title: Carboplatin and pegylated liposomal doxorubicin versus carboplatin and paclitaxel in very platinum-sensitive ovarian cancer patients: results from a subset analysis of the CALYPSO phase III trial.
abstract: OBJECTIVE
  To perform a subset analysis of patients with very platinum-sensitive recurrent ovarian cancer (ROC) enrolled in the phase III CALYPSO trial.
  
  
  METHODS
  The international non-inferiority trial enrolled women with ROC that relapsed >6 months following first- or second-line platinum- and paclitaxel-based therapies. Patients were randomised to CD [carboplatin-pegylated liposomal doxorubicin (PLD)] or CP (carboplatin-paclitaxel) and stratified by treatment-free interval (TFI). In this analysis, patients with a TFI>24 months were analysed separately for progression free survival (PFS), the primary endpoint of CALYPSO, overall survival (OS) and safety.
  
  
  RESULTS
  A total of 259 very platinum-sensitive patients were included (n=131, CD; n=128, CP). Median PFS was 12.0 months for the CD arm and 12.3 months for CP [HR=1.05 (95% CI, 0.79-1.40); P=0.73 for superiority] and median OS was 40.2 months for CD and 43.9 for CP [HR=1.18 (95% CI 0.85-1.63); P=0.33 for superiority]. Overall response rates were 42% and 38%, respectively (P=0.46). Toxicities were more common with CP versus CD, including grade 3/4 neutropenia (40.8% versus 27.5%; P=0.025), nausea (4.8% versus 3.1%; P=0.47), allergic reaction (8% versus 3.1%; P=0.082) sensory neuropathy (4.8% versus 2.3%; P=0.27) and grade 2 alopecia (88% versus 9.2%; P<0.001). Grade 3/4 thrombocytopenia (12.2% versus 3.2%; P=0.007) and mucositis (2.3% versus 0%; P=0.089) were more common with CD. Grade 3/4 hand-foot syndrome occurred rarely with CD (3 patients versus 0 in CP arm; P=0.089).
  
  
  CONCLUSIONS
  CP and CD were equally effective treatment regimens for patients with very platinum-sensitive ROC. The favourable risk-benefit profile suggests carboplatin-PLD as treatment of choice for these patients.
authors.affiliation: Arbeitsgemeinschaft Gynäkologische Onkologie, AGO Study Group (AGO) and University Medical Center Hamburg-Eppendorf, Germany. Electronic address: Sven.Mahner@gmx.de.
authors.forename: Sven
authors.initials: S
authors.lastname: Mahner
authors.affiliation: Arbeitsgemeinschaft Gynäkologische Onkologie, AGO Study Group (AGO) and Evangelisches Krankenhaus Düsseldorf, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Meier
authors.affiliation: Arbeitsgemeinschaft Gynäkologische Onkologie, AGO Study Group (AGO) and Kliniken Essen-Mitte, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: du Bois
authors.affiliation: ANZGOG-NHMRC, Sydney, Australia.
authors.forename: Chris
authors.initials: C
authors.lastname: Brown
authors.affiliation: Multicenter Italian Trials in Ovarian Cancer and gynecologic malignancies group (MITO) and Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Domenica
authors.initials: D
authors.lastname: Lorusso
authors.affiliation: Mario Negri Gynecologic Oncology Group (MANGO) and Ospedale San Gerardo, Monza, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Dell'Anna
authors.affiliation: Group d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO) and Clinique Valdegourue, Nimes, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Cretin
authors.affiliation: Nordic Society of Gynecological Oncology (NSGO) and Copenhagen University, Copenhagen, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Havsteen
authors.affiliation: National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG) and Universite de Sherbrooke, Sherbrooke, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Bessette
authors.affiliation: Arbeitsgemeinschaft Gynäkologische Onkologie Österreich (AGO-Austria) and Innsbruck University, Innsbruck, Austria.
authors.forename: Alain G
authors.initials: AG
authors.lastname: Zeimet
authors.affiliation: European Organisation for Research and Treatment of Cancer (EORTC) and University Hospital Leuven, Leuven, Belgium.
authors.forename: Ignace
authors.initials: I
authors.lastname: Vergote
authors.affiliation: Australia New Zealand Gynecological Oncology Group (ANZGOG) and Wesley Medical Centre, Brisbane, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Vasey
authors.affiliation: Group d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO) and Universite Paris Descartes, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Pujade-Lauraine
authors.affiliation: Group d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO) and Institut Claudius Regaud, Toulouse, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Gladieff
authors.affiliation: Mario Negri Gynecologic Oncology Group (MANGO) and Ospedale Ordine Mauriziano di Torino, Turin, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Ferrero
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016190:Carboplatin / Q000008:administration & dosage* / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000453:epidemiology; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000453:epidemiology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D017671:Platinum Compounds / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects; D012008:Recurrence
chemical_list: D017671:Platinum Compounds; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D016190:Carboplatin; D017239:Paclitaxel
keywords: CALYPSO; Carboplatin; Ovarian cancer; Paclitaxel; Pegylated liposomal doxorubicin; Very platinum-sensitive