Survival Outcomes From a Cumulative Analysis of Worldwide Observational Studies on Sequential Use of New Agents in Metastatic Castration-Resistant Prostate Cancer.

The sequential use of a number of new agents (NAs) have improved the overall survival (OS) of patients with metastatic castration-resistant prostate cancer whose disease progresses after docetaxel (DOC) treatment. The aim of this study was to assess the cumulative survival outcomes of different sequencing strategies by evaluating the individual data from published studies of patients treated with a post-DOC treatment sequence of 2 NAs.

The patients' individual data were analyzed to investigate whether different sequencing strategies lead to differences in OS.

We analyzed the data of 1099 evaluable patients. Among the patients treated with a second-line new hormone agent (NHA), median OS from the start of third-line treatment was significantly longer in the patients treated with cabazitaxel (CABA) than in those treated with abiraterone acetate or enzalutamide. Median cumulative OS (cumOS) from the start of second-line treatment was 21.1 months in the patients who received NHA then NHA, 22.1 months in those who received NHA then CABA, and 21.0 months in those who received CABA then NHA. Among the patients with a second-line progression-free survival of ≥6 months, median cumOS was significantly longer in patients who received CABA-including sequences than in those treated with NHA then NHA sequences (29.5 vs. 24.8 months; P = .03).

Our findings suggest that the sequential use of NAs with different mechanisms of action improves cumOS regardless of the order in which they are administered, thus supporting the hypothesis of cross-resistance between the 2 NHAs.

Clinical genitourinary cancer. 2019 Sep 27 [Epub ahead of print]

Orazio Caffo, Michel Wissing, Diletta Bianchini, Andries Bergman, Frederik B Thomsen, Sebastian Schmid, Evan Y Yu, Evangelos Bournakis, Avishay Sella, Vittorina Zagonel, Ugo De Giorgi, Marcello Tucci, Hans Gelderblom, Luca Galli, Giovanni Pappagallo, Emilio Bria, Isabella Sperduti, Stephane Oudard, CASTOR study investigators

Medical Oncology Department, Santa Chiara Hospital, Trento, Italy. Electronic address: ., Medical Oncology Department, University Medical Centre, Leiden, the Netherlands., Division of Clinical Studies, Prostate Cancer Targeted Therapies Group, Royal Marsden NHS Foundation Trust, Sutton, United Kingdom., Division of Internal Medicine (MOD) and Oncogenomics, Netherlands Cancer Institute, Amsterdam, the Netherlands., Copenhagen Prostate Cancer Center, Rigshospitalet, Copenhagen, Denmark., Klinik und Poliklinik für Urologie, Klinikum rechts der Isar der Technischen Universität München, München, Germany., Department of Medicine, University of Washington School of Medicine, Seattle, WA., Oncology Department, ARETAIEIO University Hospital of Athens, IASO General Clinic of Athens, Athens, Greece., Department of Oncology, Yitzhak Shamir Medical Center, Assaf Harofe Campus Harofeh Medical Center, Sackler School of Medicine, Tel-Aviv, Israel., Medical Oncology Department, Istituto Oncologico Veneto, Padua, Italy., Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy., Medical Oncology Department, Azienda Ospedaliera Universitaria S. Luigi Gonzaga, Orbassano, Italy., Medical Oncology Department, Azienda Ospedaliera Universitaria, Pisa, Italy., Epidemiology & Clinical Trials Office, General Hospital, Mirano, Italy., Oncology Unit, Università Cattolica del Sacro Cuore, Fondazione Policlinico "A. Gemelli", Rome, Italy., Biostatistical Unit, Regina Elena National Cancer Institute, Rome, Italy., Service de cancérologie médicale, Hôpital Européen Georges Pompidou, René Descartes University, Paris, France.