% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{Fizazi:303005, author = {K. Fizazi and K. N. Chi and N. D. Shore and V. Herrmann$^*$ and J. S. de Bono and D. Castellano and J. M. Piulats and A. Fléchon and X. X. Wei and H. Mahammedi and G. Roubaud and M. Fleming and T. Haas and S. Ghebremariam and T. N. Kreisl and S. Rajagopalan and O. Sartor and M. J. Morris}, collaboration = {P. Investigators}, title = {{F}inal overall survival and safety analyses of the phase 3 {PSMA}fore trial of [177{L}u]{L}u-{PSMA}-617 versus change of androgen receptor pathway inhibitor in taxane-naive patients with metastatic castration-resistant prostate cancer.}, journal = {Annals of oncology}, volume = {nn}, issn = {0923-7534}, address = {Amsterdam [u.a.]}, publisher = {Elsevier}, reportid = {DKFZ-2025-01452}, pages = {nn}, year = {2025}, note = {epub}, abstract = {In PSMAfore, [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) prolonged radiographic progression-free survival (rPFS) in taxane-naive patients with metastatic castration-resistant prostate cancer (mCRPC), with a favourable safety profile, versus a change in androgen receptor pathway inhibitor (ARPI). We report the final overall survival (OS) analysis and updated safety data.PSMAfore (NCT04689828) was an open-label, international, phase 3 trial. Patients with prostate-specific membrane antigen (PSMA)-positive mCRPC who had experienced disease progression once on a previous ARPI and were candidates for ARPI change were randomized 1:1 to 177Lu-PSMA-617 or ARPI change to abiraterone or enzalutamide. Crossover from ARPI change to 177Lu-PSMA-617 was allowed after centrally confirmed radiographic progression. Endpoints included rPFS (primary), OS (key secondary), and safety (secondary).Patients were randomized to 177Lu-PSMA-617 or ARPI change (n = 234 each): 141/234 participants $(60.3\%)$ randomized to ARPI change crossed over $(75.4\%$ of those with centrally confirmed radiographic progression). The median OS was 24.48 months $(95\%$ CI 19.55-28.94) with 177Lu-PSMA-617 versus 23.13 (19.61-25.53) with ARPI change (hazard ratio [HR] 0.91 $[95\%$ CI 0.72-1.14]; p = 0.20) based on the intention-to-treat (ITT) principle; the crossover-adjusted OS HR by inverse probability of censoring weighting modelling was 0.59 $(95\%$ CI 0.38-0.91). For 177Lu-PSMA-617 versus ARPI change, exposure-adjusted incidences of grade ≥ 3 and serious treatment-emergent adverse events were 60.8 versus 85.1 and 32.5 versus 49.9 per 100 patient-treatment years, respectively. Dry mouth occurred in 135/227 participants $(59.5\%;$ 2/227 grade ≥ 3) and anaemia in 62/227 $(27.3\%;$ 14/227 grade ≥ 3) in the 177Lu-PSMA-617 arm.OS analyses did not show a statistically significant difference between the 177Lu-PSMA-617 and ARPI arms based on the ITT principle; results were likely confounded by the high rate of crossover. The safety profile of 177Lu-PSMA-617 was favourable with no new safety signals identified.}, keywords = {(177)Lu-PSMA-617 (Other) / Metastatic castration-resistant prostate cancer (Other) / overall survival (Other) / radioligand therapy (Other) / safety (Other) / taxane-naive (Other)}, cin = {ED01}, ddc = {610}, cid = {I:(DE-He78)ED01-20160331}, pnm = {899 - ohne Topic (POF4-899)}, pid = {G:(DE-HGF)POF4-899}, typ = {PUB:(DE-HGF)16}, pubmed = {pmid:40680993}, doi = {10.1016/j.annonc.2025.07.003}, url = {https://inrepo02.dkfz.de/record/303005}, }