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

Lees ook dit artikel: 

https://kanker-actueel.nl/onderhoudsbehandeling-met-tcm-chinese-kruiden-na-chemotherapie-bij-longkanker-geeft-significant-betere-overall-overleving-en-veel-betere-kwaliteit-van-leven.html

Zie ook in gerelateerde artikelen

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
    Search for articles by this author
  • Yi-Long Wu
    Affiliations
    Department of Pulmonary Oncology, Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guandong, China
    Search for articles by this author
    Show all authors
  • 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.

References

    • Schiller JH
    • Harrington D
    • Belani CP
    • et al.
    Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer.
    N Engl J Med. 2002; 346: 92-98
    • Mok TS
    • Wu YL
    • Thongprasert S
    • et al.
    Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma.
    N Engl J Med. 2009; 361: 947-957
    • Maemondo M
    • Inoue A
    • Kobayashi K
    • et al.
    Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR.
    N Engl J Med. 2010; 362: 2380-2388
    • Rosell R
    • Carcereny E
    • Gervais R
    • et al.
    Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial.
    Lancet Oncol. 2012; 13: 239-246
    • Solomon BJ
    • Mok T
    • Kim DW
    • et al.
    First-line crizotinib versus chemotherapy in ALK-positive lung cancer.
    N Engl J Med. 2014; 371: 2167-2177
    • Peters S
    • Camidge DR
    • Shaw AT
    • et al.
    Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer.
    N Engl J Med. 2017; 377: 829-838
    • Soria JC
    • Tan DSW
    • Chiari R
    • et al.
    First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study.
    Lancet. 2017; 389: 917-929
    • Garon EB
    • Rizvi NA
    • Hui R
    • et al.
    Pembrolizumab for the treatment of non-small-cell lung cancer.
    N Engl J Med. 2015; 372: 2018-2028
    • Herbst RS
    • Baas P
    • Kim DW
    • et al.
    Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial.
    Lancet. 2016; 387: 1540-1550
    • Reck M
    • Rodriguez-Abreu D
    • Robinson AG
    • et al.
    Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer.
    N Engl J Med. 2016; 375: 1823-1833
    • Reck M
    • Rodríguez-Abreu D
    • Robinson AG
    • et al.
    Updated analysis of KEYNOTE-024: pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater.
    J Clin Oncol. 2019; 37: 537-546
    • Roach C
    • Zhang N
    • Corigliano E
    • et al.
    Development of a companion diagnostic PD-L1 immunohistochemistry assay for pembrolizumab therapy in non-small-cell lung cancer.
    Appl Immunohistochem Mol Morphol. 2016; 24: 392-397
    • Carbone DP
    • Reck M
    • Paz-Ares L
    • et al.
    First-line nivolumab in stage IV or recurrent non-small-cell lung cancer.
    N Engl J Med. 2017; 376: 2415-2426
    • Efron B
    The efficiency of Cox's likelihood function for censored data.
    J Am Stat Assoc. 1977; 72: 557-565
    • Miettinen OS
    • Nurminen M
    Comparative analysis of two rates.
    Stat Med. 1985; 4: 213-226
    • Hwang IK
    • Shih WJ
    • DeCani JS
    Group sequential designs using a family of type I error probability spending functions.
    Stat Med. 1990; 9: 1439-1445
    • Goffin J
    • Lacchetti C
    • Ellis PM
    • et al.
    First-line systemic chemotherapy in the treatment of advanced non-small cell lung cancer: a systematic review.
    J Thorac Oncol. 2010; 5: 260-274
    • Gandhi L
    • Rodriguez-Abreu D
    • Gadgeel S
    • et al.
    Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer.
    N Engl J Med. 2018; 378: 2078-2092
    • Davies J
    • Patel M
    • Gridelli C
    • de Marinis F
    • Waterkamp D
    • McCusker ME
    Real-world treatment patterns for patients receiving second-line and third-line treatment for advanced non-small cell lung cancer: a systematic review of recently published studies.
    PLoS One. 2017; 12: e0175679
    • Lazzari C
    • Bulotta A
    • Ducceschi M
    • et al.
    Historical evolution of second-line therapy in non-small cell lung cancer.
    Front Med (Lausanne). 2017; 4: 4
    • Borghaei H
    • Paz-Ares L
    • Horn L
    • et al.
    Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer.
    N Engl J Med. 2015; 373: 1627-1639
    • Motzer RJ
    • Escudier B
    • McDermott DF
    • et al.
    Nivolumab versus everolimus in advanced renal-cell carcinoma.
    N Engl J Med. 2015; 373: 1803-1813
    • Ferris RL
    • Blumenschein Jr, G
    • Fayette J
    • et al.
    Nivolumab for recurrent squamous-cell carcinoma of the head and neck.
    N Engl J Med. 2016; 375: 1856-1867
    • Bellmunt J
    • de Wit R
    • Vaughn DJ
    • et al.
    Pembrolizumab as second-line therapy for advanced urothelial carcinoma.
    N Engl J Med. 2017; 376: 1015-1026
    • Paz-Ares LG
    • Luft A
    • Vicente D
    • et al.
    Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer.
    N Engl J Med. 2018; 379: 2040-2051
    • Sandler A
    • Gray R
    • Perry MC
    • et al.
    Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer.
    N Engl J Med. 2006; 355: 2542-2550
    • Zinner RG
    • Obasaju CK
    • Spigel DR
    • et al.
    PRONOUNCE: randomized, open-label, phase III study of first-line pemetrexed + carboplatin followed by maintenance pemetrexed versus paclitaxel + carboplatin + bevacizumab followed by maintenance bevacizumab in patients with advanced nonsquamous non-small-cell lung cancer.
    J Thorac Oncol. 2015; 10: 134-142

Linked Articles


Plaats een reactie ...

Reageer op "Immuuntherapie met alleen Pembrolizumab geeft betere overall overleving in vergelijking met chemo voor onbehandelde patienten met uitgezaaide niet-kleincellige longkanker. Ook bij patienten met weinig PD-L1–Expressie"


Gerelateerde artikelen