Rechercher
image du produit
Lancet Oncology, The

S'abonner

Overall survival with [177Lu]Lu-PSMA-617 versus cabazitaxel in metastatic castration-resistant prostate cancer (TheraP): secondary outcomes of a randomised, open-label, phase 2 trial - 03/01/24

Doi : 10.1016/S1470-2045(23)00529-6 
Michael S Hofman, ProfMBBS a, b, ⁎ , Louise Emmett, ProfMD d, f, Shahneen Sandhu, MBBS a, b, Amir Iravani, MD a, James P Buteau, MD a, b, Anthony M Joshua, ProfPhD e, Jeffrey C Goh, ProfMBBS g, aj, David A Pattison, MBBS h, i, Thean Hsiang Tan, MBBS k, ak, Ian D Kirkwood, MBBS l, ak, Siobhan Ng, MBBS m, o, Roslyn J Francis, PhD n, o, Craig Gedye, PhD p, q, Natalie K Rutherford, MD q, r, Andrew Weickhardt, PhD s, u, Andrew M Scott, ProfMD c, t, u, v, Sze-Ting Lee, PhD c, t, u, v, Edmond M Kwan, PhD w, Arun A Azad, PhD a, b, Shakher Ramdave, MD x, Andrew D Redfern, MBChB o, y, William Macdonald, MPH o, y, z, Alex Guminski, PhD aa, Edward Hsiao, MBChB ab, Wei Chua, PhD ac, Peter Lin, MBBS f, ad, Alison Yan Zhang, PhD ae, af, ag, Martin R Stockler, ProfMBBS ae, ag, Scott G Williams, ProfMD a, b, Andrew J Martin, ProfPhD j, ae, Ian D Davis, ProfPhD ah, ai
for the

TheraP Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group†

  All TheraP trial collaborators are listed in the Supplementary Material)
Tim Akhurst, Ramin Alipour, Dale Bailey, Patricia Banks, Alexis Beaulieu, Louise Campbell, Megan Crumbaker, Nattakorn Dhiantravan, Anis Hamid, Mohammad Haskali, Terry Hung, Grace Kong, Nick Lawrence, Jeremy Lewin, Michael McCarthy, Kate Moodie, Declan Murphy, Andrew Nguyen, David Pook, Aravind Ravi Kumar, Paul Roach, Peter Roselt, Javad Saghebi, Geoff Schembri, Lavinia Spain, Shalini Subramaniam, Sue Ping Thang, Paul Thomas, Ben Tran, Roslyn Wallace, Sonia Yip

a Prostate Theranostics and Imaging Centre of Excellence, Molecular Imaging and Therapeutic Nuclear Medicine, Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia 
b Sir Peter MacCallum Department of Oncology, Faculty of Medicine, The University of Melbourne, Melbourne, VIC, Australia 
c Department of Medicine, Faculty of Medicine, The University of Melbourne, Melbourne, VIC, Australia 
d Department of Theranostics and Nuclear Medicine, St Vincent’s Hospital, Sydney, NSW, Australia 
e Department of Medical Oncology, Kinghorn Cancer Centre, St Vincent’s Hospital, Sydney, NSW, Australia 
f Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia 
g Medical Oncology, Royal Brisbane and Women’s Hospital, Brisbane, QLD, Australia 
h Department of Nuclear Medicine and Specialised PET Services, Royal Brisbane and Women’s Hospital, Brisbane, QLD, Australia 
i School of Medicine, University of Queensland, Brisbane, QLD, Australia 
j Centre for Clinical Research, University of Queensland, Brisbane, QLD, Australia 
k Department of Medical Oncology, Royal Adelaide Hospital, Adelaide, SA, Australia 
l Department of Nuclear Medicine and PET, Royal Adelaide Hospital, Adelaide, SA, Australia 
m Department of Oncology, Sir Charles Gairdner Hospital, Perth, WA, Australia 
n Department of Nuclear Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia 
o Medical School, University of Western Australia, Perth, WA, Australia 
p Department of Medical Oncology, Calvary Mater Newcastle, Waratah, NSW, Australia 
q School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia 
r Department of Nuclear Medicine, Hunter New England Health, New Lambton, NSW, Australia 
s Olivia Newton-John Cancer and Wellness Centre, Austin Health, Melbourne, VIC, Australia 
t Department of Molecular Imaging and Therapy, Austin Health, Melbourne, VIC, Australia 
u School of Cancer Medicine, La Trobe University, Melbourne, VIC, Australia 
v Olivia Newton-John Cancer Research Institute, Melbourne, VIC, Australia 
w Department of Medical Oncology, Monash Health, Melbourne, VIC, Australia 
x Monash Health Imaging, Monash Health, Melbourne, VIC, Australia 
y Department of Medical Oncology, Fiona Stanley Hospital, Perth, WA, Australia 
z Department of Nuclear Medicine, Fiona Stanley Hospital, Perth, WA, Australia 
aa Department of Medical Oncology, Royal North Shore Hospital, University of Sydney, Sydney, NSW, Australia 
ab Department of Nuclear Medicine and PET, Royal North Shore Hospital, University of Sydney, Sydney, NSW, Australia 
ac Department of Medical Oncology, Liverpool Hospital, Sydney, NSW, Australia 
ad Department of Nuclear Medicine and PET, Liverpool Hospital, Sydney, NSW, Australia 
ae NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia 
af Department of Medical Oncology, Macquarie University Hospital, Sydney, NSW, Australia 
ag Department of Medical Oncology, Chris O’Brien Lifehouse, Sydney, NSW, Australia 
ah Monash University Eastern Health Clinical School, Melbourne, VIC, Australia 
ai Eastern Health Department of Cancer Services, Eastern Health, Melbourne, VIC, Australia 
aj Queensland University of Technology, Brisbane, QLD, Australia 
ak Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA, Australia 

*Correspondence to: Prof Michael S Hofman, Prostate Theranostics and Imaging Centre of Excellence, Molecular Imaging and Therapeutic Nuclear Medicine, Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, AustraliaProstate Theranostics and Imaging Centre of ExcellenceMolecular Imaging and Therapeutic Nuclear MedicineCancer ImagingPeter MacCallum Cancer CentreMelbourneVIC3000Australia

Summary

Background

The TheraP study reported improved prostate-specific antigen responses with lutetium-177 [177Lu]Lu-PSMA-617 versus cabazitaxel in men with metastatic castration-resistant prostate cancer progressing after docetaxel. In this Article, we report the secondary outcome of overall survival with mature follow-up, and an updated imaging biomarker analysis. We also report the outcomes of participants excluded due to ineligibility on gallium-68 [68Ga]Ga-PSMA-11 and 2-[18F]fluoro-2-deoxy-D-glucose (2-[18F]FDG) PET-CT.

Methods

TheraP was an open-label, randomised phase 2 trial at 11 centres in Australia. Eligible participants had metastatic castration-resistant prostate cancer progressing after docetaxel, and PET imaging with [68Ga]Ga-PSMA-11 and 2-[18F]FDG that showed prostate-specific membrane antigen (PSMA)-positive disease and no sites of metastatic disease with discordant 2-[18F]FDG-positive and PSMA-negative findings. Participants were randomly assigned (1:1) to treatment with [177Lu]Lu-PSMA-617 (every 6 weeks for a maximum of six cycles; starting at 8·5 GBq, decreasing by 0.5 GBq to 6·0 GBq for the sixth cycle) versus cabazitaxel (20 mg/m2 every 3 weeks, maximum of ten cycles). Overall survival was analysed by intention-to-treat and summarised as restricted mean survival time (RMST) to account for non-proportional hazards, with a 36-month restriction time corresponding to median follow-up. This trial is registered with ClinicalTrials.gov, NCT03392428, and is complete.

Findings

291 men were registered from Feb 6, 2018, to Sept 3, 2019; after study imaging, 200 were eligible and randomly assigned to treatment with [177Lu]Lu-PSMA-617 (n=99) or cabazitaxel (n=101). After completing study treatment, 20 (20%) participants assigned to cabazitaxel and 32 (32%) assigned to [177Lu]Lu-PSMA-617 were subsequently treated with the alternative regimen. After a median follow-up of 35·7 months (IQR 31·1 to 39·2), 77 (78%) participants had died in the [177Lu]Lu-PSMA-617 group and 70 (69%) participants had died in the cabazitaxel group. Overall survival was similar among those assigned to [177Lu]Lu-PSMA-617 versus those assigned to cabazitaxel (RMST 19·1 months [95% CI 16·9 to 21·4] vs 19·6 months [17·4 to 21·8]; difference –0·5 months [95% CI –3·7 to 2·7]; p=0·77). No additional safety signals were identified with the longer follow-up in this analysis. 80 (27%) of 291 men who were registered after initial eligibility screening were excluded after [68Ga]Ga-PSMA-11 and 2-[18F]FDG PET. In the 61 of these men with follow-up available, RMST was 11·0 months (95% CI 9·0 to 13·1).

Interpretation

These results support the use of [177Lu]Lu-PSMA-617 as an alternative to cabazitaxel for PSMA-positive metastatic castration-resistant prostate cancer progressing after docetaxel. We did not find evidence that overall survival differed between the randomised groups. Median overall survival was shorter for men who were excluded because of low PSMA expression or 2-[18F]FDG-discordant disease.

Funding

Australian and New Zealand Urogenital and Prostate Cancer Trials Group, Prostate Cancer Foundation of Australia, Endocyte (a Novartis company), Australian Nuclear Science and Technology Organization, Movember, It’s a Bloke Thing, CAN4CANCER, and The Distinguished Gentleman’s Ride.

Le texte complet de cet article est disponible en PDF.

Plan


© 2024  Elsevier Ltd. Tous droits réservés.
Ajouter à ma bibliothèque Retirer de ma bibliothèque Imprimer
Export

    Export citations

  • Fichier

    •

  • Contenu

    •

Vol 25 - N° 1

P. 99-107 - janvier 2024 Retour au numéro
Article précédent Article précédent
  • Mortality from leading cancers in districts of England from 2002 to 2019: a population-based, spatiotemporal study
  • Theo Rashid, James E Bennett, David C Muller, Amanda J Cross, Jonathan Pearson-Stuttard, Perviz Asaria, Hima Iyathooray Daby, Daniela Fecht, Bethan Davies, Majid Ezzati
| Article suivant Article suivant
  • Effect of baseline oestradiol serum concentration on the efficacy of anastrozole for preventing breast cancer in postmenopausal women at high risk: a case-control study of the IBIS-II prevention trial
  • Jack Cuzick, Kim Chu, Brian Keevil, Adam R Brentnall, Anthony Howell, Nicholas Zdenkowski, Bernardo Bonanni, Sibylle Loibl, Kaija Holli, D Gareth Evans, Steve Cummings, Mitch Dowsett

Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.

Déjà abonné à cette revue ?

Elsevier s'engage à rendre ses eBooks accessibles et à se conformer aux lois applicables. Compte tenu de notre vaste bibliothèque de titres, il existe des cas où rendre un livre électronique entièrement accessible présente des défis uniques et l'inclusion de fonctionnalités complètes pourrait transformer sa nature au point de ne plus servir son objectif principal ou d'entraîner un fardeau disproportionné pour l'éditeur. Par conséquent, l'accessibilité de cet eBook peut être limitée. Voir plus

Accès rapides

Mon compte

Aide & support

Plateformes Elsevier Masson

Déclaration CNIL

EM-CONSULTE.COM est déclaré à la CNIL, déclaration n° 1286925.

En application de la loi nº78-17 du 6 janvier 1978 relative à l'informatique, aux fichiers et aux libertés, vous disposez des droits d'opposition (art.26 de la loi), d'accès (art.34 à 38 de la loi), et de rectification (art.36 de la loi) des données vous concernant. Ainsi, vous pouvez exiger que soient rectifiées, complétées, clarifiées, mises à jour ou effacées les informations vous concernant qui sont inexactes, incomplètes, équivoques, périmées ou dont la collecte ou l'utilisation ou la conservation est interdite.
Les informations personnelles concernant les visiteurs de notre site, y compris leur identité, sont confidentielles.
Le responsable du site s'engage sur l'honneur à respecter les conditions légales de confidentialité applicables en France et à ne pas divulguer ces informations à des tiers.

Tout le contenu de ce site: Copyright © 2026 Elsevier, ses concédants de licence et ses contributeurs. Tout les droits sont réservés, y compris ceux relatifs à l'exploration de textes et de données, a la formation en IA et aux technologies similaires. Pour tout contenu en libre accès, les conditions de licence Creative Commons s'appliquent.