{"entity":{"id":"paper-psmafore-lancet-2024","kind":"paper","name":"PSMAfore: 177Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor in taxane-naive mCRPC","aka":[],"tldr":"In men with advanced prostate cancer who had not yet had chemotherapy but whose disease had grown on one hormone-blocking drug, switching to the radioactive PSMA treatment kept the cancer under control for longer than switching to a different hormone drug.","summary":"PSMAfore was a phase 3, randomised, controlled, open-label trial at 74 sites in Europe and North America. Taxane-naive men with PSMA-positive metastatic castration-resistant prostate cancer who had progressed once on an androgen receptor pathway inhibitor (ARPI) were randomised 1:1 to 177Lu-PSMA-617 (7.4 GBq every 6 weeks for six cycles) or a change of ARPI (abiraterone or enzalutamide). Crossover to 177Lu-PSMA-617 was permitted after confirmed radiographic progression on ARPI change. The primary endpoint was radiographic progression-free survival (rPFS).\n\nOf 468 randomised men, updated analysis (median follow-up ~24 months) showed median rPFS of 11.6 months with 177Lu-PSMA-617 versus 5.6 months with ARPI change (HR 0.49, 95% CI 0.39-0.61). The final overall survival analysis (Ann Oncol 2025) found no significant intention-to-treat difference (24.5 vs 23.1 months, HR 0.91, p=0.20), heavily confounded by a 60% crossover rate from the control arm; a crossover-adjusted analysis suggested benefit (HR 0.59). Grade 3+ and serious adverse events were less frequent with 177Lu-PSMA-617 than with ARPI change.\n\nPSMAfore moved PSMA radioligand therapy earlier in the treatment sequence - before chemotherapy - and was the evidentiary basis, alongside VISION, for regulators to consider extending 177Lu-PSMA-617 use to the pre-taxane setting.","asOf":"2026-09-22","links":[{"label":"PubMed: PSMAfore primary results (Lancet 2024)","url":"https://pubmed.ncbi.nlm.nih.gov/39293462/"},{"label":"PubMed: PSMAfore final overall survival (Ann Oncol 2025)","url":"https://pubmed.ncbi.nlm.nih.gov/40680993/"}],"tags":["prostate cancer","radioligand therapy","randomised trial"],"related":["psmafore","vision","pluvicto","psma-pet","prostate-mcrpc","arpi","michael-morris","ken-herrmann","oliver-sartor","karim-fizazi","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Lancet","year":2024,"doi":"10.1016/S0140-6736(24)01653-2","pmid":"39293462","authors":"Morris MJ, Castellano D, Herrmann K, de Bono JS, Shore ND, et al.","paperType":"rct","findings":["Updated analysis: median rPFS 11.6 months (177Lu-PSMA-617) vs 5.6 months (ARPI change); HR 0.49 (95% CI 0.39-0.61).","Primary analysis: median rPFS 9.3 months vs 5.55 months; HR 0.41 (95% CI 0.29-0.56), p<0.0001.","Final overall survival (intention to treat): 24.48 vs 23.13 months, HR 0.91 (95% CI 0.72-1.14), p=0.20; crossover-adjusted HR 0.59 (95% CI 0.38-0.91).","60.3% of men assigned to ARPI change crossed over to 177Lu-PSMA-617 after progression.","Grade 3+ treatment-emergent adverse events: 60.8 per 100 patient-treatment years (177Lu-PSMA-617) vs 85.1 (ARPI change)."],"whatItMeans":"For men who still have a working hormone treatment option but whose cancer is progressing, offering the PSMA radioligand therapy sooner - before chemotherapy - delayed disease progression, though it did not clearly extend how long men lived once the very high rate of patients switching over is accounted for.","caveats":["Open-label design and high crossover from control to experimental arm make the overall-survival comparison unreliable by intention to treat.","Crossover-adjusted survival analyses rely on modelling assumptions rather than randomisation.","Trial excluded men who had already had a taxane, so results do not generalise to post-chemotherapy patients (that population is VISION and TheraP)."],"changedPractice":true,"participants":468},"route":"/key-papers/paper-psmafore-lancet-2024/","neighbours":{"trial":[{"id":"psmafore","kind":"trial","name":"PSMAfore","route":"/trials/psmafore/"},{"id":"vision","kind":"trial","name":"VISION","route":"/trials/vision/"}],"drug":[{"id":"pluvicto","kind":"drug","name":"Lutetium-177 vipivotide tetraxetan","route":"/drugs/pluvicto/"}],"technology":[{"id":"psma-pet","kind":"technology","name":"PSMA PET","route":"/technologies/psma-pet/"}],"indication":[{"id":"prostate-mcrpc","kind":"indication","name":"Metastatic castration-resistant prostate cancer","route":"/indications/prostate-mcrpc/"}],"term":[{"id":"arpi","kind":"term","name":"Androgen receptor pathway inhibitor (ARPI)","route":"/terms/arpi/"}],"person":[{"id":"oliver-sartor","kind":"person","name":"A. Oliver Sartor","route":"/people/oliver-sartor/"},{"id":"karim-fizazi","kind":"person","name":"Karim Fizazi","route":"/people/karim-fizazi/"},{"id":"ken-herrmann","kind":"person","name":"Ken Herrmann","route":"/people/ken-herrmann/"},{"id":"michael-morris","kind":"person","name":"Michael J. Morris","route":"/people/michael-morris/"}],"isotope":[{"id":"lu-177","kind":"isotope","name":"Lutetium-177","route":"/isotopes/lu-177/"}]}}