title: Safety and tolerability of etirinotecan pegol in advanced breast cancer: analysis of the randomized, phase 3 BEACON trial.
abstract: OBJECTIVE
  New treatments with novel mechanisms of action and non-overlapping toxicities are needed for patients with metastatic breast cancer. Etirinotecan pegol (EP) is a long-acting topoisomerase-I inhibitor with a unique toxicity profile. The randomized phase 3 BEACON study that compared EP to treatment of physician's choice (TPC) demonstrated its clinical activity. We now present detailed safety data from the BEACON trial.
  
  
  METHODS
  Patients with locally recurrent or metastatic breast cancer who had received at least two prior cytotoxic regimens for advanced disease were randomized to EP or TPC. Prior treatment with an anthracycline, a taxane and capecitabine was required. The frequencies of treatment-emergent AEs (TEAEs) and serious TEAEs were evaluated for the safety population, comprising all patients who received at least one dose of assigned treatment.
  
  
  RESULTS
  A total of 831 patients were evaluated (n = 425, EP; n = 406, TPC). Compared with TPC, EP was associated with a slightly higher median relative dose intensity (98.3 vs. 92.8 %, respectively) and significantly fewer grade ≥3 toxicities (48.0 vs. 63.1 %, P < 0.0001). The most commonly reported grade ≥3 toxicities in the EP arm were diarrhea (9.6 %) and neutropenia (9.6 %) and in the TPC arm, neutropenia (30.8 %). Median time to onset of grade ≥3 diarrhea was delayed with EP relative to TPC (43 vs. 7 days, respectively).
  
  
  CONCLUSIONS
  The differentiated mechanism of action of EP resulted in a safety profile that is substantially distinguished from that of current widely used therapies for the treatment of women with advanced breast cancer.
authors.affiliation: Ramon y Cajal University Hospital, Madrid, Spain ; Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron 119-129, Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Cortés
authors.affiliation: University of California, San Francisco, CA USA.
authors.forename: Hope S
authors.initials: HS
authors.lastname: Rugo
authors.affiliation: St. James's University Hospital, University of Leeds, Leeds, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Twelves
authors.affiliation: Medical Oncology Clinic, Jules Bordet Institute, Brussels, Belgium.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Awada
authors.affiliation: Mayo Clinic, Jacksonville, FL USA.
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
authors.affiliation: Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Seock-Ah
authors.initials: SA
authors.lastname: Im
authors.affiliation: Nektar Therapeutics, San Francisco, CA USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Nektar Therapeutics, San Francisco, CA USA.
authors.forename: Ute
authors.initials: U
authors.lastname: Hoch
authors.affiliation: Nektar Therapeutics, San Francisco, CA USA.
authors.forename: Denise
authors.initials: D
authors.lastname: Tomkinson
authors.affiliation: Nektar Therapeutics, San Francisco, CA USA.
authors.forename: James
authors.initials: J
authors.lastname: Buchanan
authors.affiliation: Nektar Therapeutics, San Francisco, CA USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Tagliaferri
authors.affiliation: Consultant, Sebastopol, CA USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Hannah
authors.affiliation: Baylor-Sammons Cancer Center, Texas Oncology, U.S. Oncology, Dallas, TX USA.
authors.forename: Joyce
authors.initials: J
authors.lastname: O'Shaughnessy
keywords: Chemotherapy safety; Chemotherapy side effects; Etirinotecan pegol; Metastatic breast cancer