Prostate cancer
Analysis of the Effect of Crossover From Placebo (PBO) to Darolutamide (DARO) on Overall Survival (OS) Benefit in the ARAMIS Trial
- Author(s)：
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Kazuhiro Suzuki1, Hiroji Uemura2, Neal Shore3, Karim Fizazi4, Teuvo Tammela5, Murilo Luz6, Manuel Philco Salas7,
Paul Ouellette Jr.8, Sergio Lago9, Diogo Bastos10, G Kenneth Jansz11, Oana Petrenciuc12, Christian Kappeler13,
Toni Sarapohja14, Matthew Smith15 - Affiliation(s)：
- 1Department of Urology, Graduate School of Medicine, Gunma University, 2Urology and Renal Transplantation, Medical center, Yokohama City University,3Carolina Urologic Research Center, Atlantic Urology Clinics, Myrtle Beach, SC, USA,4Institut Gustave Roussy, University of Paris-Saclay, Villejuif, France,5Tampere University Hospital and Tampere University, Tampere, Finland,6Hospital Erasto Gaertner, Curitiba, Brazil,7Instituto de Oncología y Radioterapia Clínica Ricardo Palma, Lima, Peru,8Recherches Cliniques TheraDev, Granby, QC, Canada,9Hospital São Lucas da PUCRS, RS, Brazil,10Hospital Sirio-Libanes, São Paulo, SP, Brazil,11Medicine Professional Corporation, Burlington, ON, Canada,12Bayer HealthCare Pharmaceuticals, Inc., Whippany, NJ, USA,13Bayer AG, Berlin, Germany,14Orion Pharma, Espoo, Finland,15Massachusetts General Hospital Cancer Center and Harvard Medical School, Urologic Oncology, Boston, MA, USA.
Background: DARO significantly prolonged metastasis-free survival and OS with a favorable safety profile in non-metastatic castration-resistant prostate cancer (nmCRPC) patients (pts) in ARAMIS (NCT0220061). Following unblinding, crossover from PBO to DARO was permitted for the subsequent open-label phase. Sensitivity analyses were performed to assess the effect of crossover on OS benefit.
Methods: Pts with nmCRPC receiving androgen deprivation therapy were randomized 2:1 to DARO (n=955) or PBO (n=554). Iterative parameter estimation (IPE) and rank-preserving structural failure time (RPSFT) analyses were performed as pre-planned sensitivity analyses to adjust for the treatment effect of crossover on OS.
Results: 170 pts (31%) crossed over from PBO to DARO; median treatment duration from unblinding to the final data cut-off was 11 months. Final analysis of the combined double-blind (DB) and open label periods conducted after 254 deaths showed a statistically significant OS benefit for DARO vs PBO (HR 0.69; 95%CI 0.53-0.88; P=0.003). Results from the IPE (HR 0.66; 95%CI 0.51-0.84; P<0.001) and RPSFT (HR 0.68; 95%CI 0.51-0.90; P=0.007) analyses were similar, showing the impact of crossover was small. DARO safety was favorable at the final analysis, and discontinuation rates at the end of the DB period remained unchanged from the primary analysis (8.9% DARO;8.7% PBO).
Conclusions: Treatment with DARO in men with nmCRPC is associated with significant improvement in OS regardless of pts crossing over from PBO to DARO. Safety of DARO remained favorable at the final analysis.
Flavio Mavignier Cárcano (Hospital de Câncer de Barretos, Brazil), Livia Andrade (Hospital Santa Izabel, Brazil), Marc Pliskin (The Urology Group, Cincinnati, USA), Nicolas Lazaretti (Hospital de Clínicas de Passo Fundo, Brazil), Larissa De Arruda (Instituto do Câncer do Ceará, Fortaleza), and Jose Jaime Correa (Hospital Pablo Tobon Uribe, Colombia) are included as co-authors in this presentation.
The efficacy of metastasis-directed radiation therapy (MDRT) for oligometastaticcastration-resistant prostate cancer (CRPC): multi-institutional retrospective study
- Author(s)：
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Akira Nagahara1, Soichiro Yoshida2, Makoto Ishii1, Akihiro Yoshimura1, Yoshiyuki Yamamoto1, Norihiko Kawamura1,
Yasutomo Nakai1, Masashi Nakayama1, Koji Konishi3, Kazuma Toda4, Ryoichi Yoshimura4, Yasuhisa Fujii2, Kazuo Nishimura1 - Affiliation(s)：
- 1Department of Urology, Osaka International Cancer Institute, 2Department of Urology, Graduate School, Tokyo Medical and Dental University,3Department of Radiation Oncology, Osaka International Cancer Institute,4Department of Radiation Therapeutics and Oncology, Graduate School, Tokyo Medical and Dental University
Background
We have utilized imaging study, especially whole-body magnetic resonance imaging (WB-MRI), to detect oligometastatic disease of castration-resistant prostate cancer (CRPC) and performed metastasis-directed radiation therapy (MDRT). We review our experience of MDRT for oligometastatic CRPC.
Methods
We retrospectively reviewed the database comprising 45 oligometastatic CRPC patients treated by MDRT combined with baseline androgen deprivation therapy in Osaka International Cancer Institute and Tokyo Medical and Dental University from January 2013 to March 2020. Diagnosis of oligometastatic disease was performed by computed tomography, bone scintigraphy and/or WB-MRI. Treatment efficacy of MDRT was assessed by change of serum prostate specific antigen (PSA) level and progression free survival (PFS). PFS was calculated by Kaplan-Meier method. Statistical analysis was performed with the log-rank test and Cox proportional hazard model analysis.
Results
The median age at treatment was 75 years (range, 62-89). The oligometastatic diseases were bone in 43 patients, lymph node in 4 patients and both in 2 patients. The number of treated lesions were as follows: 1 lesion for 35 patients, 2 lesions for 6 patients and 3 lesions for 4 patients. WB-MRI was performed in 34 patients (76%). Median RT dose was 35Gy (range, 30-60) for bone and 60Gy (range, 50-60) for lymph node. The median PSA prior MDRT was 7.6 ng/ml (range, 0.5-191) and PSA doubling time (PSADT) was 81 days. Post MDRT PSA reduction was observed in 39 patients (87%) and over 50% PSA reduction was observed in 27 patients (60%). Median PFS was 8.3 month and patients with over 81 days PSADT showed longer PFS (p=0.0025, log-rank test). Multivariate analysis showed over 81 days PSADT was significantly associated with longer PFS (p=0.0025).
Conclusions
Our data suggest that MDRT can achieve PSA reduction in most oligometastatic CRPC and PSADT could be a predictor of disease progression after MDRT.
