Prior therapies as prognostic factors of overall survival in metastatic castration-resistant prostate cancer patients treated with [177Lu]Lu-PSMA-617. A WARMTH multicenter study (the 617 trial).

The impact of prior therapies, especially chemotherapy, on overall survival (OS) in patients with castration-resistant prostate cancer (CRPC) receiving [177Lu]Lu-PSMA-617 therapy has been the subject of controversy. Therefore, WARMTH decided to plan a multicenter retrospective analysis (the "617 trial") to evaluate response rate and OS as well as the impact of prior therapies on OS in more than 300 patients treated with 177Lu-PSMA-617.

The data of 631 metastatic CRPC (mCRPC) patients from 11 different clinics were evaluated. According to the inclusion and exclusion criteria, all patients had to have received at least abiraterone or enzalutamide prior to [177Lu]Lu-PSMA-617 therapy. The patients were divided into three groups: patients who had received prior chemotherapy, patients who avoided chemotherapy, and patients for whom a chemotherapy was contraindicated.

The analysis included the data of 416 patients, with a median age of 71.9 years. At the time of analysis, 87 patients (20,9%) were still alive. A total of 53.6% of patients had received both abiraterone and enzalutamide; 75.5% and 26.4% had a history of chemotherapy with docetaxel and cabazitaxel, respectively. A total of 20.4% had had Ra-223. The median OS was 11.1 months. Prior chemotherapy, the existence of bone and liver metastases, as well as Eastern Cooperative Oncology Group (ECOG) status, were significant prognosticators of worse overall survival in both univariate and multivariate analyses. Patients without any prior chemotherapy showed a significantly longer OS (14.6 months). The median OS in patients who received one or two lines of chemotherapy with docetaxel or docetaxel followed by cabazitaxel, respectively, was 10.9 months and 8.9 months. There was no difference in OS between patients who had not received chemotherapy and patients for whom chemotherapy was contraindicated. The other prior therapies did not have any significant impact on OS.

In the present multicenter analysis, chemotherapy-naïve mCRPC patients receiving [177Lu]Lu-PSMA-617 therapy had a significantly longer OS than patients with a history of chemotherapy. This remained independent in the multivariate analysis besides presence of bone and liver metastases as negative prognosticators for survival, whereas an ECOG of 0-1 is associated with a longer OS.

European journal of nuclear medicine and molecular imaging. 2020 May 08 [Epub ahead of print]

Hojjat Ahmadzadehfar, Kambiz Rahbar, Richard P Baum, Robert Seifert, Katharina Kessel, Martin Bögemann, Harshad R Kulkarni, Jingjing Zhang, Carolin Gerke, Rolf Fimmers, Clemens Kratochwil, Hendrik Rathke, Harun Ilhan, Johanna Maffey-Steffan, Mike Sathekge, Levent Kabasakal, Francisco Osvaldo Garcia-Perez, Kalevi Kairemo, Masha Maharaj, Diana Paez, Irene Virgolini

Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany. ., Department of Nuclear Medicine, University Hospital Muenster, Muenster, Germany., Center for Radiomolecular Precision Oncology, Zentralklinik Bad Berka, Bad Berka, Germany., Department of Urology, University Hospital Münster, Muenster, Germany., Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany., Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany., Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany., Department of Nuclear Medicine, LMU, University Hospital Munich, Munich, Germany., Department of Nuclear Medicine, Medical University Innsbruck, Innsbruck, Austria., Department of Nuclear Medicine, University of Pretoria & Steve Biko Academic Hospital, Pretoria, South Africa., Department of Nuclear Medicine, Istanbul University, Istanbul, Turkey., Department of Nuclear Medicine and Molecular Imaging, Instituto Nacional de Cancerología Mexico City, Mexico City, Mexico., Docrates Cancer Center, Helsinki, Finland., Department of Nuclear Medicine, Imaging and Therapy Centre, Durban, KwaZulu-Natal, South Africa., Department of Nuclear Sciences and Applications, Nuclear Medicine and Diagnostic Imaging Section, IAEA, Vienna, Austria.