dc.contributor.author | Rescigno, P | |
dc.contributor.author | Porta, N | |
dc.contributor.author | Finneran, L | |
dc.contributor.author | Riisnaes, R | |
dc.contributor.author | Figueiredo, I | |
dc.contributor.author | Carreira, S | |
dc.contributor.author | Flohr, P | |
dc.contributor.author | Miranda, S | |
dc.contributor.author | Bertan, C | |
dc.contributor.author | Ferreira, A | |
dc.contributor.author | Crespo, M | |
dc.contributor.author | Rodrigues, DN | |
dc.contributor.author | Gurel, B | |
dc.contributor.author | Nobes, J | |
dc.contributor.author | Crabb, S | |
dc.contributor.author | Malik, Z | |
dc.contributor.author | Ralph, C | |
dc.contributor.author | McGovern, U | |
dc.contributor.author | Hoskin, P | |
dc.contributor.author | Jones, RJ | |
dc.contributor.author | Birtle, A | |
dc.contributor.author | Gale, J | |
dc.contributor.author | Sankey, P | |
dc.contributor.author | Jain, S | |
dc.contributor.author | McLaren, D | |
dc.contributor.author | Chadwick, E | |
dc.contributor.author | Espinasse, A | |
dc.contributor.author | Hall, E | |
dc.contributor.author | de Bono, J | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2024-08-09T11:02:58Z | |
dc.date.available | 2024-08-09T11:02:58Z | |
dc.date.issued | 2024-07-01 | |
dc.identifier | ARTN 114103 | |
dc.identifier | S0959-8049(24)00759-7 | |
dc.identifier.citation | European Journal of Cancer, 2024, 205 pp. 114103 - | en_US |
dc.identifier.issn | 0959-8049 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/6343 | |
dc.identifier.eissn | 1879-0852 | |
dc.identifier.eissn | 1879-0852 | |
dc.identifier.doi | 10.1016/j.ejca.2024.114103 | |
dc.identifier.doi | 10.1016/j.ejca.2024.114103 | |
dc.description.abstract | BACKGROUND: PTEN loss and aberrations in PI3K/AKT signaling kinases associate with poorer response to abiraterone acetate (AA) in metastatic castration-resistant prostate cancer (mCRPC). In this study, we assessed antitumor activity of the AKT inhibitor capivasertib combined with enzalutamide in mCRPC with prior progression on AA and docetaxel. METHODS: This double-blind, placebo-controlled, randomized phase 2 trial, recruited men ≥ 18 years with progressing mCRPC and performance status 0-2 from 15 UK centers. Randomized participants (1:1) received enzalutamide (160 mg orally, once daily) with capivasertib (400 mg)/ placebo orally, twice daily on an intermittent (4 days on, 3 days off) schedule. Primary endpoint was composite response rate (RR): RECIST 1.1 objective response, ≥ 50 % PSA decrease from baseline, or circulating tumor cell count conversion (from ≥ 5 at baseline to < 5 cells/7.5 mL). Subgroup analyses by PTENIHC status were pre-planned. RESULTS: Overall, 100 participants were randomized (50:50); 95 were evaluable for primary endpoint (47:48); median follow-up was 43 months. RR were 9/47 (19.1 %) enzalutamide/capivasertib and 9/48 (18.8 %) enzalutamide/placebo (absolute difference 0.4 % 90 %CI -12.8 to 13.6, p = 0.58), with similar results in the PTENIHC loss subgroup. Irrespective of treatment, OS was significantly worse for PTENIHC loss (10.1 months [95 %CI: 4.6-13.9] vs 14.8 months [95 %CI: 10.8-18]; p = 0.02). Most common treatment-emergent grade ≥ 3 adverse events for the combination were diarrhea (13 % vs 2 %) and fatigue (10 % vs 6 %). CONCLUSIONS: Combined capivasertib/enzalutamide was well tolerated but didn't significantly improve outcomes from abiraterone pre-treated mCRPC. | |
dc.format | Print-Electronic | |
dc.format.extent | 114103 - | |
dc.language | eng | |
dc.language.iso | eng | en_US |
dc.publisher | ELSEVIER SCI LTD | en_US |
dc.relation.ispartof | European Journal of Cancer | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc/4.0 | en_US |
dc.subject | AKT-inhibitor | |
dc.subject | Enzalutamide | |
dc.subject | PTEN | |
dc.subject | Phase II randomized trial | |
dc.subject | Prostate cancer | |
dc.subject | Humans | |
dc.subject | Male | |
dc.subject | Prostatic Neoplasms, Castration-Resistant | |
dc.subject | Phenylthiohydantoin | |
dc.subject | Benzamides | |
dc.subject | Docetaxel | |
dc.subject | Aged | |
dc.subject | Antineoplastic Combined Chemotherapy Protocols | |
dc.subject | Middle Aged | |
dc.subject | Nitriles | |
dc.subject | Double-Blind Method | |
dc.subject | Pyrimidines | |
dc.subject | Androstenes | |
dc.subject | Aged, 80 and over | |
dc.subject | Pyrroles | |
dc.title | Capivasertib in combination with enzalutamide for metastatic castration resistant prostate cancer after docetaxel and abiraterone: Results from the randomized phase II RE-AKT trial. | en_US |
dc.type | Journal Article | |
dcterms.dateAccepted | 2024-04-28 | |
dc.date.updated | 2024-08-08T09:31:12Z | |
rioxxterms.version | AM | en_US |
rioxxterms.versionofrecord | 10.1016/j.ejca.2024.114103 | en_US |
rioxxterms.licenseref.startdate | 2024-07-01 | |
rioxxterms.type | Journal Article/Review | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/38729054 | |
pubs.organisational-group | ICR | |
pubs.organisational-group | ICR/Primary Group | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Biomarkers | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Clinical Studies/Cancer Biomarkers | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Trials & Statistics Unit | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group | |
pubs.publication-status | Published | |
pubs.publisher-url | http://dx.doi.org/10.1016/j.ejca.2024.114103 | |
pubs.volume | 205 | |
icr.researchteam | Clin Trials & Stats Unit | en_US |
icr.researchteam | Cancer Biomarkers | en_US |
icr.researchteam | PrCa Targeted Therapy | en_US |
dc.contributor.icrauthor | Porta, Nuria | |
dc.contributor.icrauthor | Finneran, Laura | |
dc.contributor.icrauthor | Carreira, Suzanne | |
dc.contributor.icrauthor | Crespo, Mateus | |
dc.contributor.icrauthor | Hall, Emma | |
dc.contributor.icrauthor | De Bono, Johann | |
icr.provenance | Deposited by Ms Jessica Phelps (impersonating Prof Emma Hall) on 2024-08-08. Deposit type is initial. No. of files: 3. Files: Supplementary Appendix v1.1_clean.pdf; Highlights v1.1_clean.pdf; REAKT_phase2_Manuscript v1.1_clean.pdf | |