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

Davis, Andrew A.; Patel, Vaibhav G.

doi:10.1186/s40425-019-0768-9

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	2016^a	None	1st	0.05	Archival	IC	SP142	310	ORR	Overall 14.8% PD-L1+ 26.0% PD-L1- 9.5%
Bladder	Pembrolizumab	PD-1	2017^a	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)

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

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