FDA approvals for immune checkpoint inhibitors linked to PD-L1 testing
| 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 trainingFresh for validation | TC | IHC 22C3 | 495 (182 training, 313 validation) | ORR | Overall19.4% overall;Training34.2% (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/kgHR 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 | 30505 | 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 | Overall14.8%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:Overall21.1% vs. 11.4% (chemotherapy)CPS ≥ 10 21.6% vs. 6.7% (chemotherapy)OS:OverallHR 0.73 (95% CI, 0.59–0.91, P = 0.002)CPS ≥ 10HR 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 | Overall17.8%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 | Overall11.6%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 | Overall12.2%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:Overall56.0% vs. 45.9% (placebo arm)PD-L1+58.9% vs. 42.6% (placebo arm)PFS:OverallHR 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) |
Abbreviations: CPS combined positive score, NSCLC non-small cell lung cancer, GEJ gastroesophageal junction, IC immune cells, TC tumor cells, TPS tumor proportion score
CPS number of PD-L1+ cells (tumor, lymphocytes, and macrophages) divided by total number of cells (tumor, lymphocytes, and macrophages), multiplied by 100
TPS number of PD-L1+ tumor cells divided by total number of tumor cells, multiplied by 100
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
bAll 12 responses observed in patients with PD-L1+ tumors