177Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor therapy for taxane-naive patients with progressive metastatic castration-resistant prostate cancer (PSMAfore): a phase 3, randomised, controlled trial.
Saved in:
| Title: | 177Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor therapy for taxane-naive patients with progressive metastatic castration-resistant prostate cancer (PSMAfore): a phase 3, randomised, controlled trial. |
|---|---|
| Authors: | Morris, Michael J (AUTHOR), Castellano, Daniel (AUTHOR), Herrmann, Ken (AUTHOR), de Bono, Johann S (AUTHOR), Shore, Neal D (AUTHOR), Chi, Kim N (AUTHOR), Crosby, Michael (AUTHOR), Piulats, Josep M (AUTHOR), Fléchon, Aude (AUTHOR), Wei, Xiao X (AUTHOR), Mahammedi, Hakim (AUTHOR), Roubaud, Guilhem (AUTHOR), Študentová, Hana (AUTHOR), Nagarajah, James (AUTHOR), Mellado, Begoña (AUTHOR), Montesa-Pino, Álvaro (AUTHOR), Kpamegan, Euloge (AUTHOR), Ghebremariam, Samson (AUTHOR), Kreisl, Teri N (AUTHOR), Wilke, Celine (AUTHOR) |
| Source: | Lancet. 9/28/2024, Vol. 404 Issue 10459, p1227-1239. 13p. |
| Subjects: | Prostate-specific membrane antigen, Castration-resistant prostate cancer, Androgen receptors, Progression-free survival, Overall survival, Medical screening |
| Abstract: | [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) prolongs radiographic progression-free survival and overall survival in patients with metastatic castration-resistant prostate cancer previously treated with androgen receptor pathway inhibitor (ARPI) and taxane therapy. We aimed to investigate the efficacy of 177Lu-PSMA-617 in patients with taxane-naive metastatic castration-resistant prostate cancer. In this phase 3, randomised, controlled trial conducted at 74 sites across Europe and North America, taxane-naive patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer who had progressed once on a previous ARPI were randomly allocated (1:1) to open-label, intravenous 177Lu-PSMA-617 at a dosage of 7·4 GBq (200 mCi) ± 10% once every 6 weeks for six cycles, or a change of ARPI (to abiraterone or enzalutamide, administered orally on a continuous basis per product labelling). Crossover from ARPI change to 177Lu-PSMA-617 was allowed after centrally confirmed radiographic progression. The primary endpoint was radiographic progression-free survival, defined as the time from randomisation until radiographic progression or death, assessed in the intention-to-treat population. Safety was a secondary endpoint. This study is registered with ClinicalTrials.gov (NCT04689828) and is ongoing. In this primary report of the study, we present primary (first data cutoff) and updated (third data cutoff) analyses of radiographic progression-free survival; all other data are based on the third data cutoff. Overall, of the 585 patients screened, 468 met all eligibility criteria and were randomly allocated between June 15, 2021 and Oct 7, 2022 to receive 177Lu-PSMA-617 (234 [50%] patients) or ARPI change (234 [50%]). Baseline characteristics were mostly similar between groups; median number of 177Lu-PSMA-617 cycles was 6·0 (IQR 4·0–6·0). Of patients assigned to ARPI change, 134 (57%) crossed over to receive 177Lu-PSMA-617. In the primary analysis (median time from randomisation to first data cutoff 7·26 months [IQR 3·38–10·55]), the median radiographic progression-free survival was 9·30 months (95% CI 6·77–not estimable) in the 177Lu-PSMA-617 group versus 5·55 months (4·04–5·95) in the ARPI change group (hazard ratio [HR] 0·41 [95% CI 0·29–0·56]; p<0·0001). In the updated analysis at time of the third data cutoff (median time from randomisation to third data cutoff 24·11 months [IQR 20·24–27·40]), median radiographic progression-free survival was 11·60 months (95% CI 9·30–14·19) in the 177Lu-PSMA-617 group versus 5·59 months (4·21–5·95) in the ARPI change group (HR 0·49 [95% CI 0·39–0·61]). The incidence of grade 3–5 adverse events was lower in the 177Lu-PSMA-617 group (at least one event in 81 [36%] of 227 patients; four [2%] grade 5 [none treatment related]) than the ARPI change group (112 [48%] of 232; five [2%] grade 5 [one treatment related]). 177Lu-PSMA-617 prolonged radiographic progression-free survival relative to ARPI change, with a favourable safety profile. For patients with PSMA-positive metastatic castration-resistant prostate cancer who are being considered for a change of ARPI after progression on a previous ARPI, 177Lu-PSMA-617 may be an effective treatment alternative. Novartis. [ABSTRACT FROM AUTHOR] |
| Copyright of Lancet is the property of Lancet and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
| FullText | Text: Availability: 0 |
|---|---|
| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 179949297 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
| IllustrationInfo | |
| Items | – Name: Title Label: Title Group: Ti Data: 177Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor therapy for taxane-naive patients with progressive metastatic castration-resistant prostate cancer (PSMAfore): a phase 3, randomised, controlled trial. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Morris%2C+Michael+J%22">Morris, Michael J</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Castellano%2C+Daniel%22">Castellano, Daniel</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Herrmann%2C+Ken%22">Herrmann, Ken</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22de+Bono%2C+Johann+S%22">de Bono, Johann S</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Shore%2C+Neal+D%22">Shore, Neal D</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Chi%2C+Kim+N%22">Chi, Kim N</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Crosby%2C+Michael%22">Crosby, Michael</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Piulats%2C+Josep+M%22">Piulats, Josep M</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Fléchon%2C+Aude%22">Fléchon, Aude</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wei%2C+Xiao+X%22">Wei, Xiao X</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Mahammedi%2C+Hakim%22">Mahammedi, Hakim</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Roubaud%2C+Guilhem%22">Roubaud, Guilhem</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Študentová%2C+Hana%22">Študentová, Hana</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Nagarajah%2C+James%22">Nagarajah, James</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Mellado%2C+Begoña%22">Mellado, Begoña</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Montesa-Pino%2C+Álvaro%22">Montesa-Pino, Álvaro</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kpamegan%2C+Euloge%22">Kpamegan, Euloge</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ghebremariam%2C+Samson%22">Ghebremariam, Samson</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kreisl%2C+Teri+N%22">Kreisl, Teri N</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wilke%2C+Celine%22">Wilke, Celine</searchLink> (AUTHOR) – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Lancet%22">Lancet</searchLink>. 9/28/2024, Vol. 404 Issue 10459, p1227-1239. 13p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Prostate-specific+membrane+antigen%22">Prostate-specific membrane antigen</searchLink><br /><searchLink fieldCode="DE" term="%22Castration-resistant+prostate+cancer%22">Castration-resistant prostate cancer</searchLink><br /><searchLink fieldCode="DE" term="%22Androgen+receptors%22">Androgen receptors</searchLink><br /><searchLink fieldCode="DE" term="%22Progression-free+survival%22">Progression-free survival</searchLink><br /><searchLink fieldCode="DE" term="%22Overall+survival%22">Overall survival</searchLink><br /><searchLink fieldCode="DE" term="%22Medical+screening%22">Medical screening</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) prolongs radiographic progression-free survival and overall survival in patients with metastatic castration-resistant prostate cancer previously treated with androgen receptor pathway inhibitor (ARPI) and taxane therapy. We aimed to investigate the efficacy of 177Lu-PSMA-617 in patients with taxane-naive metastatic castration-resistant prostate cancer. In this phase 3, randomised, controlled trial conducted at 74 sites across Europe and North America, taxane-naive patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer who had progressed once on a previous ARPI were randomly allocated (1:1) to open-label, intravenous 177Lu-PSMA-617 at a dosage of 7·4 GBq (200 mCi) ± 10% once every 6 weeks for six cycles, or a change of ARPI (to abiraterone or enzalutamide, administered orally on a continuous basis per product labelling). Crossover from ARPI change to 177Lu-PSMA-617 was allowed after centrally confirmed radiographic progression. The primary endpoint was radiographic progression-free survival, defined as the time from randomisation until radiographic progression or death, assessed in the intention-to-treat population. Safety was a secondary endpoint. This study is registered with ClinicalTrials.gov (NCT04689828) and is ongoing. In this primary report of the study, we present primary (first data cutoff) and updated (third data cutoff) analyses of radiographic progression-free survival; all other data are based on the third data cutoff. Overall, of the 585 patients screened, 468 met all eligibility criteria and were randomly allocated between June 15, 2021 and Oct 7, 2022 to receive 177Lu-PSMA-617 (234 [50%] patients) or ARPI change (234 [50%]). Baseline characteristics were mostly similar between groups; median number of 177Lu-PSMA-617 cycles was 6·0 (IQR 4·0–6·0). Of patients assigned to ARPI change, 134 (57%) crossed over to receive 177Lu-PSMA-617. In the primary analysis (median time from randomisation to first data cutoff 7·26 months [IQR 3·38–10·55]), the median radiographic progression-free survival was 9·30 months (95% CI 6·77–not estimable) in the 177Lu-PSMA-617 group versus 5·55 months (4·04–5·95) in the ARPI change group (hazard ratio [HR] 0·41 [95% CI 0·29–0·56]; p<0·0001). In the updated analysis at time of the third data cutoff (median time from randomisation to third data cutoff 24·11 months [IQR 20·24–27·40]), median radiographic progression-free survival was 11·60 months (95% CI 9·30–14·19) in the 177Lu-PSMA-617 group versus 5·59 months (4·21–5·95) in the ARPI change group (HR 0·49 [95% CI 0·39–0·61]). The incidence of grade 3–5 adverse events was lower in the 177Lu-PSMA-617 group (at least one event in 81 [36%] of 227 patients; four [2%] grade 5 [none treatment related]) than the ARPI change group (112 [48%] of 232; five [2%] grade 5 [one treatment related]). 177Lu-PSMA-617 prolonged radiographic progression-free survival relative to ARPI change, with a favourable safety profile. For patients with PSMA-positive metastatic castration-resistant prostate cancer who are being considered for a change of ARPI after progression on a previous ARPI, 177Lu-PSMA-617 may be an effective treatment alternative. Novartis. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Lancet is the property of Lancet and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
| PLink | https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=179949297 |
| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1016/S0140-6736(24)01653-2 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 13 StartPage: 1227 Subjects: – SubjectFull: Prostate-specific membrane antigen Type: general – SubjectFull: Castration-resistant prostate cancer Type: general – SubjectFull: Androgen receptors Type: general – SubjectFull: Progression-free survival Type: general – SubjectFull: Overall survival Type: general – SubjectFull: Medical screening Type: general Titles: – TitleFull: 177Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor therapy for taxane-naive patients with progressive metastatic castration-resistant prostate cancer (PSMAfore): a phase 3, randomised, controlled trial. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Morris, Michael J – PersonEntity: Name: NameFull: Castellano, Daniel – PersonEntity: Name: NameFull: Herrmann, Ken – PersonEntity: Name: NameFull: de Bono, Johann S – PersonEntity: Name: NameFull: Shore, Neal D – PersonEntity: Name: NameFull: Chi, Kim N – PersonEntity: Name: NameFull: Crosby, Michael – PersonEntity: Name: NameFull: Piulats, Josep M – PersonEntity: Name: NameFull: Fléchon, Aude – PersonEntity: Name: NameFull: Wei, Xiao X – PersonEntity: Name: NameFull: Mahammedi, Hakim – PersonEntity: Name: NameFull: Roubaud, Guilhem – PersonEntity: Name: NameFull: Študentová, Hana – PersonEntity: Name: NameFull: Nagarajah, James – PersonEntity: Name: NameFull: Mellado, Begoña – PersonEntity: Name: NameFull: Montesa-Pino, Álvaro – PersonEntity: Name: NameFull: Kpamegan, Euloge – PersonEntity: Name: NameFull: Ghebremariam, Samson – PersonEntity: Name: NameFull: Kreisl, Teri N – PersonEntity: Name: NameFull: Wilke, Celine IsPartOfRelationships: – BibEntity: Dates: – D: 28 M: 09 Text: 9/28/2024 Type: published Y: 2024 Identifiers: – Type: issn-print Value: 01406736 Numbering: – Type: volume Value: 404 – Type: issue Value: 10459 Titles: – TitleFull: Lancet Type: main |
| ResultId | 1 |
