-CHOP in patients with diffuse large B-cell lymphoma. The MAIN study is registered at clinicaltrials.gov identifier:00486759.
authors.affiliation: Peter MacCallum Cancer Centre, East Melbourne, Australia University of Melbourne, Parkville, Australia John.Seymour@petermac.org.
authors.forename: John F
authors.initials: JF
authors.lastname: Seymour
authors.affiliation: Saarland University Hospital, Homburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Pfreundschuh
authors.affiliation: General Hospital, Charles University First Faculty of Medicine, Prague, Czech Republic.
authors.forename: Marek
authors.initials: M
authors.lastname: Trnĕný
authors.affiliation: Centre for Lymphoid Cancer, British Columbia Cancer Agency, Canada.
authors.forename: Laurie H
authors.initials: LH
authors.lastname: Sehn
authors.affiliation: Frankston Hospital and Monash University, Frankston, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Catalano
authors.affiliation: F. Hoffmann-La Roche Ltd. Pharmaceuticals Division, PDCO, Basel, Switzerland.
authors.forename: Eva
authors.initials: E
authors.lastname: Csinady
authors.affiliation: F. Hoffmann-La Roche Ltd. Pharmaceuticals, Biostatistics, Basel, Switzerland.
authors.forename: Nicola
authors.initials: N
authors.lastname: Moore
authors.affiliation: Centre Hospitalier Lyon-Sud, Lyon, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Coiffier
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000068258:Bevacizumab; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D000069283:Rituximab; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; C571759:R-CHOP protocol; D000068258:Bevacizumab; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone