TABLE 1

Epidermal growth factor receptor mutations with their relative frequency and sensitivity to tyrosine kinase inhibitor (TKI)

Mutation	Frequency	Drug activity	References
Exon 19 deletions^#	45%	Sensitive to first generation TKI	Costa et al. [13], 2007
L858R	40%		Rosell et al. [14], 2009
			Maemondo et al. [15], 2010
			Mitsudomi et al. [16], 2010
			Mok et al. [17], 2009
			Zhou et al. [18], 2011
			Sequist et al. [19], 2013
In frame insertions exon 19	2%	Sensitive to first generation TKI	He et al. [20], 2012
G719X (A/C/S)	2–3%	Sensitive to first generation TKI	Watanabe et al. [21], 2014
G719X (A/C/S)	2–3%	Possibly shorter response time	Watanabe et al. [21], 2014
L861 Q	2%	Sensitive to first generation TKI	De Pas et al. [22], 2011
L861 Q	2%	Sensitive to first generation TKI	Pao and Chmielecki [23], 2010
L861 R	Rare	Resistance?	De Pas et al. [22], 2011
Exon 20 in frame insertions	2%; up to 10% in some series	Resistance to first generation TKI	Pao and Chmielecki [23], 2010
		Some - A763_Y764insFQEA - are sensitive to TKI	Oxnard et al. [24], 2013
			Arcila et al. [25], 2013
			Yasuda et al. [26], 2012
			Yasuda et al. [27], 2013
T790M	∼50% in progressing patients under TKI Rare in untreated patients	Resistance if secondary to treatment Negative impact on response rate and survival: may sometimes respond to first generation TKI	Sun et al. [28], 2013 Yu et al. [29], 2014 Ding et al. [30], 2014
D761Y	Rare	Uncertain significance, possible partial resistance	Balak et al. [31], 2006
L747 P/S	Rare	Uncertain significance, possible partial resistance	van der Wekken et al. [32], 2012
			Costa et al. [33], 2007
			Costa et al. [34], 2008
S768I	Rare	Resistance to first generation TKI?	Shigematsu et al. [35], 2005
		Sensitive to afatinib?	De Pas et al. [22], 2011
		May occur in association with other mutations	J.C. Yang and co-workers, personal communication
E709 A/V	Rare	Resistance?	Shigematsu et al. [35], 2005
E709 A/V	Rare	Occur in association with other activating mutations	Shigematsu et al. [35], 2005
H870R	Rare	Resistance?	De Pas et al. [22], 2011
		Occur with other mutations
		Shorten response time
Other mutations: S720F, I715S, L862V, S784F	Rare	Unknown	Shigematsu et al. [35], 2005
			De Pas et al. [22], 2011
			Tsao et al. [36], 2005
			Ludovini et al. [37], 2008
Compound mutations	Frequency unknown; few data exist and are mainly based on case reports

^#:There are several variants of exon 19 in frame deletions, some of them not encompassing the LRE region. Response to therapy may be different according to mutation type [38].