KEYNOTE-189 trial: Pembrolizumab improves overall survival and progression-free survival as first-line treatment in combination with Pemetrexed and Platinum chemotherapy in metastatic nonsquamous non-small cell lung cancer
The pivotal phase 3 KEYNOTE-189 trial investigating Pembrolizumab ( Keytruda ), an anti-PD-1 therapy, in combination with Pemetrexed ( Alimta ) and Cisplatin or Carboplatin, for the first-line treatment of patients with metastatic non-squamous non-small cell lung cancer ( NSCLC ), met its dual primary endpoints of overall survival ( OS ) and progression-free survival ( PFS ).
Based on an interim analysis conducted by the independent Data Monitoring Committee, treatment with Pembrolizumab in combination with Pemetrexed plus Platinum chemotherapy resulted in significantly longer OS and PFS than Pemetrexed plus Platinum chemotherapy alone.
The safety profile of Pembrolizumab in this combination was consistent with that previously observed.
KEYNOTE-189 is a randomized, double blind, placebo controlled, phase 3 study investigating Pembrolizumab in combination with Pemetrexed and Cisplatin or Carboplatin compared with Pemetrexed and Cisplatin or Carboplatin alone in patients with advanced or metastatic nonsquamous non-small cell lung cancer, regardless of PD-L1 expression.
Patients had no EGFR or ALK genomic tumor aberrations, and had not previously received systemic therapy for advanced disease.
The dual primary endpoints are OS and PFS; secondary endpoints include overall response rate ( ORR ) and duration of response ( DOR ).
The study enrolled 614 patients randomized 2:1 to receive either Pembrolizumab ( 200 mg fixed dose every three weeks ) plus Pemetrexed ( 500 mg/m2 ) ( with vitamin supplementation ) plus Cisplatin ( 75 mg/m2 ) or Carboplatin AUC 5 on day 1 every 3 weeks ( Q3W ) for 4 cycles followed by Pembrolizumab 200 mg plus Pemetrexed ( 500 mg/m2 ) Q3W or Pembrolizumab placebo 200 mg plus Pemetrexed ( 500 mg/m2 ) ( with vitamin supplementation ) plus Cisplatin ( 75 mg/m2 ) or Carboplatin AUC 5 on day 1 every 3 weeks ( Q3W ) for 4 cycles followed by Pembrolizumab placebo 200 mg plus Pemetrexed ( 500 mg/m2 ) Q3W until disease progression, unacceptable toxicity, physician decision or consent withdrawal.
Patients on the control arm who experienced disease progression, verified by central independent review, were permitted to undergo treatment assignment unblinding and crossover to receive open-label Pembrolizumab.
Pembrolizumab is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells.
Pembrolizumab is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells. ( Xagena )
Source: Merck ( MSD ), 2018