Evidence map›Paper›PMID 32205016›Full record

ArticleAnnals of oncology : official journal of the European Society for Medical Oncology2020

A phase I dose-escalation study of enzalutamide in combination with the AKT inhibitor AZD5363 (capivasertib) in patients with metastatic castration-resistant prostate cancer.

M P Kolinsky, P Rescigno, D Bianchini, Z Zafeiriou, N Mehra, J Mateo, V Michalarea, R Riisnaes, M Crespo, I Figueiredo and 20 more

Registry-linked trialOpen access · bronzeAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Annals of oncology : official journal of the European Society for Medical Oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02525068 (A Randomised Phase II Study of Enzalutamide), which is not on this map. Cited by 51 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 1 pooled it
6.8field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02525068 phase2unknown statusnot on this map

A Randomised Phase II Study of Enzalutamide (MDV3100) in Combination With AZD5363 in Patients With Metastatic Castration-Resistant Prostate Cancer (RE-AKT)

TypeinterventionalSponsorInstitute of Cancer Research, United KingdomRan2014 to 2020Enrolled136ConditionsAdenocarcinoma of the ProstateArmsAZD5363, Enzalutamide
3 · Its place in the literature

Who cites it

51 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.

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  4. Phase Ib/II Study of Enzalutamide with Samotolisib (LY3023414) or Placebo in Patients with Metastatic Castration-Resistant Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

30 authors at 4 institutions in 3 countries.

M P KolinskyThe Royal Marsden NHS Foundation Trust, London, UK; The Institute of Cancer Research, London, UK; Cross Cancer Institute, Edmonton, Canada.
P RescignoThe Royal Marsden NHS Foundation Trust, London, UK; The Institute of Cancer Research, London, UK; Department of Clinical Medicine and Surgery, Department of Translational Medical Sciences, AOU Federico II, Naples, Italy.
D BianchiniThe Royal Marsden NHS Foundation Trust, London, UK; The Institute of Cancer Research, London, UK.
Z ZafeiriouThe Royal Marsden NHS Foundation Trust, London, UK; The Institute of Cancer Research, London, UK.
N MehraThe Royal Marsden NHS Foundation Trust, London, UK; The Institute of Cancer Research, London, UK.
J MateoThe Royal Marsden NHS Foundation Trust, London, UK; The Institute of Cancer Research, London, UK.
V MichalareaThe Royal Marsden NHS Foundation Trust, London, UK; The Institute of Cancer Research, London, UK.
R RiisnaesThe Institute of Cancer Research, London, UK.
M CrespoThe Institute of Cancer Research, London, UK.
I FigueiredoThe Institute of Cancer Research, London, UK.
S MirandaThe Institute of Cancer Research, London, UK.
D Nava RodriguesThe Institute of Cancer Research, London, UK.
P FlohrThe Institute of Cancer Research, London, UK.
N TunariuThe Royal Marsden NHS Foundation Trust, London, UK; The Institute of Cancer Research, London, UK.
U BanerjiThe Royal Marsden NHS Foundation Trust, London, UK; The Institute of Cancer Research, London, UK.
R RuddleThe Institute of Cancer Research, London, UK.
A SharpThe Royal Marsden NHS Foundation Trust, London, UK; The Institute of Cancer Research, London, UK.
J WeltiThe Institute of Cancer Research, London, UK.
M LambrosThe Institute of Cancer Research, London, UK.
S CarreiraThe Institute of Cancer Research, London, UK.
F I RaynaudThe Institute of Cancer Research, London, UK.
K E SwalesThe Institute of Cancer Research, London, UK.
S PlymateUniversity of Washington School of Medicine, Seattle, USA.
J LuoBrady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, USA.
H ToveyThe Institute of Cancer Research, London, UK.
N PortaThe Institute of Cancer Research, London, UK.
R SladeThe Institute of Cancer Research, London, UK.
L LeonardThe Institute of Cancer Research, London, UK.
E HallThe Institute of Cancer Research, London, UK.
J S de BonoThe Royal Marsden NHS Foundation Trust, London, UK; The Institute of Cancer Research, London, UK. Electronic address: johann.de-bono@icr.ac.uk.
Institute of Cancer Research · GBRoyal Marsden NHS Foundation Trust · GBJohns Hopkins University · USUniversity of Washington · US

Funding

Cancer Research UK 25351Cancer Research UK CRUKE/12/050Medical Research Council MR/M018318/1
6 · The paper itself

Abstract

backgroundActivation of the PI3K/AKT/mTOR pathway through loss of phosphatase and tensin homolog (PTEN) occurs in approximately 50% of patients with metastatic castration-resistant prostate cancer (mCRPC). Recent evidence suggests that combined inhibition of the androgen receptor (AR) and AKT may be beneficial in mCRPC with PTEN loss. PATIENTS AND

methodsmCRPC patients who previously failed abiraterone and/or enzalutamide, received escalating doses of AZD5363 (capivasertib) starting at 320 mg twice daily (b.i.d.) given 4 days on and 3 days off, in combination with enzalutamide 160 mg daily. The co-primary endpoints were safety/tolerability and determining the maximum tolerated dose and recommended phase II dose; pharmacokinetics, antitumour activity, and exploratory biomarker analysis were also evaluated.

resultsSixteen patients were enrolled, 15 received study treatment and 13 were assessable for dose-limiting toxicities (DLTs). Patients were treated at 320, 400, and 480 mg b.i.d. dose levels of capivasertib. The recommended phase II dose identified for capivasertib was 400 mg b.i.d. with 1/6 patients experiencing a DLT (maculopapular rash) at this level. The most common grade ≥3 adverse events were hyperglycemia (26.7%) and rash (20%). Concomitant administration of enzalutamide significantly decreased plasma exposure of capivasertib, though this did not appear to impact pharmacodynamics. Three patients met the criteria for response (defined as prostate-specific antigen decline ≥50%, circulating tumour cell conversion, and/or radiological response). Responses were seen in patients with PTEN loss or activating mutations in AKT, low or absent AR-V7 expression, as well as those with an increase in phosphorylated extracellular signal-regulated kinase (pERK) in post-exposure samples.

conclusionsThe combination of capivasertib and enzalutamide is tolerable and has antitumour activity, with all responding patients harbouring aberrations in the PI3K/AKT/mTOR pathway. CLINICAL TRIAL NUMBER: NCT02525068.

Indexed as

Prostatic Neoplasms, Castration-ResistantAntineoplastic Combined Chemotherapy ProtocolsBenzamidesHumansMaleNitrilesPhenylthiohydantoinPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktPyrimidinesPyrrolesTreatment OutcomeBenzamidescapivasertibenzalutamideNitrilesPhenylthiohydantoinPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktPyrimidinesPyrrolesAKT inhibitorAZD5363biomarkerscapivasertibenzalutamideprostate cancer

Identifiers

PMID32205016
PMCPMC7217345
OpenAlexW3007796943

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.