title: Addressing the expected survival benefit for clinical trial design in metastatic castration-resistant prostate cancer: Sensitivity analysis of randomized trials.
abstract: We performed a sensitivity analysis, cumulating all randomized clinical trials (RCTs) in which patients with metastatic castration-resistant prostate cancer (mCRPC) received systemic therapy, to evaluate if the comparison of RCTs may drive to biased survival estimations. An overall survival (OS) significant difference according to therapeutic strategy was more likely be determined in RCTs evaluating hormonal drugs versus those studies testing immunotherapy, chemotherapy or other strategies. With regard to control arm, an OS significant effect was found for placebo-controlled trials versus studies comparing experimental treatment with active therapies. Finally, regarding to docetaxel (DOC) timing, the OS benefit was more likely to be proved in Post-DOC setting in comparison with DOC and Pre-DOC. These data suggest that clinical trial design should take into account new benchmarks such as the type of treatment strategy, the choice of the comparator and the phase of the disease in relation to the administration of standard chemotherapy.
authors.affiliation: Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy. Electronic address: fmassari79@gmail.com.
authors.forename: Francesco
authors.initials: F
authors.lastname: Massari
authors.affiliation: Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy. Electronic address: alessandra.modena@alice.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Modena
authors.affiliation: Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy. Electronic address: ciccarese.c@gmail.com.
authors.forename: Chiara
authors.initials: C
authors.lastname: Ciccarese
authors.affiliation: Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy. Electronic address: sara.pilotto.85@alice.it.
authors.forename: Sara
authors.initials: S
authors.lastname: Pilotto
authors.affiliation: Medical Oncology, Santa Chiara Hospital, Trento, Italy. Electronic address: francesca.maines@gmail.com.
authors.forename: Francesca
authors.initials: F
authors.lastname: Maines
authors.affiliation: Medical Oncology, Ospedale San Donato, Istituto Toscano Tumori, Arezzo, Italy. Electronic address: sergio.bracarda@usl8.toscana.it.
authors.forename: Sergio
authors.initials: S
authors.lastname: Bracarda
authors.affiliation: Biostatistics, Regina Elena National Cancer Institute, Roma, Italy. Electronic address: isperduti@yahoo.it.
authors.forename: Isabella
authors.initials: I
authors.lastname: Sperduti
authors.affiliation: Biostatistics, Regina Elena National Cancer Institute, Roma, Italy. Electronic address: giannarelli@ifo.it.
authors.forename: Diana
authors.initials: D
authors.lastname: Giannarelli
authors.affiliation: Medical Oncology, Regina Elena National Cancer Institute, Roma, Italy. Electronic address: paolo_carlini@yahoo.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Carlini
authors.affiliation: Medical Oncology, Policlinico Universitario Campus Bio-Medico, Roma, Italy. Electronic address: d.santini@unicampus.it.
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.affiliation: Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy. Electronic address: giampaolo.tortora@univr.it.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Tortora
authors.affiliation: Medical Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. Electronic address: c.porta@smatteo.pv.it.
authors.forename: Camillo
authors.initials: C
authors.lastname: Porta
authors.affiliation: Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy. Electronic address: emilio.bria@univr.it.
authors.forename: Emilio
authors.initials: E
authors.lastname: Bria
mesh_terms: D002986:Clinical Trials as Topic; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016032:Randomized Controlled Trials as Topic; D012107:Research Design
keywords: Chemotherapy; Hormonal therapy; Immunotherapy; Overall survival; Prostate cancer