Both cabazitaxel and lutetium-177 prostate-specific membrane antigen (Lu-PSMA) improve survival in metastatic castration-resistant prostate cancer (mCRPC) after an androgen receptor pathway inhibitor and docetaxel, but there are limited data regarding Lu-PSMA activity after cabazitaxel.
To assess the activity of Lu-PSMA and determinants of outcomes after cabazitaxel in mCRPC.
A retrospective analysis was conducted of consecutive mCRPC patients from eight European centers treated with Lu-PSMA after cabazitaxel.
Lu-PSMA every 6-8 wk at a dose of 6-7.6 GBq.
The primary endpoint was radiographic progression-free survival (rPFS). The secondary endpoints included time to prostate-specific antigen (PSA) progression (TTPSA), overall survival (OS), PSA decline, objective response rate (ORR), clinical benefit, and safety.
Of 126 patients, 68% had International Society of Urological Pathology (ISUP) grade 4-5 disease, 21% had visceral metastases, and 7% had lymph node disease only. DNA damage repair (DDR) alterations were detected in 11/50 (22%) patients with available testing. Patients received a median number of 3 Lu-PSMA cycles (interquartile range 2-4). With a median follow-up of 12.0 mo, the median rPFS was 4.4 mo (95% confidence interval [CI] 3.2-5.4), TTPSA 3.5 mo (95% CI 3.0-4.6), and OS 8.9 mo (95% CI 6.5-12.7). The ORR was 35%, and 55 patients (44%) experienced a PSA decline of ≥50%. The time to castration resistance of <12 mo was associated with shorter rPFS (p = 0.01). A similar trend was observed for ISUP grade 4-5 (p = 0.08), and baseline positron-emission tomography parameters including PSMA mean standardized uptake value (SUV) and maximum SUV (respectively, p = 0.06 and 0.05). The duration of previous cabazitaxel or DDR status did not impact outcomes. Patients experiencing a PSA decline of ≥ 50% on therapy demonstrated longer rPFS, TTPSA, and OS (all p < 0.0001). Limitations include retrospective data collection and investigator-based rPFS assessment.
Lu-PSMA demonstrated a substantial PSA decline but limited rPFS after cabazitaxel in a real-life setting. Adverse baseline characteristics, baseline positron-emission tomography parameters, and quality of PSA response may help identify patients less likely to benefit from Lu-PSMA.
Lutetium-177 prostate-specific membrane antigen (Lu-PSMA) improved outcomes in patients with castration-resistant prostate cancer, but there are limited data about its activity after cabazitaxel, a chemotherapy that is also the standard of care in this setting. We conducted a study across eight European centers and showed substantial responses on Lu-PSMA after cabazitaxel, although activity was short lived in a heavily pretreated population. Our findings prompt for real-life evaluation of Lu-PSMA in earlier settings to define the best therapeutic sequence.
European urology oncology. 2024 Apr 24 [Epub ahead of print]
Ronan Flippot, Tugce Telli, Maud Velev, Aude Fléchon, Manon De Vries-Brilland, Léa Turpin, Andries Bergman, Fabio Turco, Hakim Mahammedi, Wolfgang P Fendler, Anne-Laure Giraudet, Quentin Josset, Françoise Montravers, Wouter Vogel, Silke Gillessen, Simona Berardi Vilei, Ken Herrmann, David Kryza, Gaetano Paone, Boris Hadaschik, Charles Merlin, Pierre-Alban Dufour, Alice Bernard-Tessier, Natacha Naoun, Anna Patrikidou, Camilo Garcia, Stéphanie Foulon, Arnaud Pagès, Karim Fizazi
Department of Cancer Medicine, Gustave Roussy, Paris Saclay University, Villejuif, France. Electronic address: ., Department of Nuclear Medicine, University of Duisburg-Essen, Essen, Germany; German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany., Department of Cancer Medicine, Gustave Roussy, Paris Saclay University, Villejuif, France., Department of Medical Oncology, Centre Leon Berard, Lyon, France., Department of Medical Oncology, Institut de Cancérologie de l'Ouest, Angers, France., Department of Nuclear Medicine, Tenon University Hospital, Paris, France., Division of Medical Oncology, the Netherlands Cancer Institute, Amsterdam, The Netherlands., Istituto Oncologico della Svizzera Italiana, EOC, Bellinzona, Switzerland; Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland; Department of Oncology, at Division of Medical Oncology, San Luigi Gonzaga Hospital, University of Turin, Orbassano, Turin, Italy., Department of Medical Oncology, Centre Jean Perrin, Clermont-Ferrand, France., Department of Nuclear Medicine, Centre Leon Bérard, Lyon, France., Istituto Oncologico della Svizzera Italiana, EOC, Bellinzona, Switzerland; Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland., Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland; Clinic of Nuclear Medicine and Molecular Imaging, Imaging Institute of Southern Switzerland, EOC, Bellinzona, Switzerland., German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany; Department of Urology, University of Duisburg-Essen, Essen, Germany., Department of Nuclear Medicine, Centre Jean Perrin, Clermont-Ferrand, France., Department of Nuclear Medicine, Institut de Cancérologie de l'Ouest, Angers, France., Department of Nuclear Medicine, Gustave Roussy, Paris Saclay University, Villejuif, France., Department of Biostatistics and Epidemiology, INSERM UMR 1018 "Oncostat", Gustave Roussy, Paris Saclay University, Villejuif, France.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/38664139