{"entity":{"id":"docetaxel-then-lu177-psma","kind":"pairing","name":"Docetaxel (taxane chemotherapy) then 177Lu-PSMA-617","aka":[],"tldr":"In the trial that got 177Lu-PSMA-617 (Pluvicto) approved, everyone had already been treated with a taxane chemotherapy drug like docetaxel and with a hormone pill first. That is the treatment order the approval is based on, though a newer trial is now testing whether Pluvicto can be used earlier, before chemotherapy.","summary":"The pivotal VISION trial (NCT03511664; Sartor et al., NEJM 2021) that supported FDA and EMA approval of 177Lu-PSMA-617 (Pluvicto) enrolled adults with metastatic castration-resistant prostate cancer who had already progressed on at least one androgen-receptor pathway inhibitor (for example abiraterone or enzalutamide) and on one or two prior taxane-based chemotherapy regimens, typically docetaxel. Patients also had to have PSMA-positive disease on centrally read 68Ga-PSMA-11 PET-CT, with no qualifying PSMA-negative lesions. 177Lu-PSMA-617 (7.4 GBq every 6 weeks, up to 6 cycles) plus protocol-permitted standard care was compared with standard care alone; median overall survival was 15.3 months versus 11.3 months (hazard ratio 0.62, 95% CI 0.52-0.74, p<0.001).\n\nBecause prior taxane exposure was a trial entry requirement rather than a randomised comparison of sequencing strategies, VISION establishes an evidence-based treatment order — androgen-receptor pathway inhibitor, then taxane chemotherapy (commonly docetaxel), then 177Lu-PSMA-617 — rather than proving that giving the radioligand therapy after docetaxel is better than giving it before. Retrospective subgroup analyses of VISION found that survival benefit from 177Lu-PSMA-617 was preserved regardless of whether patients had received one or two prior taxane regimens, and regardless of the number of prior androgen-receptor pathway inhibitors.\n\nThis sequencing question is now being tested directly: the phase 3 PSMAfore trial (NCT04689828) enrolled taxane-naive patients progressing after one androgen-receptor pathway inhibitor and randomised them to 177Lu-PSMA-617 or to switching to a different androgen-receptor pathway inhibitor, explicitly to establish whether radioligand therapy can move earlier in the treatment sequence, ahead of chemotherapy, rather than only being used after it.","asOf":"2026-09-22","links":[{"label":"Sartor et al., VISION primary results, N Engl J Med 2021 (full text)","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa2107322"},{"label":"JNM commentary on VISION eligibility criteria (prior taxane and ARPI requirements)","url":"https://jnm.snmjournals.org/content/63/6/823"},{"label":"PSMAfore design (taxane-naive, ARPI-progressed population), ASCO 2022","url":"https://ascopubs.org/doi/10.1200/JCO.2022.40.6_suppl.TPS211"}],"tags":["prostate cancer","treatment sequencing","radioligand therapy"],"related":["prostate-mcrpc","vision","psmafore","paper-vision-nejm-2021","michael-morris","oliver-sartor","ga-68","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"docetaxel","b":"pluvicto","rationale":"The approval of 177Lu-PSMA-617 rests on a trial population defined by prior treatment order (hormone therapy, then taxane chemotherapy, then radioligand therapy), so this is the evidence-based sequence rather than a proven optimal one.","evidence":"VISION (n=831) required progression after at least one androgen-receptor pathway inhibitor and one or two taxane regimens (typically docetaxel) before enrolment; median overall survival with added 177Lu-PSMA-617 was 15.3 vs 11.3 months (HR 0.62, p<0.001) (Sartor et al., NEJM 2021). PSMAfore (NCT04689828) is testing whether the radioligand therapy can instead be used before taxane chemotherapy.","pairingType":"sequence"},"route":"/pairings/docetaxel-then-lu177-psma/","neighbours":{"indication":[{"id":"prostate-mcrpc","kind":"indication","name":"Metastatic castration-resistant prostate cancer","route":"/indications/prostate-mcrpc/"}],"trial":[{"id":"psmafore","kind":"trial","name":"PSMAfore","route":"/trials/psmafore/"},{"id":"vision","kind":"trial","name":"VISION","route":"/trials/vision/"}],"paper":[{"id":"paper-vision-nejm-2021","kind":"paper","name":"VISION: lutetium-177 PSMA-617 radioligand therapy extends survival in advanced prostate cancer","route":"/key-papers/paper-vision-nejm-2021/"}],"person":[{"id":"oliver-sartor","kind":"person","name":"A. Oliver Sartor","route":"/people/oliver-sartor/"},{"id":"michael-morris","kind":"person","name":"Michael J. Morris","route":"/people/michael-morris/"}],"isotope":[{"id":"ga-68","kind":"isotope","name":"Gallium-68","route":"/isotopes/ga-68/"},{"id":"lu-177","kind":"isotope","name":"Lutetium-177","route":"/isotopes/lu-177/"}],"drug":[{"id":"docetaxel","kind":"drug","name":"Docetaxel","route":"/drugs/docetaxel/"},{"id":"pluvicto","kind":"drug","name":"Lutetium-177 vipivotide tetraxetan","route":"/drugs/pluvicto/"}]}}