27 september 2015: Bron: PLoS One. 2015 Jun 18;10(6):e0130142. doi: 10.1371/journal.pone.0130142. eCollection 2015.

De laatste jaren vindt er een enorme ontwikkeling plaats met zogeheten anti-PD medicijnen (anti programmed death) ook wel checkpoint remmers genoemd, die ingezet worden als immuuntherapeutische aanpak, zoals de bekendste nivolumab, Pembrolizumab en atezolimab voorheen MPDL3280A geheten. Maar er zijn veel meer anti-PD medicijnen in studies actief. Ik denk persoonlijk dat met deze anti-PD medicijnen een heleboel kanker onder controle kan worden gebracht omdat het werkt als een vorm van immuuntherapie waarbij het apoptose mechanisme (zelfdoding van de cel) wordt hersteld. Waardoor beschadigde cellen of cellen die hun werk hebben gedaan op een natuurlijke manier worden opgeruimd.

Ialiaanse onderzoekers hebben onderzocht of er nog verschil zit in effectiviteit en kans van aanslaan van deze medicijnen of een patiënt de zogeheten Ligand-1 receptorenstatus / DNA mutatie heeft.

Hieronder de grafiek welke studies bij welke vorm van kanker zij de data hebben verzameld. In dit geval bij melanomen, longkanker en spijsverteringskanker omdat daarin het meest bekend is van studies, maar anti-PD medicijnen werken in principe bij alle vormen van kanker met solide tumoren.

Zij ontdekten dat er wel enig verschil in zit in de kans van succes maar ook kankerpatiënten zonder de Ligand-1 receptorstatus reageren vaak goed op anti-PD medicijnen. Het is ook goed te weten dat deze anti-PD medicijnen tot nu toe ingezet worden bij mensen die al eerder meerdere behandelingen hebben gehad. Interessant zou natuurlijk zijn om deze anti-PD medicijnen in te zetten als immuuntherapie na de eerste diagnose.

Hier de grafiek van het verschil in Ligand-1 status:

Het is te veel om het studieversalg te vertalen. Zoek in onze zoekmachine op genoemde medicijnen voor studies. Het volledige studierapport: Differential Activity of Nivolumab, Pembrolizumab and MPDL3280A according to the Tumor Expression of Programmed Death-Ligand-1 (PD-L1): Sensitivity Analysis of Trials in Melanoma, Lung and Genitourinary Cancers is gratis in te zien met mooie overzichtsgrafieken en interessante referentielijst van studies met ani-PD medicijnen.

Hier het abstract van de studie:

three antibodies provide a significant differential effThe predictive value of PD-L1 on tumor cells seems to be more robust for anti-PD-1 antibody (nivolumab and pembrolizumab), and in the context of advanced melanoma and NSCLC

2015 Jun 18;10(6):e0130142. doi: 10.1371/journal.pone.0130142. eCollection 2015.

Differential Activity of Nivolumab, Pembrolizumab and MPDL3280A according to the Tumor Expression of Programmed Death-Ligand-1 (PD-L1): Sensitivity Analysis of Trials in Melanoma, Lung and Genitourinary Cancers.

Carbognin L¹, Pilotto S¹, Milella M², Vaccaro V², Brunelli M³, Caliò A³, Cuppone F⁴, Sperduti I⁵, Giannarelli D⁵, Chilosi M³, Bronte V³, Scarpa A⁶, Bria E¹, Tortora G¹.

Author information

¹Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
²Medical Oncology, Regina Elena National Cancer Institute, Roma, Italy.
³Department of Pathology and Diagnostic, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
⁴Agenzia Italiana del Farmaco (AIFA), Roma, Italy.
⁵Biostatistics, Regina Elena National Cancer Institute, Roma, Italy.
⁶Department of Pathology and Diagnostic, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy; ARC-NET Center for Applied Research on Cancer, Verona, Italy.

Abstract

BACKGROUND:

The potential predictive role of programmed death-ligand-1 (PD-L1) expression on tumor cells in the context of solid tumor treated with checkpoint inhibitors targeting the PD-1 pathway represents an issue for clinical research.

METHODS:

Overall response rate (ORR) was extracted from phase I-III trials investigating nivolumab, pembrolizumab and MPDL3280A for advanced melanoma, non-small cell lung cancer (NSCLC) and genitourinary cancer, and cumulated by adopting a fixed and random-effect model with 95% confidence interval (CI). Interaction test according to tumor PD-L1 was accomplished. A sensitivity analysis according to adopted drug, tumor type, PD-L1 cut-off and treatment line was performed.

RESULTS:

Twenty trials (1,475 patients) were identified. A significant interaction (p<0.0001) according to tumor PD-L1 expression was found in the overall sample with an ORR of 34.1% (95% CI 27.6-41.3%) in the PD-L1 positive and 19.9% (95% CI 15.4-25.3%) in the PD-L1 negative population. ORR was significantly higher in PD-L1 positive in comparison to PD-L1 negative patients for nivolumab and pembrolizumab, with an absolute difference of 16.4% and 19.5%, respectively. A significant difference in activity of 22.8% and 8.7% according to PD-L1 was found for melanoma and NSCLC, respectively, with no significant difference for genitourinary cancer.

CONCLUSION:

Overall, the three antibodies provide a significant differential effect in terms of activity according to PD-L1 expression on tumor cells. The predictive value of PD-L1 on tumor cells seems to be more robust for anti-PD-1 antibody (nivolumab and pembrolizumab), and in the context of advanced melanoma and NSCLC.

PMID:: 26086854; [PubMed - in process]
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