Real-world Outcomes of Sequential Androgen-receptor Targeting Therapies with or Without Interposed Life-prolonging Drugs in Metastatic Castration-resistant Prostate Cancer: Results from the Dutch Castration-resistant Prostate Cancer Registry.

Cross resistance between androgen-receptor targeting therapies (ARTs) (abiraterone acetate plus prednisone [ABI+P] or enzalutamide [ENZ]) for treatment of metastatic castration-resistant prostate cancer (mCRPC) may affect responses to second ART (ART2).

To establish treatment duration and prostate-specific antigen (PSA) response of ART2 in real-world mCRPC patients treated with or without other life-prolonging drugs (LPDs; ie, docetaxel, cabazitaxel, or radium-223) between ART1 and ART2.

Castration-resistant prostate cancer patients, diagnosed between 2010 and 2016 were retrospectively registered in Castration-resistant Prostate Cancer Registry (CAPRI). Patients treated with both ARTs were clustered into two subgroups: ART1>ART2 or ART1>LPD>ART2.

Outcomes were ≥50% PSA response and treatment duration of ART2. Descriptive statistics and binary logistic regression after multiple imputations were performed.

A total of 273 patients were included with a median follow-up of 8.4 mo from ART2. Patients with ART1>ART2 were older and had favourable prognostic characteristics at ART2 baseline compared with patients with ART1>LPD>ART2. No differences between ART1>ART2 and ART1>LPD>ART2 were found in PSA response and treatment duration. Multivariate analysis suggested that PSA response of ART2 was less likely in patients with visceral metastases (odds ratio [OR] 0.143, p=0.04) and more likely in patients with a relatively longer duration of androgen-deprivation treatment (OR 1.028, p=0.01) and with ABI + P before ENZ (OR 3.192, p=0.02). A major limitation of this study was missing data, a common problem in retrospective observational research.

The effect of ART2 seems to be low, with a low PSA response rate and a short treatment duration irrespective of interposed chemotherapy or radium-223, especially in patients with short time on castration, visceral disease, and ENZ before ABI+P.

We observed no differences in outcomes of patients treated with sequential abiraterone acetate plus prednisone (ABI+P) and enzalutamide (ENZ) with or without interposed chemotherapy or radium-223. In general, outcomes were lower than those in randomised trials, questioning the additional effect of second treatment with ABI+P or ENZ in daily practice.

European urology oncology. 2019 Oct 07 [Epub ahead of print]

Malou C P Kuppen, Hans M Westgeest, Alphonsus J M van den Eertwegh, Reindert J A van Moorselaar, Inge M van Oort, Juleon L L M Coenen, A C M Fons van den Bergh, Niven Mehra, Diederik M Somford, Andre M Bergman, Daan Ten Bokkel Huinink, Laurent Fossion, Maud M Geenen, Mathijs P Hendriks, Addy C M van de Luijtgaarden, Marco B Polee, Nir I Weijl, Agnes J van de Wouw, Ronald de Wit, Carin A Uyl-de Groot, Winald R Gerritsen

Institute for Medical Technology Assessment, Erasmus School of Health Policy and Management, Rotterdam, The Netherlands. Electronic address: ., Department of Internal Medicine, Amphia Hospital, Breda, The Netherlands., Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands., Department of Urology, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands., Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands., Department of Internal Medicine, Isala Klinieken, Zwolle, The Netherlands., Department of Radiation Oncology, University Medical Center Groningen, Groningen, The Netherlands., Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands., Department of Urology, Canisius Wilhemina Hospital, Nijmegen, The Netherlands., Division of Internal Medicine (MOD) and Oncogenomics, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands., Department of Internal Medicine, Diakonessenhuis, Utrecht, The Netherlands., Department of Urology, Maxima Medical Center, Eindhoven, The Netherlands., Department of Internal Medicine, OLVG, Amsterdam, The Netherlands., Department of Internal Medicine, Northwest Clinics, Alkmaar, The Netherlands., Department of Internal Medicine, Reinier de Graaf Groep, Delft, The Netherlands., Department of Internal Medicine, Medical Center Leeuwarden, Leeuwarden, The Netherlands., Department of Internal Medicine, MCH-Bronovo Hospital, 's-Gravenhage, The Netherlands., Department of Internal Medicine, VieCuri Medical Center, Venlo, The Netherlands., Department of Medical Oncology, Erasmus MC Daniel den Hoed Cancer Center, Rotterdam, The Netherlands., Institute for Medical Technology Assessment, Erasmus School of Health Policy and Management, Rotterdam, The Netherlands.