(UroToday.com) On the first day of the American Society for Clinical Oncology (ASCO) Genitourinary Cancer Symposium 2023 focussing on prostate cancer, Dr. Ronan Flippot presented in Poster Session A on the efficacy of lutetium-177 PSMA (Lu-PSMA) in men with metastatic castration-resistant prostate cancer (mCRPC) previously treated with cabazitaxel.
Based on both the CARD and VISION trials, cabazitaxel and Lu-PSMA, respectively, demonstrate improved survival in patients with mCRPC after docetaxel and an androgen receptor pathway inhibitor (ARPI). However, there are outstanding questions regarding treatment sequencing but there is limited data regarding Lu-PSMA activity after cabazitaxel. We aimed at assessing activity of Lu-PSMA and determinants of outcomes in this setting.
The authors retrospectively enrolled consecutive mCRPC patients from 6 European centers who were treated with Lu-PSMA after cabazitaxel. They assessed a number of endpoints including radiographic progression-free survival (rPFS), time to PSA progression (PSA-TTP), PSA decline, objective response, overall survival, and safety.
Across the six sites, the authors enrolled 101 patients. The median age was 67 years. In terms of disease characteristics, 64% had ISUP grade 4-5 disease; 71% had bone or nodal (LN) metastases, 22% had visceral metastases, and 7% had LN only disease. DNA damage repair alterations (DDR) were found in 11/48 (23%) patients with available testing.
All patients had received previous docetaxel and 92% had received a prior ARPI (≥ 2 in 47%) before cabazitaxel. Patients had received a median number of 6 cabazitaxel cycles (range 1-26) and subsequently, patients received a median number of 3 Lu-PSMA cycles (range 1-14).
With a median follow-up of 5.7 months, the median rPFS from Lu-PSMA initiation was 4.3 months (95%CI 3.2-5.7) and median PSA-TTP was 3.5 months (95%CI 3.0-4.5).
Overall, 44 patients (44%) experienced a PSA decline ≥ 50% (PSA50), 54 (53%) had a PSA decline ≥ 30% (PSA30), and 67 (66%) any PSA decline. The objective response rate was 34%.
Baseline characteristics associated with shorter rPFS on Lu-PSMA included ISUP grade 4-5 disease (median rPFS of 3.5 vs. 7.2 months, p=0.02) and a time to castration resistance < 12 months (3.1 vs. 4.5 months, p=0.04). Patients with LN only had longer rPFS compared to those with bone and visceral metastases (median NR vs. 3.6 and 3.7 months, respectively, p=0.02). There was no association between activity of Lu-PSMA and DNA damage repair alterations, duration of previous cabazitaxel therapy, and number of previous ARPI. During Lu-PSMA, a profound PSA decline was associated with longer rPFS: patients achieving PSA50, PSA30 or any PSA decline had respective median rPFS rates of 9.0, 8.3 and 6.2 months, while those who did not experience any PSA decline had a median rPFS of only 2.6 months.
In conclusion, Lu-PSMA demonstrated substantial PSA decline but limited duration of response after cabazitaxel in a real-life setting. Adverse baseline characteristics and absence of PSA decline may help early identification of poor responders.
Presented by: Ronan Flippot, MD, Department of Medical Oncology, Gustave Roussy