26 januari 2019: lees ook dit artikel: 

https://kanker-actueel.nl/dendritische-celtherapie-heeft-succes-bij-patienten-met-mesothelioma-asbestkanker-erasmus-doet-oproep-dat-meer-patienten-zich-aanmelden-voor-de-studie.html

1 april 2017: Bron: The Lancet

Ook bij mesothelioma - asbestkanker lijkt immuuntherapie met een anti-PD medicijn, in dit geval pembrolizumab uitstekend te werken. In een kleinschalige studie met 25 patiënten die minimaal twee chemokuren en Alimta hadden gehad maar desondanks progressie van hun ziekte vertoonden bleek pembrolizumab alsnog bij 5 patienten (20 procent) voor een PR- gedeeltelijke remissie te zorgen en bij 51 procent voor stabiele ziekte = stilstand van de ziekte. Een uitstekend resultaat natuurlijk, ook omdat mesothelioma als ongeneeslijk bekend staat en de patiënten die aan de studie meededen al meerdere chemo's te verduren hadden gekregen.

Tekst gaat onder beeld verder

anti-PD medicijnen werkingsmechanisme(3)

Kernpunten uit de studie:

  • Bij patiënten met long mesothelioma, de response op pembrolizumab werd gezien bij 20% van de  patiënten. Stabiele ziekte bij 51 procent
  • De median duur van de respons duurde 12 maanden

Het volledige studierapport: Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial is tegen betlaing in te zien.

Hier het abstract van deze studie:

In an interim analysis of the phase IB KEYNOTE-028 trial reported in The Lancet Oncology, Alley et al found that pembrolizumab (Keytruda) treatment produced durable responses in patients with malignant pleural mesothelioma.

Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial

Dr Evan W Alley, MD'Correspondence information about the author Dr Evan W Alley
,
Juanita Lopez, MD
,
Prof Armando Santoro, MD
,
Anne Morosky, RN
,
Sanatan Saraf, PhD
,
Bilal Piperdi, MD
,
Emilie van Brummelen, PharmD

DOI: http://dx.doi.org/10.1016/S1470-2045(17)30169-9

Summary

Background

Malignant pleural mesothelioma is a highly aggressive cancer with poor prognosis and few treatment options following progression on platinum-containing chemotherapy. We assessed the safety and efficacy of pembrolizumab (an anti-programmed cell death receptor 1 [PD-1] antibody) in advanced solid tumours expressing programmed cell death ligand 1 (PD-L1) and report here on the interim analysis of the malignant pleural mesothelioma cohort.

Methods

Previously treated patients with PD-L1-positive malignant pleural mesothelioma were enrolled from 13 centres in six countries. Patients received pembrolizumab (10 mg/kg every 2 weeks) for up to 2 years or until confirmed progression or unacceptable toxicity. Key eligibility criteria included measurable disease, failure of standard therapy, and Eastern Cooperative Oncology Group performance status of 0 or 1. PD-L1 positivity was defined as expression in 1% or more of tumour cells by immunohistochemistry. Response was assessed based on investigator review using the Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1). Primary endpoints were safety and tolerability, analysed in the all-patients-as-treated population, and objective response, analysed for the full-analysis set. This trial is registered with ClinicalTrials.gov, number NCT02054806, and is ongoing but not recruiting participants.

Findings

As of June 20, 2016, 25 patients received pembrolizumab. 16 (64%) patients reported a treatment-related adverse event; the most common adverse event were fatigue (six [24%]), nausea (six [24%]), and arthralgia (five [20%]). Five (20%) patients reported grade 3 treatment-related adverse events. Three (12%) patients required dose interruption because of immune-related adverse events: one (4%) of 25 each had grade 3 rhabdomyolysis and grade 2 hypothyroidism; grade 3 iridocyclitis, grade 1 erythema multiforme, and grade 3 erythema; and grade 2 infusion-related reaction. No treatment-related deaths or discontinuations occurred. Five (20%) patients had a partial response, for an objective response of 20% (95% CI 6·8–40·7), and 13 (52%) of 25 had stable disease. Responses were durable (median response duration 12·0 months [95% CI 3·7 to not reached]); two patients remained on treatment at data cutoff.

Interpretation

Pembrolizumab appears to be well tolerated and might confer anti-tumour activity in patients with PD-L1-positive malignant pleural mesothelioma. Response durability and efficacy in this patient population warrants further investigation.

Funding

Merck.


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