Recent advances and new insights in the management of early-stage epidermal growth factor receptor-mutated non-small-cell lung cancer

Table 1 Clinical trials of adjuvant epidermal growth factor receptor-mutated tyrosine kinase inhibitors in epidermal growth factor receptor-mutated non-small-cell lung cancer

Clinical trial	Type of trial	Sample size	Primary outcome	Stage	Treatment	Previous adjuvant chemotherapy	TKI Duration	DFS	OS
BR19, Goss et al[37]	Phase III	503 (15 with EGFR mutation)	OS	IB-IIIA	Gefitinib vs placebo	Yes (17% in gefitinib arm and 17% in placebo arm)	2 yr	HR 1.84; P = 0.3951	HR: 3.16; P = 0.151
RADIANT, Kelly et al[38]	Phase III	973 (161 with EGFR mutation)	DFS (ITT population)	IB-IIIA	Erlotinib vs placebo	Yes (45.1% in erlotinib arm and 55.9% in placebo arm)1	2 yr	46.4 vs 28.5 mo; HR: 0.61; P = 0.0391	Median OS NR in both arms; HR: 1.09; P < 0.0011
SELECT, Pennell et al[39]	Phase II	100	2-yr DFS	IA-IIIA	Erlotinib	Yes (not reported)	2 yr	Mean DFS NR; 2-yr DFS 88%; 5-yr DFS 56%	Median OS NR, 5-yr OS 86%
ADJUVANT/CTONG1104, Zhong et al[40,41]	Phase III	222	DFS	II-IIIA	Gefitinib vs cisplatin-vinorelbine	No	2 yr	28.7 vs 18 mo; HR: 0.60; P = 0.00543-yr DFS 39.6% vs 32.5%; P = 0.3165-yr DFS 22.6% vs 23.2%; P = 0.928	75.5 vs 62.8 mo; HR: 0.92; P = 0.674
IMPACT, Tada et al[42]	Phase III	234	DFS	II-III	Gefitinib vs cisplatin-vinorelbine	No	2 yr	36 vs 25.2 mo; HR: 0.92; P = 0.63	Median OS NR in both arms; HR: 1.03; P = 0.89
EVAN, Yue et al[43]	Phase II	102	2-yr DFS	IIIA	Erlotinib vs cisplatin-vinorelbine	No	2 yr	42.4 vs 21 mo; HR: 0.268; P < 0.00012-yr DFS 81.4% vs 44.6%; P = 0.00543-yr DFS 54.2% vs 19.8%; P = 0.0460	Median OS NR in both arms; HR: 0.165; P = 0.0013
Neal et al[44]	Phase II	46	2-yr DFS	IA-IIIA	Afatinib 3 mo vs 2 yr	Yes (52% in 3-mo arm and 45% in 2-yr arm)	3 mo vs 2 yr	42.8 vs 58.6 mo2-yr DFS 81% vs 70%; P = 0.55	Median OS NR in both arms
ADAURA, Wu et al[45]	Phase III	682	DFS in stages II-IIIA	IB-IIIA	Osimertinib vs placebo	Yes (60% in both arms)	3 yr	Stages II-IIIA: NR vs 19.6 mo; HR: 0.17; P < 0.0012-yr DFS 90% vs 44%ITT: NR vs 27.5 mo; HR: 0.20; P < 0.0012-yr DFS 89% vs 52%	Median OS NR in both arms (immature OS data)

¹Results in EGFR-mutated population. EGFR: Epidermal growth factor receptor; DFS: Disease-free survival; HR: Hazard ratio; ITT: Intention to treat; NR: Not reached; OS: Overall survival; TKI: Tyrosine kinase inhibitor.