KEYNOTE-641: A Phase III Study of Pembrolizumab Plus Enzalutamide for Metastatic Castration-Resistant Prostate Cancer

Graff, Julie N.; Liang, Li; Kim, Jeri; Stenzl, Arnulf

doi:10.2217/fon-2020-1008

Cited by 31 publications

(13 citation statements)

References 48 publications

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“…For example, in the phase II clinical trial KEYNOTE-199 ( 24 ), pembrolizumab monotherapy was compared with placebo treatment in 258 metastatic CRPC (mCRPC) patients, with response rates of only 5% and 3% in PD-L1-positive and PD-L1-negative cohorts, respectively. In the subsequent phase III clinical trial KEYNOTE-641 ( 25 ), pembrolizumab did not show improvement in PFS or OS compared to the placebo group. The phase II clinical trial CheckMate 650 investigated the combined treatment effect of ipilimumab and nivolumab, with the combination producing only a 25% objective response rate, and the study was stopped in the population due to disease progression and increased side effects.…”

Section: Discussionmentioning

confidence: 94%

Subtype and prognostic analysis of immunogenic cell death-related gene signature in prostate cancer

et al. 2023

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BackgroundImmunogenic cell death (ICD) plays a vital role in tumor progression and immune response. However, the integrative role of ICD-related genes and subtypes in the tumor microenvironment (TME) in prostate cancer (PCa) remains unknown.Materials and methodsThe sample data were obtained from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Memorial Sloan Kettering Cancer Center (MSKCC) prostate cancer-related databases. We first divided the subtypes based on ICD genes from 901 PCa patients and then identified the prognosis- related genes (PRGs) between different ICD subtypes. Subsequently, all the patients were randomly split into the training and test groups. We developed a risk signature in the training set by least absolute shrinkage and selection operator (LASSO)–Cox regression. Following this, we verified this prognostic signature in both the training test and external test sets. The relationships between the different subgroups and clinical pathological characteristics, immune infiltration characteristics, and mutation status of the TME were examined. Finally, the artificial neural network (ANN) and fundamental experiment study were constructed to verify the accuracy of the prognostic signature.ResultsWe identified two ICD clusters with immunological features and three gene clusters composed of PRGs. Additionally, we demonstrated that the risk signature can be used to evaluate tumor immune cell infiltration, prognostic status, and an immune checkpoint inhibitor. The low-risk group, which has a high overlap with group C of the gene cluster, is characterized by high ICD levels, immunocompetence, and favorable survival probability. Furthermore, the tumor progression genes selected by the ANN also exhibit potential associations with risk signature genes.ConclusionThis study identified individuals with high ICD levels in prostate cancer who may have more abundant immune infiltration and revealed the potential effects of risk signature on the TME, immune checkpoint inhibitor, and prognosis of PCa.

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Section: Discussionmentioning

confidence: 94%

Subtype and prognostic analysis of immunogenic cell death-related gene signature in prostate cancer

et al. 2023

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“… 136 A phase III KEYNOTE-641 study (ClinicalTrials.gov: NCT03834493 ) is being conducted, and its final results may help us to evaluate the efficacy of pembrolizumab plus enzalutamide as a treatment for mCRPC. 137 Apart from pembrolizumab, ipilimumab was simultaneously assessed in prostate cancer. In two phase III trials including patients with mCRPC who were pretreated with docetaxel or chemotherapy-naive, the median OS in the ipilimumab group did not differ significantly from that in the placebo group.…”

Section: Immunotherapymentioning

confidence: 99%

New insights and options into the mechanisms and effects of combined targeted therapy and immunotherapy in prostate cancer

Lin¹,

Sun²

2023

Molecular Therapy - Oncolytics

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“…KEYNOTE-641 ist eine multizentrische, randomisierte, doppelblinde Phase-III-Studie, in der die Wirksamkeit und Sicherheit von Enzalutamid plus Pembrolizumab+ im Vergleich zu Enzalutamid plus Placebo bei etwa 1200 Patienten mit mCRPC untersucht wird (NCT03834493). Primäre Endpunkte dieser Studie sind das OS und das radiologische PFS (rPFS), die Veröffentlich der Ergebnisse steht noch aus [160].…”

Section: Impfstoffbasierte Immuntherapieunclassified

Stand der Forschung und neue therapeutische Perspektiven in der Immuntherapie des Prostatakarzinoms

Maselli¹,

Giuliani²,

Laface³

et al. 2023

Kompass Onkol

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Das Prostatakarzinom ist die häufigste Art von Tumor bei Männern. Im Frühstadium der Erkrankung ist es empfindlich gegenüber einer Androgenentzugstherapie. Bei Patienten mit metastasiertem kastrationssensitivem Prostatakarzinom (mHSPC) haben Chemotherapie und Androgenrezeptortherapien der zweiten Generation zu einer Verlängerung der Überlebenszeit geführt. Trotz der Fortschritte bei der Behandlung des mHSPC ist eine Kastrationsresistenz unvermeidlich, und viele Patienten entwickeln eine metastasierende kastrationsresistente Erkrankung (mCRPC). In den letzten Jahrzehnten hat die Immuntherapie die onkologische Landschaft dramatisch verändert und die Überlebensraten bei vielen Krebsarten erhöht. Allerdings hat die Immuntherapie beim Prostatakarzinom noch nicht die bahnbrechenden Ergebnisse gebracht, die sie bei anderen Tumorarten erzielt hat. Die Erforschung neuer Behandlungsmöglichkeiten ist für Patienten mit mCRPC aufgrund der schlechten Prognose sehr wichtig. In dieser Übersichtsarbeit konzentrieren wir uns auf die Gründe für die scheinbare intrinsische Resistenz des Prostatakarzinoms gegenüber der Immuntherapie, die Möglichkeiten zur Überwindung dieser Resistenz sowie die klinische Evidenz und auf neue therapeutische Perspektiven für die Immuntherapie des Prostatakarzinoms mit einem Blick in die Zukunft.

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KEYNOTE-641: A Phase III Study of Pembrolizumab Plus Enzalutamide for Metastatic Castration-Resistant Prostate Cancer

Cited by 31 publications

References 48 publications

Subtype and prognostic analysis of immunogenic cell death-related gene signature in prostate cancer

Subtype and prognostic analysis of immunogenic cell death-related gene signature in prostate cancer

New insights and options into the mechanisms and effects of combined targeted therapy and immunotherapy in prostate cancer

Stand der Forschung und neue therapeutische Perspektiven in der Immuntherapie des Prostatakarzinoms

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