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Table 3 Registration trials leading to the FDA approval of PD-1/PD-L1 inhibitors in lung cancer

From: Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: a comprehensive review of registration trials and future considerations

Study/Agent Tumor (n) Line of therapy Experimental arm Control arm Primary endpoint Ref
KEYNOTE-001 (phase Ib)/pembrolizumab Advanced NSCLC (n = 550) PD-L1 positive (≥1%) progressing after platinum-based therapy Pembrolizumab 2 mg/kg every 3 weeks OR 10 mg/kg every 2 or 3 weeks   ORR 28% (95% CI 12.1-49.4%) vs. 40% (95% CI 22.4-61.2) vs. 41% (95% CI 24.7-59.3%) for PD-L1 ≥ 50%
OS 22.1 mo (treatment-naïve, 95% CI 17.1-27.2) vs. 10.6 mo (previously-treated, 95% CI 8.6-13.3) for PD-L1 ≥ 50%
21, 22
KEYNOTE-024 (phase III)/pembrolizumab Metastatic NSCLC with ≥50% PD-L1 expression (n = 305) First-line Pembrolizumab 200 mg every 3 weeks ICC (cisplatin/carboplatin + pemetrexed, cisplatin/carboplatin + gemcitabine, or carboplatin + paclitaxel) PFS 10.3 mos vs. 6.0 mos (HR 0.50, 95% CI 0.37-0.68, p < 0.001) 25
KEYNOTE-021 (phase II)/pembrolizumab Advanced NSCLC (n = 123) First line (in combination with platinum-doublet chemotherapy) Pembrolizumab 200 mg + carboplatin AUC 5 mg/ml/min + pemetrexed 500 mg/m2 every 3 weeks X4 cycles followed by pembrolizumab (24 months duration) and indefinite maintenance pemetrexed Carboplatin + pemetrexed X4 cycles followed by indefinite maintenance pemetrexed ORR 55% vs. 29% (estimated treatment difference of 26%, 95% CI 9-42%, p = 0.0016) 26
CheckMate 017 (phase III)/nivolumab Metastatic squamous NSCLC (n = 272) Previously treated with platinum-based chemo Nivolumab 3 mg/kg every 2 weeks Docetaxel 75 mg/m2 every 2 weeks OS 9.2 mo vs. 6.0 mos (HR 0.59, 95% CI 0.44-0.79, p < 0.001) 27
CheckMate 057 (phase III)/nivolumab Metastatic non-squamous NSCLC (n = 582) Previously treated with platinum-based chemo Nivolumab 3 mg/kg every 2 weeks Docetaxel 75 mg/m2 every 3 weeks OS 12.2 mos vs. 9.4 mos (HR 0.73, 96% CI 0.59-0.89, p = 0.002) 28
POPLAR (phase II)/OAK (phase III)/atezolizumab NSCLC (POPLAR n = 287, OAK n = 1225) Second-line Atezolizumab 1200 mg every 3 weeks Docetaxel 75 mg/m2 POPLAR: OS 12.6 mos vs. 9.7 mos (HR 0.7, 95% CI 0.53-0.99, p = 0.04)
OAK: OS 13.8 mos vs. 9.6 mos (HR 0.73, 95% CI 0.62-0.87, p = 0.0003)
29, 30
  1. FDA Food and Drug Administration, PD-1 programmed cell death 1, PD-L1 programmed death ligand 1, NSCLC non-small cell lung cancer, ORR overall response rate, CI confidence interval, OS overall survival, ICC investigator-choice chemotherapy, PFS progression-free survival, HR hazard ratio, AUC area under curve