Factors influencing clinical and biological response in patients treated with [177Lu]Lu-PSMA-617 under France's early access program

BackgroundVISION study showed that [177Lu]Lu-PSMA-617 (Lu-PSMA617) combined with BSoC prolonged imaging-based progression-free survival (PFS), overall survival, and delayed time to worsening in health-related quality of life, in PSMA-positive mCRPC patients (pts). Various factors related to pts may impact the treatment's effectiveness. This retrospective analysis aims to evaluate the influence of these factors on the clinical and biological response of pts receiving Lu-PSMA617 under France's early access program.MethodsPSMA positive mCRPC patients pretreated with 1-2 taxane chemotherapy and ≥1 novel hormonal therapy (NHT) received Lu-PSMA617. Responders (reduced PSA levels and improved clinical symptoms) and non-responders (PSA progression and/or worsening clinical symptoms) were compared using bivariate analysis (Chi-squared test, Fisher's exact test, or Mann-Whitney test). Odd ratios (OR) and their 95% confidence interval [95CI] were calculated. A p-value <0.05 was considered statistically significant.ResultsBetween 12/1/2021 and 4/30/2023, 685 pts were categorized as responders (311 pts) or non-responders (374 pts). Responders received more Lu-PSMA617 cycles (median 6 vs. 3; p<0.0001), showed more frequent uptake in all lesions on PSMA PET (85.2% vs. 69.5% of pts; OR 2.5 [95CI: 1.7, 3.7]; p<0.001), and received more frequently concurrent NHT (33.1% vs. 18.7%; OR 1.9 [95CI: 1.3, 2.7]; p<0.001). No significant differences (p>0.05) were observed with respect to patient age, ECOG score, initial PSA levels, metastasis locations, number of previous NHT or taxane chemotherapy, and concomitant treatments. Additionally, pts with PSMA PET uptake in all lesions had prolonged PFS (median 7.9 vs. 5.5 months (mo); p<0.001) and delayed symptom worsening (median 8.1 vs. 7.0 mo; p=0.046). Previous taxane chemotherapy correlated with delayed symptom worsening (8.2 vs 7.5 mo; p=0.007). Concurrent NHT was also associated with a longer PFS (median 8.3 vs. 6.1 mo; p=0.0001) and delayed time to symptom worsening (median 8.6 vs. 7.4 mo; p<0.001).ConclusionsResponse to Lu-PSMA617 may be influenced by PSMA-PET lesion positivity, concurrent NHT administration and the number of Lu-PSMA617 administered cycles.Legal entity responsible for the studyAAA - Advanced Accelerator Applications, a Novartis Company.FundingAAA - Advanced Accelerator Applications, a Novartis Company.DisclosureV. Habouzit: Financial Interests, Other: Sanofi, Sirtex, Boston Scientific, Pfizer. M. Claudin: Financial Interests, Other: AdAcAp-Novartis. C. BAILLY: Financial Interests, Other: Boston Scientific, AdAcAp-Novartis, Sirtex Medical, Telix Radiopharmaceuticals. P. Schwartz: Financial Interests, Other: AdAcAp-Novartis, Eisai. S. Chene: Financial Interests, Full or part-time Employment: AdAcAp-Novartis. K. Hebert: Financial Interests, Other: AdAcAp-Novartis, Astellas. All other authors have declared no conflicts of interest.