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Table 1 FDA approvals for immune checkpoint inhibitors linked to PD-L1 testing

From: The role of PD-L1 expression as a predictive biomarker: an analysis of all US Food and Drug Administration (FDA) approvals of immune checkpoint inhibitors

Tumor Type Drug Mechanism Approval Year Comparator Line of Therapy PD-L1 Threshold PD-L1 Tissue Testing PD-L1 Cell Staining Companion Diagnostic Number of Patients Endpoint for Approval Results
NSCLC Pembrolizumab PD-1 2015 None 2nd 0.50 Fresh or archival for training
Fresh for validation
TC IHC 22C3 495 (182 training, 313 validation) ORR Overall
19.4% overall;
Training
34.2% (TPS ≥50), 9.3% (TPS 1–49) 10.0% (TPS < 1)
Validation 45.2% (TPS ≥50), 16.5% (TPS 1–49), 10.7% (TPS < 1)
NSCLC Pembrolizumab PD-1 2016 Docetaxel 2nd 0.01 Fresh or archival TC IHC 22C3 1034 OS OS:
Pembrolizumab 2 mg/kg
HR 0.71 (95% CI, 0.58–0.88; P = 0.0008)
Pembrolizumab 10 mg/kg HR 0.61 (0.49–0.75; P < 0.0001)
NSCLC Pembrolizumab PD-1 2016 Platinum-based chemotherapy 1st 0.50 Fresh or archival TC IHC 22C3 305
05
PFS, OS PFS:
HR 0.50 (95% CI, 0.37–0.68, P < 0.001)
OS:
HR 0.60 (95% CI, 0.41–0.89, P < 0.005)
Bladder Atezolizumab PD-L1 2016a None 1st 0.05 Archival IC SP142 310 ORR Overall
14.8%
PD-L1+
26.0%
PD-L1-
9.5%
Bladder Pembrolizumab PD-1 2017a Chemotherapy of investigator’s choice 1st 0.10 Fresh or archival TC + IC IHC 22C3 542 ORR, OS ORR:
Overall
21.1% vs. 11.4% (chemotherapy)
CPS ≥ 10 21.6% vs. 6.7% (chemotherapy)
OS:
Overall
HR 0.73 (95% CI, 0.59–0.91, P = 0.002)
CPS ≥ 10
HR 0.57 (95% CI, 0.37–0.88, P = 0.005)
Bladder Durvalumab PD-L1 2017 None 2nd 0.25 Fresh or archival TC + IC SP263 191 ORR Overall
17.8%
PD-L1+
27.6%
PD-L1-
5.1%
Gastric/GEJ Pembrolizumab PD-1 2017 None 3rd 0.01 Fresh or archival TC + IC IHC 22C3 259 ORR Overall
11.6%
PD-L1+
15.5%
PD-L1-
6.4%
Cervical Pembrolizumab PD-1 2018 None 2nd 0.01 Fresh or archival TC + IC IHC 22C3 98 ORR Overall
12.2%
PD-L1+
14.6%b
Triple-negative breast cancer Atezolizumab + nab-paclitaxel PD-L1 2019 Nab-paclitaxel 1st 0.01 Fresh or archival IC SP142 451 ORR, PFS ORR:
Overall
56.0% vs. 45.9% (placebo arm)
PD-L1+
58.9% vs. 42.6% (placebo arm)
PFS:
Overall
HR 0.80 (95% CI, 0.69–0.92, P = 0.002)
PD-L1+
HR 0.62 (95% CI, 0.49–0.78, P < 0.001)
  1. Abbreviations: CPS combined positive score, NSCLC non-small cell lung cancer, GEJ gastroesophageal junction, IC immune cells, TC tumor cells, TPS tumor proportion score
  2. CPS number of PD-L1+ cells (tumor, lymphocytes, and macrophages) divided by total number of cells (tumor, lymphocytes, and macrophages), multiplied by 100
  3. TPS number of PD-L1+ tumor cells divided by total number of tumor cells, multiplied by 100
  4. aIn 2018, companion PD-L1 testing approved as first-line for cisplatin-ineligible patients with locally advanced/metastatic urothelial carcinoma including Ventana SP142 (PD-L1 > 5%) treated with atezolizumab and Dako 22C3 assay CPS > 10 treated with pembrolizumab
  5. bAll 12 responses observed in patients with PD-L1+ tumors