Table 1.

Summary of the FDA- and EMA-approved immune checkpoint inhibitors for non-small cell lung cancer (NSCLC) patients.

ICI Class	DRUG	Stage	Line	FDA Indication	EMA Indication
CTLA-4 inhibitor	Ipilimumab	IV	1st	In combination with nivolumab if tumor PD-L1 ≥1% (no EGFR or ALK mutation) In combination with nivolumab and 2 cycles of platinum-doublet chemotherapy (no EGFR or ALK mutation) [25]	In combination with nivolumab and 2 cycles of platinum-doublet chemotherapy (no EGFR or ALK mutation) [26]
PD-1 inhibitors	Nivolumab	IV	1st	In combination with ipilimumab if tumor PD-L1 ≥1% (no EGFR or ALK mutation) In combination with ipilimumab and 2 cycles of platinum-doublet chemotherapy (no EGFR or ALK mutation) [27]	In combination with ipilimumab and 2 cycles of platinum-doublet chemotherapy (no EGFR or ALK mutation) [28]
			2nd-N	As single agent if progression on or after platinum-based chemotherapy (no EGFR or ALK mutation) If EGFR or ALK mutation: as single agent if progression on corresponding FDA-approved therapy [27]	As single agent if progression on or after chemotherapy [28]
	Pembrolizumab	III *-IV	1st	In combination with pemetrexed+platinum chemotherapy in non- squamous histology (no EGFR or ALK mutation) In combination with carboplatin+nabpaclitaxel/paclitaxel in squamous histology As a single agent if tumor PD-L1 ≥1% (no EGFR or ALK mutations) [29]	In combination with pemetrexed+platinum chemotherapy in non- squamous histology (no EGFR or ALK mutation) In combination with carboplatin+nabpaclitaxel/paclitaxel in squamous histology As a single agent if tumor PD-L1 ≥50% (no EGFR or ALK mutations) [30]
			2nd-N	As a single agent if tumor PD-L1 ≥1% at progression on or after platinum-based chemotherapy If EGFR or ALK mutation: as single agent if tumor PD-L1 ≥1% and progression on corresponding FDA-approved therapy [29]	As a single agent if tumor PD-L1 ≥1% at progression after ≥1 prior chemotherapy If EGFR or ALK mutation: as single agent if tumor PD-L1 ≥1% and progression after ≥1 prior chemotherapy and target therapy [30]
	Cemiplimab	III *-IV	1st	As single agent if tumor PD-L1 ≥50% (no EGFR, ROS-1, or ALK mutations) [31]	As single agent if tumor PD-L1 ≥50% (no EGFR, ROS-1, or ALK mutations) [32]
PD-L1 inhibitors	Durvalumab	IIIA **-B	Consolidation after CH-RT	Disease not progressed following concurrent platinum-based chemo-radiotherapy [33]	Disease not progressed following platinum-based chemo-radiotherapy if tumor PD-L1 on ≥1% [34]
	Atezolizumab	IV	1st	As single agent if tumor PD-L1 ≥50% or tumor-infiltrating immune cells PD-L1 covering ≥10% of the tumor area (no EGFR or ALK mutations) In combination with bevacizumab+paclitaxel+carboplatin in non-squamous histologies (no EGFR or ALK mutations) In combination with carboplatin/nab-paclitaxel in non-squamous histologies (no EGFR or ALK mutations) [35]	As single agent if tumor PD-L1 ≥50% or tumor-infiltrating immune cells PD-L1 covering ≥10% of the tumor area (no EGFR or ALK mutations) In combination with bevacizumab+paclitaxel+carboplatin in non-squamous histologies (no EGFR or ALK mutations) In combination with carboplatin/nab-paclitaxel in non-squamous histologies (no EGFR or ALK mutations) [36]
			2nd-N	As single agent at progression during or following platinum-containing chemotherapy If EGFR or ALK mutation: as single agent or in combination, after failure of FDA-approved therapy for NSCLC harboring these aberrations [35]	As single agent at progression during or following platinum-containing chemotherapy If EGFR or ALK mutation: in combination with carboplatin bevacizumab and paclitaxel after failure of appropriate targeted therapies. As single agent at progression on chemotherapy and targeted therapy [36]

*: III stage ineligible for surgery of definitive chemo-radiotherapy, **: Unresectable. Abbreviations: CH-RT, chemo-radiotherapy.