30 oktober 2017: Bron: European Urology: August 2015 Volume 68, Issue 2, Pages 267–279

Bij nagenoeg alle vormen van kanker lijkt immuuntherapie de sleutel tot langdurige overleving. Bijna elke week wordt wel ergens een studie gepubliceerd, meestal met anti-PD medicijnen / check pointremmers maar ook andere vormen van immuuntherapie met targeted medicine,, medicijnen die zich richten op 1 of enkele mutaties of ook vormen van dendritische celtherapie met aanvullende immuunstimulerende middelen waaronder gemoduleerde virussen. Ik probeer dit bij te houden maar is onmogelijk door de veelheid alle belangrijke studies ook te publiceren met commentaar. 

Omdat ik naast de website bijhouden ook nog enkele patiënten begeleid kwam ik op deze studie: A Systematic Review of Immunotherapy in Urologic Cancer: Evolving Roles for Targeting of CTLA-4, PD-1/PD-L1, and HLA-G Inline Image eulogo1

die opgemaakt eind 2014 en gepubliceerd in 2015 een overzicht geeft van immuuntherape bij urologische vormen van kanker, zoals blaaskanker,prostaatkanker en nierkanker. 

De studie is dus al weer 2 jaar oud en er zijn al weer veel aanvullingen te maken, maar voor de meeste studies moet betaald worden voor een volledig studierapport. En deze studie geeft wel een goed overzicht van hoe immuuntherapie precies werkt, welke bepaalde mutaties een rol daarbij spelen en welke ontwikkelingen er plaatsvinden bij urologische vormen van kanker. En is uitgeplitst in de verschillende vormen van immuuntherapie en beschrijft het tot nu toe gedaan onderzoek bij respectievelijk blaaskanker, prostaatkanker en nierkanker.

immuuntherapie bij urologische vormen van kanker

Hier enkele citatn uit de conclusie van deze reviewstudie:

An improved understanding of the molecular mechanisms that govern interactions between a tumor and the host immune response has led to major advances in targeted immunotherapy and cancer treatments. Our systematic review demonstrates that immune checkpoint inhibitors offer interesting and long-lasting response rates in heavily pretreated patients with advanced urologic cancers.

In prostate cancer, a growing body of data supports the oncologic role of anti–CTLA-4 antibodies, alone or in combination with other immune therapies. ........

In renal cancer, the most encouraging findings have been observed for PD-1/PD-L1 inhibitors given their safety and antitumor activity. .......

The field of immunotherapy in urologic cancer treatment is evolving. Oncologic efficacy, including prolongation of overall survival, has already been observed for immune checkpoint inhibitors in various malignancies, mainly in breast cancer and melanomas. Several ongoing trials are studying immune therapy combinations and immune monotherapy combined with conventional anticancer drugs (Table 4). An anti–CTLA-4 antibody and vaccine combination has already been tested with interesting outcomes. Preclinical studies also support the synergistic role of CTLA-4 and PD-1 blockade [, ].

Table 4 laat lopende studies zien, maar voor recente studies kunt u het beste kijken in clinicaltrials. :

Table 4Ongoing clinical trials
Clinical trialDrugPhaseCancerEstimated

enrollment
PopulationPrimary endpointArmsEstimated completion

date
CTLA-4
NCT01057810 Ipilimumab 3 Prostate 60 CT-naïve mCRPC OS Versus placebo February 2016
NCT01530984 Ipilimumab 2 Prostate 54 CT-naïve mCRPC PSA decline Versus ipilimumab + GM-CSF December 2018
NCT01688492 Ipilimumab 1/2 Prostate 25 CT-naïve mCRPC PSA decline With abiraterone September 2015
NCT01498978 Ipilimumab 2 Prostate 30 mCRPC PSA decline April 2018
NCT01194271 Ipilimumab 2a Prostate 20 Localized Immune response Neoadjuvant September 2015
NCT01804465 Ipilimumab 2 Prostate 66 CT-naïve mCRPC Immune response With sipuleucel-T December 2016
NCT02231749 Ipilimumab 3 RCC 1070 mRCC OS, PFS With nivolumab versus sunitinib October 2019
NCT01524991 Ipilimumab 2 Bladder 36 M OS With GC June 2016
PD-1
NCT01354431 Nivolumab 2 RCC 150 mRCC RECIST April 2015
NCT01668784 Nivolumab 3 RCC 822 mRCC RECIST Versus everolimus September 2016
NCT01441765 Pidilizumab 2 RCC 44 mRCC RECIST ± dendritic cell vaccine November 2015
NCT01420965 Pidilizumab 2 Prostate 57 mCRPC Immune response With sipuleucel ± cyclophosphamide December 2018
NCT02210117 Nivolumab 2 RCC 45 mCRPC Safety ± sunitinib versus ± ipilimumab January 2019
NCT01928394 Nivolumab 1/2 Bladder 410 M Response rate ± ipilimumab March 2017
PD-L1
NCT01984242 MPDL3280A 2 RCC 150 mRCC RECIST ± sunitinib versus bevacizumab January 2016
NCT02108652 MPDL3280A 2 Bladder 330 M Response rate March 2016
B7-H3
NCT01391143 MGA271 1 Prostate Bladder

RCC
151 M Safety February 2016

Data from studies support the activity and safety of immune checkpoint inhibitors in urologic cancers, alone or in combination with conventional cancer therapies. Encouraging data in other oncologic fields could translate into interesting responses in urological cancers.

A Systematic Review of Immunotherapy in Urologic Cancer: Evolving Roles for Targeting of CTLA-4, PD-1/PD-L1, and HLA-GInline Image eulogo1

Edgardo D. Carosella'Correspondence information about the author Edgardo D. Carosella
,
Guillaume Ploussard
,
Joel LeMaoult
,
Francois Desgrandechamps

DOI: http://dx.doi.org/10.1016/j.eururo.2015.02.032

Abstract

Context

Overexpression of immune checkpoint molecules affects tumor-specific T-cell immunity in the cancer microenvironment, and can reshape tumor progression and metastasis. Antibodies targeting checkpoints could restore antitumor immunity by blocking the inhibitory receptor-ligand interaction.

Objective

To analyze data and current trends in immune checkpoint targeting therapy for urologic cancers.

Evidence acquisition

Systematic literature search for clinical trials in the PubMed and Cochrane databases up to August 2014 according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Endpoints included oncologic results, tumor response rates, safety, and tolerability.

Evidence synthesis

Anti-CTLA-4 monotherapy has demonstrated biochemical responses in prostate cancer. One phase 3 trial assessing ipilimumab efficacy in castration-resistant disease was negative overall. Nevertheless, ipilimumab may significantly improve overall survival compared with placebo in subgroups of patients with favorable prognostic features. In renal cancer, phase 1 trials showed interesting stabilization or long-lasting objective response rates approaching 50% using anti-PD-1/PD-L1 drugs in heavily pretreated metastatic patients. In bladder cancer, one phase 2 trial indicated a good safety profile for ipilimumab as a neoadjuvant drug before radical cystectomy. Overall, immune-related effects such as colitis and dermatitis were common and well tolerated.

Conclusions

Our systematic review shows that antibodies blocking immune checkpoints offer interesting and long-lasting response rates in heavily pretreated patients with advanced urologic cancers. More promising results are currently provided by anti-CTLA-4 antibodies in prostate cancer and by PD-1/PD-L1 inhibitors in renal cancer. These should encourage new clinical trials of immune therapy combinations and immunotherapy monotherapy combined with conventional anticancer drugs. In bladder cancer, the use of targeted immunotherapy still remains underevaluated; however, preliminary results reported at recent conferences seem encouraging.

Patient summary

Data from studies support the activity and safety of immune checkpoint inhibitors in urologic cancers, alone or in combination with conventional cancer therapies. Encouraging data in other oncologic fields could translate into interesting responses in urological cancers.

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