Figure and Table | Retrospective Analysis of the Incidence of Drug-Induced Interstitial Lung Disease by Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors and Survival in Patients Aged 75 Years or Older with Lung Cancer

Table 1. Patient Characteristics.

		Gefitinib group	Erlotinib group	Afatinib group	Osimertinib group	TKI to TKI group
N		23	4	3	23	36
First-line TKI		Gefitinib	Erlotinib	Afatinib	Osimertinib	Gefitinib/Erlotinib/Afatinib/Osimeritinib: 27/5/1/3
Second-line TKI		None	None	None	None	Gefitinib/Erlotinib/Afatinib/Osimeritinib: 4/15/2/15
Age	Median (range)	79 (75-92)	79 (78-91)	77 (75-78)	77 (75-91)	78 (75-91)
Gender	Male/female	7/16	0/4	0/3	7/16	14/22
Smoking index	Median (range)	0 (0-480)	0 (0)	0 (0)	0 (0-2820)	0 (0-500)
Clinical stage	I/II/III/IV/recurrence	2/1/3/12/5	0/0/0/2/2	0/0/0/2/1	0/0/2/16/5	0/0/5/25/6
Performance status	0/1/2/3	11/8/2/2	2/1/1/0	2/1/0/0	9/11/3/0	17/19/0/0
Charlson comorbidity index	Median (range)	1 (0-10)	1 (0-1)	2 (1-2)	1 (0-4)	0 (0-3)
EGFR gene mutation	Exon19 deletion/L858R/Others	12/11/0	1/3/0	3/0/0	11/10/02	19/14/3
De novo T790M mutation		0	0	0	1	0
T790M acquisition resistance mutation		2	0	0	0	15
Treatment history of cytotoxic agents	Yes/No	3/20	1/13	2/1	4/19	19/17
Objective response rate of first-line EGFR-TKI		70%	50%	100%	74%	70%
Objective response rate of second-line EGFR-TKI		-	-	-	-	43%
Adverse events other than ILD		Rash (n = 5)	Rash (n = 1)	Diarrhea (n = 3)	Diarrhea (n = 8)	Rash (n = 14)
		Liver dysfunction (n = 3)	Paronychia (n = 1)	Nausea (n = 1)	Rash (n = 8)	Liver dysfunction (n = 5)
		Paronychia (n = 1)			Paronychia (n = 5)	Diarrhea (n = 5)
		Nausea (n = 1)			Nausea (n = 1)	Paronychia (n = 4)
		Sepsis (n = 1)				Nausea (n = 3)
						Leukocytopenia (n = 1)
Dose reduction of first-line EGFR-TKI	Yes/No	3/20	1/3	3/0	5/18	9/27
Dose reduction of second-line EGFR-TKI	Yes/No	-	-	-	-	12/24
Prognosis	Alive/Dead	11/12	2/2	1/2	12/11	13/23

Table 2. Occurrence of ILD.

EGFR-TKI causing ILD	N	P-value
First- or second-line osimertinib (n = 41)	7
First-generation TKIs (n = 78)	2	0.008

Table 3. Patients with Drug-Induced Lung Disease.

Age (years)	Gender	Performance status	Smoking index	EGFR gene mutation	Causative TKI	Duration of administration (days)	Treatment for ILD	Other adverse events (CTCAE version 5)
88	Male	2	480	Exon19 deletion	Gefitinib	327	Withdrawal of TKI	None
88	Male	1	600	Exon19 deletion	Gefitinib	855	Intravenous corticosteroid	None
84	Female	1	0	L858R	First-line osimertinib	242	Intravenous corticosteroid	None
82	Female	0	0	Exon19 deletion	First-line osimertinib	53	Intravenous corticosteroid	None
77	Female	1	0	L858R	First-line osimertinib	285	Intravenous corticosteroid	Skin rash (grade 2)
76	Male	0	2820	Exon19 deletion	First-line osimertinib	58	Withdrawal of TKI	Skin rash (grade 2)
76	Female	1	0	L858R	Second-line osimertinib	430	Withdrawal of TKI	None
87	Male	1	500	L858R	Second-line osimertinib	69	Intravenous corticosteroid	Paronychia (grade 2)
81	Male	1	450	Exon19 deletion	Second-line osimertinib	31	Intravenous corticosteroid	Aspartate aminotransferase increased (grade 1)