177Lu-PSMA-617 and Idronoxil in Men with End-Stage Metastatic Castration-Resistant Prostate Cancer (LuPIN): Patient Outcomes and Predictors of Treatment Response in a Phase I/II Trial
Rattachement africain : au, nz. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Background:177Lutetium PSMA-617 (Lu-PSMA-617) is an effective therapy for metastatic castrate-resistant prostate cancer (mCRPC). However, treatment resistance occurs frequently and combination therapies may improve outcomes. We report the final safety and efficacy results of a phase I/II study combining Lu-PSMA-617 with idronoxil (NOX66), a radiosensitiser, and examined potential clinical, blood-based and imaging biomarkers. Methods: 56 men with progressive mCRPC previously treated with taxane chemotherapy and novel androgen signaling inhibitor (ASI) were enrolled. Patients received up to six doses of Lu-PSMA-617 (7.5Gbq) day 1 in combination with NOX66 suppository days 1-10 each 6-week cycle. Cohort 1 (n = 8) received 400mg NOX66, cohort 2 (n = 24) received 800mg and cohort 3 (n = 24) received 1200mg. 68Ga-PSMA and FDG PET/CT were performed at study entry and semi-quantitative imaging analysis was undertaken. Blood samples were collected for blood-based biomarkers including androgen receptor splice variant 7 expression. The primary outcomes were safety and tolerability; secondary outcomes included efficacy, pain scores and xerostomia. Regression analyses were performed to explore the prognostic value of baseline clinical, blood-based and imaging parameters. Results: 56/100 men screened were enrolled (56%) with a screen failure rate of 26% (26/100) for PET imaging criteria. All men had received prior treatment with ASI and docetaxel, and 95% (53/56) had received cabazitaxel. 96% (54/56) patients received ≥2 cycles of combination NOX66 and Lu-PSMA-617, and 46% (26/56) completed six cycles. Common adverse events were anaemia, fatigue and xerostomia. Anal irritation attributable to NOX66 occurred in 38%. 48/56 had a reduction in prostate-specific antigen (PSA) (86%, 95% CI 74-94), 34/56 (61%, 95% CI 47-74) had a PSA reduction ≥50% (PSA50). Median PSA progression-free survival was 7.5 months (95% CI 5.9-9) and median overall survival 19.7 months (95% CI 9.5-30). Higher PSMA SUVmean correlated with treatment response, while higher PSMA tumour volume and prior treatment with ASI for less than 12 months were associated with worse overall survival. Conclusion: NOX66 with Lu-PSMA-617 is a safe and feasible therapeutic strategy in men treated 3rd line and beyond for mCRPC. PSMA SUVmean, PSMA avid tumour volume and duration of treatment with ASI were independently associated with outcome.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.
- Titre Crossref
- <sup>177</sup>Lu-PSMA-617 and Idronoxil in Men with End-Stage Metastatic Castration-Resistant Prostate Cancer (LuPIN): Patient Outcomes and Predictors of Treatment Response in a Phase I/II Trial
- Date Crossref
- 29/07/2021
- Éditeur
- Society of Nuclear Medicine
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
-
Garvan Institute of Medical Research pays non établi dans la noticeOrganisation à but non lucratif
-
St Vincent's Hospital Melbourne Department of Theranostics and Nuclear Medicine pays non établi dans la noticeÉtablissement de santé
-
St Vincent's Hospital Sydney Department of Theranostics and Nuclear Medicine pays non établi dans la noticeÉtablissement de santé
-
The Kinghorn Cancer Centre pays non établi dans la noticeÉtablissement de santé
-
UNSW Sydney pays non établi dans la noticeUniversité ou école supérieure
-
St Vincent's Clinic pays non établi dans la noticeÉtablissement de santé
-
Prince of Wales Hospital Nelune Comprehensive Cancer Centre pays non établi dans la noticeÉtablissement de santé
-
Hunter Medical Research Institute pays non établi dans la noticeStructure de recherche
-
Calvary Mater Newcastle Hospital pays non établi dans la noticeÉtablissement de santé
-
Monash Health pays non établi dans la noticeÉtablissement de santé
-
Monash University pays non établi dans la noticeUniversité ou école supérieure
-
Peter MacCallum Cancer Centre pays non établi dans la noticeÉtablissement de santé
Garvan Institute of Medical Research, Department of Theranostics and Nuclear Medicine — St Vincent's Hospital Melbourne et Department of Theranostics and Nuclear Medicine — St Vincent's Hospital Sydney, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.