Details

Autor(en) / Beteiligte

• Flippot, Ronan
• Telli, Tugce
• Velev, Maud
• Fléchon, Aude
• De Vries-Brilland, Manon
• Turpin, Léa
• Bergman, Andries
• Turco, Fabio
• Mahammedi, Hakim
• Fendler, Wolfgang P.
• Giraudet, Anne-Laure
• Josset, Quentin
• Montravers, Françoise
• Vogel, Wouter
• Gillessen, Silke
• Berardi Vilei, Simona
• Herrmann, Ken
• Kryza, David
• Paone, Gaetano
• Hadaschik, Boris
• Merlin, Charles
• Dufour, Pierre-Alban
• Bernard-Tessier, Alice
• Naoun, Natacha
• Patrikidou, Anna
• Garcia, Camilo
• Foulon, Stéphanie
• Pagès, Arnaud
• Fizazi, Karim

Titel

Activity of Lutetium-177 Prostate-specific Membrane Antigen and Determinants of Outcomes in Patients with Metastatic Castration-resistant Prostate Cancer Previously Treated with Cabazitaxel: The PACAP Study

Ist Teil von

• European urology oncology, 2024-10, Vol.7 (5), p.1132-1140

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• Lutetium-177 prostate-specific membrane antigen (PSMA) after cabazitaxel provides only short-lived activity despite substantial rates of prostate-specific antigen (PSA) decline in an all-comer population. Baseline disease characteristics, positron-emission tomography parameters, and quality of PSA decline can help identify patients likely to benefit from lutetium-177 PSMA. 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.