Table 1.

Current options after progression on first-line therapy, including ICIs.

Study (Ref.)	Design	Treatment	Population	Nr.	Outcomes
Shepherd FA. et al. [13]	Prospective Randomized	Docetaxel vs. BSC	Progressed on first-line platinum-based chemotherapy	104	PFS 10.6 vs. 6.7 weeks OS 7.0 vs. 4.6 months
Schuette W. et al. [14]	Phase III	Docetaxel w. vs. 3 weekly	Progressed on first-line platinum-based chemotherapy	215	OS 6.3 vs. 9.2 months ORR 10.5% vs. 12.6%
Crinò L. et al. [15]	Phase II	Gemcitabine	stage IIIB or IV	83	mDoR 29 weeks
Yoneshima Y et al. [17]	Non inferiority Phase III	Nab-paclitaxel vs. Docetaxel	Progressed on first-line platinum-based chemotherapy	503	OS 16.2 vs. 13.6 months PFS 4.2 vs. 3.4 months ORR 29.9% vs. 15.4%
Hanna N, et al. [18]	Non inferiority Phase III	Pemetrexed vs Docetaxel	Progressed on first-line chemotherapy	571	PFS 2.9 vs 2.9 months OS 8.3 vs 7.9 months
Nokihara H, et al. [19]	Non inferiority Phase III	S-1 vs. Docetaxel	Progressed on at least first-line platinum-based chemotherapy	1154	PFS 2.86 vs. 2.89 months OS 12.75 vs. 12.52 months
LUME-Lung 1 Reck M. et al. [28]	Phase III	Docetaxel ± Nintedanib	Progressed on first-line platinum-based chemotherapy Adenocarcinomas	655	PFS 3.4 vs. 2.7 months OS 10.1 vs. 9.1 months OS 12.6 vs. 10.3 months
VARGADO Grohè C. et al. [29]	Prospective no interventional	Nintedanib + Docetaxel	Previously treated with chemotherapy-IO (cohort C)	135	DCR 72.5% PFS 4.8 months
REVEL Garon EB. [30]	Phase III	Ramucirumab ± Docetaxel	Progressed on first-line platinum-based chemotherapy	1825	PFS 4.5 vs. 3 months OS 10.5 vs. 9.1 months
ULTIMATE Cortot AB. et al. [32]	Phase III	Paclitaxel weekly vs. Docetaxel	Previously treated with 1 or 2 prior lines	166	PFS 5.4 vs. 3.9 months ORR 22.5% vs. 5.5% OS 9.9 vs. 10.8

DCR = Disease Control Rate; ORR = Overall Response Rate; OS = Overall Survival; PFS = Progression Free Survival; mDoR = median duration of response.