title: Final overall survival results of a randomized trial comparing bortezomib plus pegylated liposomal doxorubicin with bortezomib alone in patients with relapsed or refractory multiple myeloma.
abstract: BACKGROUND
  Previous results from an interim analysis of an open-label, randomized, phase 3 study demonstrated that bortezomib combined with pegylated liposomal doxorubicin (PLD) was superior to bortezomib monotherapy in patients with relapsed/refractory multiple myeloma who had previously received one or more lines of therapy. Protocol-defined final survival data from that study are provided here.
  
  
  METHODS
  Patients were randomized (1:1) to receive either bortezomib alone (1.3 mg/m(2) intravenously on days 1, 4, 8, and 11 of every 21-day cycle) or bortezomib-PLD (bortezomib plus PLD 30 mg/m(2) intravenously on day 4). The primary endpoint was the time to progression. Secondary efficacy endpoints included overall survival (OS), progression-free survival, and the overall response rate.
  
  
  RESULTS
  In total, 646 patients (bortezomib-PLD, n = 324; bortezomib alone, n = 322) were randomized between December, 2004, and March, 2006. On the clinical cutoff date (May 16, 2014) for the final survival analysis, at a median follow-up of 103 months, 79% of patients had died (bortezomib-PLD group: 253 of 324 patients; 78%; bortezomib alone group: 257 of 322 patients; 80%). The median OS in the bortezomib-PLD group was 33 months (95% confidence interval [CI], 28.9-37.1) versus 30.8 months (95% CI, 25.2-36.5) in the bortezomib alone group (hazard ratio, 1.047; 95% CI, 0.879-1.246; P = .6068). Salvage therapies included conventional and novel drugs, which were well balanced between the two treatment groups.
  
  
  CONCLUSIONS
  Despite inducing a superior time to progression, long-term follow-up revealed that PLD-bortezomib did not improve OS compared with bortezomib alone in patients with relapsed/refractory multiple myeloma. The inability to sustain the early observed survival advantage may have been caused by the effects of subsequent lines of therapy, and underscores the need for long-term follow-up of phase 3 trials while recognizing the challenge of having adequate power to detect long-term differences in OS. Cancer 2016;122:2050-6. © 2016 American Cancer Society.
authors.affiliation: Department of Lymphoma/Myeloma, The University of Texas, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Robert Z
authors.initials: RZ
authors.lastname: Orlowski
authors.affiliation: Division of Hematology, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
authors.affiliation: Department of Hematology, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: Sonneveld
authors.affiliation: Department of Clinical Hematology, August Pi I Sunyer Biomedical Research Institute, University of Barcelona, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Bladé
authors.affiliation: Department of Hemato-Oncology, University Hospital and Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic.
authors.forename: Roman
authors.initials: R
authors.lastname: Hajek
authors.affiliation: Malignant Hematology and Stem Cell Transplantation Service, The Alfred Hospital, Melbourne, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Spencer
authors.affiliation: Department of Hematology, Medical University of Łódź, Łódź, Poland.
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Robak
authors.affiliation: Hematology and Bone Marrow Transplant Department, Medical University of Lublin, Lublin, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Dmoszynska
authors.affiliation: Department of Hematology, Royal Adelaide Hospital, West Australia, Australia.
authors.forename: Noemi
authors.initials: N
authors.lastname: Horvath
authors.affiliation: Department of Internal Medicine, Charles University General Faculty Hospital, Prague, Czech Republic.
authors.forename: Ivan
authors.initials: I
authors.lastname: Spicka
authors.affiliation: Division of Hematology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Sutherland
authors.affiliation: Department of Hematology, First Republican Clinical Hospital of the Ministry of Healthcare of the Udmurt Republic, Izhevsk, Russia.
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Suvorov
authors.affiliation: Janssen Research & Development, LLC, Raritan, New Jersey.
authors.forename: Liang
authors.initials: L
authors.lastname: Xiu
authors.affiliation: Janssen Research & Development, LLC, Raritan, New Jersey.
authors.forename: Andrew
authors.initials: A
authors.lastname: Cakana
authors.affiliation: Janssen Research & Development, LLC, Raritan, New Jersey.
authors.forename: Trilok
authors.initials: T
authors.lastname: Parekh
authors.affiliation: Center for Applied Medical Research, August Pi I Sunyer Biomedical Research Institute, University of Navarra, Pamplona, Spain.
authors.forename: Jesús F
authors.initials: JF
authors.lastname: San-Miguel
mesh_terms: D061605:Administration, Intravenous; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D000069286:Bortezomib / Q000008:administration & dosage* / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D000069286:Bortezomib; D004317:Doxorubicin
keywords: bortezomib; doxorubicin; multiple myeloma; pegylated liposomal doxorubicin; survival