17 april 2018:

Lees ook dit artikel: 

https://kanker-actueel.nl/immuuntherapie-met-pembrolizumab-keytruda-geeft-betere-resultaten-dan-chemotherapie-als-eerstelijns-behandeling-bij-uitgezaaide-gevorderde-niet-kleincellige-longkanker-met-pd-1-mutatie.html

10 oktober 2016: Bron: ESMO en NEJM: October 9, 2016DOI: 10.1056/NEJMoa1606774

Opnieuw groot succes voor immuuntherapie met een anti-PD medicijn. Pembrolizumab (Keytruda) geeft beduidend betere resultaten dan chemo bij gevorderde niet-klein-cellige longkanker die nog niet eerder waren behandeld.

  • De 1-jaars overleving ging van 54% naar 70%,
  • de progressievrije overleving van mediaan 6 maanden naar 10,3 maanden
  • de bijwerkingen graad 3 en 4 waren de helft minder in de pembrolizumabgroep dan in de chemogroep: 27% vs 53%.
  • De deelnemende patienten (N = 305) hadden wel allemaal bij minimaal 50% of meer van hun kankercellen een positieve PD-L1 expressie. Maar deze resultaten zijn uitermate goed te noemen.

Dus naast nivolumab is nu ook pembrolizumab een werkend medicijn voor patiënten met niet-klein-cellige longkanker met een PD-L1 expressie. 

Keytruda foto

Dit zijn de resultaten zoals die op ESMO werden vrijgegeven:

In this patient population, pembrolizumab alone gave superior results to a platinum-containing doublet chemotherapy — median progression-free survival (PFS) was 10.3 vs 6 months (HR, 0.50), respectively.

The secondary endpoint of overall survival (OS) was also significantly improved with pembrolizumab. OS at 6 months was 80% vs 72% (HR, 0.60) and 1-year OS was 70% vs 54%.

The significant reduction in risk of death (by 40%) was "remarkable" as it was seen despite a high crossover rate (50%), Dr Reck commented, whereby patients in the chemotherapy group were given pembrolizumab on disease progression.

Pembrolizumab also showed a higher overall response rate (45% vs 28%) and a longer response duration (median not reached for pembrolizumab vs 6.3 months with chemotherapy).

Toxicity was lower with the immunotherapy compared with chemotherapy (grade 3/4 adverse events: 27% vs 53%), and the incidence of all adverse events was lower with immunotherapy.

Het volledige studierapport: Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer is gratis in te zien met duidelijke grafieken enz.

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Hier het abstract van de studie:

Pembrolizumab First-Line Beats Chemo: 'It's a New Day for Lung Cancer'

Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer

Martin Reck, M.D., Ph.D., Delvys Rodríguez-Abreu, M.D., Andrew G. Robinson, M.D., Rina Hui, M.B., B.S., Ph.D., Tibor Csőszi, M.D., Andrea Fülöp, M.D., Maya Gottfried, M.D., Nir Peled, M.D., Ph.D., Ali Tafreshi, M.D., Sinead Cuffe, M.D., Mary O’Brien, M.D., Suman Rao, M.D., Katsuyuki Hotta, M.D., Ph.D., Melanie A. Leiby, Ph.D., Gregory M. Lubiniecki, M.D., Yue Shentu, Ph.D., Reshma Rangwala, M.D., Ph.D., and Julie R. Brahmer, M.D., for the KEYNOTE-024 Investigators*

October 9, 2016DOI: 10.1056/NEJMoa1606774

Background

Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non–small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1).

Methods

In this open-label, phase 3 trial, we randomly assigned 305 patients who had previously untreated advanced NSCLC with PD-L1 expression on at least 50% of tumor cells and no sensitizing mutation of the epidermal growth factor receptor gene or translocation of the anaplastic lymphoma kinase gene to receive either pembrolizumab (at a fixed dose of 200 mg every 3 weeks) or the investigator’s choice of platinum-based chemotherapy. Crossover from the chemotherapy group to the pembrolizumab group was permitted in the event of disease progression. The primary end point, progression-free survival, was assessed by means of blinded, independent, central radiologic review. Secondary end points were overall survival, objective response rate, and safety.

Results

Median progression-free survival was 10.3 months (95% confidence interval , 6.7 to not reached) in the pembrolizumab group versus 6.0 months (95% CI, 4.2 to 6.2) in the chemotherapy group (hazard ratio for disease progression or death, 0.50; 95% CI, 0.37 to 0.68; P<0.001). The estimated rate of overall survival at 6 months was 80.2% in the pembrolizumab group versus 72.4% in the chemotherapy group (hazard ratio for death, 0.60; 95% CI, 0.41 to 0.89; P=0.005). The response rate was higher in the pembrolizumab group than in the chemotherapy group (44.8% vs. 27.8%), the median duration of response was longer (not reached [range, 1.9+ to 14.5+ months] vs. 6.3 months [range, 2.1+ to 12.6+]), and treatment-related adverse events of any grade were less frequent (occurring in 73.4% vs. 90.0% of patients), as were grade 3, 4, or 5 treatment-related adverse events (26.6% vs. 53.3%).

Conclusions

In patients with advanced NSCLC and PD-L1 expression on at least 50% of tumor cells, pembrolizumab was associated with significantly longer progression-free and overall survival and with fewer adverse events than was platinum-based chemotherapy. (Funded by Merck; KEYNOTE-024 ClinicalTrials.gov number, NCT02142738.)

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