Raadpleeg ook literatuurlijsten niet-toxische middelen en behandelingen van arts-bioloog drs. Engelbert Valstar

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15 april 2019: Bron: The Lancet

Immuuntherapie met alleen het anti-PD medicijn pembrolizumab geeft veel betere mediane overall overleving dan chemokuren bij patienten met reeds bij de diagnose uitgezaaide niet-kleincellige longkanker. Zelfs in de groep patiënten met weinig expressie van de zogeheten PD-1-L1 ligand deden de patienten het beter met allleen pembrolizumab dan met chemokuren.

Dat blijkt uit de resultaten van een grote fase III studie met totaal 1274 patiënten met uitgezaaide niet-kleincellige longkanker geanalyseerd over verschillende groepen met weinig tot veel PD-1-L1 ligand expressie.

Vanaf december 2014, tot maart 2017, werden 1274 patients (902 mannen, 372 vrouwen, mediane leeftijd 63 jaar [IQR 57-69]) met een PD-L1 expressie van 1 procent of hoger gerandomiseerd ingedeeld om of pembrolizumab (n=637) of chemotherapie (n=637) te krijgen als eerstelijns behandeling.

599 patiënten (47%) hadden een PD-1-L1 ligand expressie van 50% of meer en 818 patients (64%) had een  PD-1-L1 ligand expressie van 20% of meer. Alle patienten werden behandeld met de intentie tot genezen. Zie het studieprotocol NCT02220894.

Wat opvalt is dat ook patiënten met een relatief lage PD-1-L1 expressie (zelfs patienten met een expressie van 1 procent of zelfs geen expressie) ook uitstekend reageerden op de pembrolizumab. Weliswaar wat minder dan de patienten met een hoge expressie maar toch.  De onderzoekers adviseren dan ook om pembrolizumab als eerstelijns te geven, ook als er geen PD-1L1 expressie is. 

The benefit-to-risk profile suggests that pembrolizumab monotherapy can be extended as first-line therapy to patients with locally advanced or metastatic non-small-cell lung cancer without sensitising EGFR or ALK alterations and with low PD-L1 TPS.

Het volledige studierapport: 

Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial is tegen betaling in te zien.

Hier het abstract van de studie:

Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial

  • Tony S K Mok
    Correspondence
    Correspondence to: Prof Tony S K Mok, Department of Clinical Oncology, State Key Laboratory of South China, Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region, China
    Affiliations
    Department of Clinical Oncology, State Key Laboratory of South China, Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region, China
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  • Yi-Long Wu
    Affiliations
    Department of Pulmonary Oncology, Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guandong, China
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  • Author Footnotes
    † A complete list of investigators is provided in the appendix

BACKGROUND

First-line pembrolizumab monotherapy improves overall and progression-free survival in patients with untreated metastatic non-small-cell lung cancer with a programmed death ligand 1 (PD-L1) tumour proportion score (TPS) of 50% or greater. We investigated overall survival after treatment with pembrolizumab monotherapy in patients with a PD-L1 TPS of 1% or greater.

METHODS

This randomised, open-label, phase 3 study was done in 213 medical centres in 32 countries. Eligible patients were adults (≥18 years) with previously untreated locally advanced or metastatic non-small-cell lung cancer without a sensitising EGFR mutation or ALK translocation and with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, life expectancy 3 months or longer, and a PD-L1 TPS of 1% or greater. Randomisation was computer generated, accessed via an interactive voice-response and integrated web-response system, and stratified by region of enrolment (east Asia vs rest of world), ECOG performance status score (0 vs 1), histology (squamous vs non-squamous), and PD-L1 TPS (≥50% vs 1-49%). Enrolled patients were randomly assigned 1:1 in blocks of four per stratum to receive pembrolizumab 200 mg every 3 weeks for up to 35 cycles or the investigator's choice of platinum-based chemotherapy for four to six cycles. Primary endpoints were overall survival in patients with a TPS of 50% or greater, 20% or greater, and 1% or greater (one-sided significance thresholds, p=0·0122, p=0·0120, and p=0·0124, respectively) in the intention-to-treat population, assessed sequentially if the previous findings were significant.

FINDINGS

From Dec 19, 2014, to March 6, 2017, 1274 patients (902 men, 372 women, median age 63 years [IQR 57-69]) with a PD-L1 TPS of 1% or greater were allocated to pembrolizumab (n=637) or chemotherapy (n=637) and included in the intention-to-treat population. 599 (47%) had a TPS of 50% or greater and 818 patients (64%) had a TPS of 20% or greater. As of Feb 26, 2018, median follow-up was 12·8 months. Overall survival was significantly longer in the pembrolizumab group than in the chemotherapy group in all three TPS populations (≥50% hazard ratio 0·69, 95% CI 0·56-0·85, p=0·0003; ≥20% 0·77, 0·64-0·92, p=0·0020, and ≥1% 0·81, 0·71-0·93, p=0·0018). The median surival values by TPS population were 20·0 months (95% CI 15·4-24·9) for pembrolizumab versus 12·2 months (10·4-14·2) for chemotherapy, 17·7 months (15·3-22·1) versus 13·0 months (11·6-15·3), and 16·7 months (13·9-19·7) versus 12·1 months (11·3-13·3), respectively. Treatment-related adverse events of grade 3 or worse occurred in 113 (18%) of 636 treated patients in the pembrolizumab group and in 252 (41%) of 615 in the chemotherapy group and led to death in 13 (2%) and 14 (2%) patients, respectively.

INTERPRETATION

The benefit-to-risk profile suggests that pembrolizumab monotherapy can be extended as first-line therapy to patients with locally advanced or metastatic non-small-cell lung cancer without sensitising EGFR or ALK alterations and with low PD-L1 TPS.

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