KEYNOTE-189: Pembrolizumab plus Pemetrexed and Platinum versus placebo plus Pemetrexed and Platinum for untreated, metastatic nonsquamous non-small cell lung cancer
In KEYNOTE-189, Pembrolizumab ( Keytruda ) plus Pemetrexed ( Alimta ) and Platinum provided superior overall survival ( OS ) ( hazard ratio, HR 0.49, P less than 0.00001 ) and progression-free survival ( PFS ) ( HR 0.52, P less than 0.00001 ) and had manageable safety vs placebo plus Pemetrexed and Platinum as first-line therapy for metastatic nonsquamous NSCLC.
In an exploratory analysis, researchers assessed outcomes by investigator’s choice of Carboplatin or Cisplatin.
616 patients with untreated metastatic nonsquamous NSCLC regardless of PD-L1 TPS without sensitizing EGFR or ALK alteration were randomized 2:1 to 4 Q3W cycles of Pembrolizumab 200 mg or placebo plus Pemetrexed 500 mg/m2 plus Carboplatin AUC 5 or Cisplatin 75 mg/m2 followed by maintenance Pembrolizumab or placebo plus Pemetrexed.
Randomization was stratified by TPS ( less than 1% vs greater than or equal to 1% ), Platinum ( Carboplatin vs Cisplatin ), and smoking status ( current / former vs never ).
Primary end points were overall survival and progression-free survival; objective response rate ( ORR ) and safety were secondary.
Carboplatin was chosen for 72% of patients in both arms.
OS, PFS, and ORR were improved in the Pembrolizumab plus Pemetrexed and Platinum arm in both Carboplatin and Cisplatin recipients.
In the Pembrolizumab vs placebo arm, 83% vs 72% received 4 Carboplatin doses and 81% vs 79% received 4 Cisplatin doses.
76% vs 65% and 78% vs 72%, respectively, received greater than or equal to 5 Pemetrexed doses.
Grade 3-5 adverse events rates for Pembrolizumab vs placebo were 70% vs 66% with Carboplatin and 59% vs 65% with Cisplatin.
Rates of the most common any-grade adverse events were generally similar for Carboplatin and Cisplatin: nausea 54% with Pembrolizumab vs 48% with placebo for Carboplatin and 60% vs 63% for Cisplatin, anemia 45% vs 48% and 50% vs 44%, and fatigue 44% vs 43% and 33% vs 26%.
Rates of acute kidney injury in the Pembrolizumab arm were 5.1% with Carboplatin and 5.4% with Cisplatin.
In conclusion, Pembrolizumab plus Pemetrexed and Platinum improved efficacy and was generally tolerable compared with placebo plus Pembrolizumab and Platinum regardless of the chosen Platinum.
These data support the use of both Carboplatin and Cisplatin in combination with Pembrolizumab and Pemetrexed as first-line therapy for metastatic nonsquamous NSCLC. ( Xagena )
Source: ESMO ( European Society for Medical Oncology ) Meeting, 2018
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