Management of acquired resistance to EGFR TKI–targeted therapy in advanced non-small cell lung cancer

Table 2 Different generations of EGFR TKIs

Generation	EGFR inhibition	Drug	Molecular Targets^a	Adverse effect	Status
1st-generation	Reversible;	Gefitinib	EGFR del19, L858R	Skin rash/acne, abnormal LFT	FDA approved
1st-generation	competitive	Erlotinib	EGFR del19, L858R		FDA approved
2nd-generation	Irreversible; covalent	Afatinib	EGFR del19, L858R, uncommon mutations, HER2, HER4	Diarrhea, paronychia. Skin rash	FDA approved
		Dacomitinib	EGFR del19, L858R, HER2, HER4	Diarrhea, skin rash/acne	Phase III
		Neratinib	EGFR G719X, HER2, HER4	Diarrhea, dyspnea, N/V	Phase II
3rd-generation	Irreversible;	Osimertinib	EGFR mutations and T790M	Diarrhea, skin rash	FDA approved
	covalent	Rociletinib	EGFR T790M mutation, IGF-1R	Hyperglycemia, QTc prolong	Withdrawn
		Olmutinib	EGFR T790M mutation	Diarrhea, skin exfoliation, nausea	Approved in South Korea
		ASP8273	EGFR L858R, del19, T790M,	Diarrhea, N/V, thrombocytopenia	Phase III Discontinued
		Nazartinib	EGFR L858R, del19, T790M,	Rash, diarrhea, pruritus	Phase I/II
		Avitinib (AC0010)	EGFR L858R, del19, T790M,	Diarrhea, skin rash, abnormal LFT	Phase I/II
		HS-10296	EGFR sensitive mutations (G719X, del19, L858R, L861Q) +/− T790M	None reported	Phase I/II
		PF-06747775	EGFR L858R, del19, T790M,	None reported	Phase I/II

N/V nausea and/or vomiting, LFT liver function test, del19 deletion in exon19, EGFR epidermal growth factor receptor, FDA Food and Drug Administration
^aThe targets included FDA approved or associated targets

ISSN: 1476-4598