Continuous EGFR tyrosine kinase inhibitor treatment with or without chemotherapy beyond gradual progression in non-small cell lung cancer patients

Figures & data

Table 1 Characteristics of patients

Characteristics	TKI n=36	TKI + chemo n=14	P-value
Sex			0.919
Male	16 (44.4)	6 (42.9)
Female	20 (55.6)	8 (57.1)
Age, years			0.295
Mean ± SD	57.39±12.34	54.71±5.50
Min, max	36, 83	47, 66
Histology			0.186
Adenocarcinoma	35 (97.2)	12 (85.7)
Squamous	1 (2.8)	2 (14.3)
Mutation status			0.915
Exon 19	12 (33.3)	4 (28.6)
L858R	6 (16.7)	2 (14.3)
Wide type	1 (2.8)	1 (7.1)
Unknown	17 (48.6)	7 (50.0)
Smoking	14 (38.9)	4 (28.6)	0.495
Tumor burden			0.540
1	1 (2.8)	0 (0.0)
2	18 (50.0)	5 (35.7)
3	17 (47.2)	9 (64.3)
TKI drug			0.562
First line	14 (38.9)	6 (42.9)
Second line	15 (41.7)	7 (50.0)
Third line	7 (19.4)	1 (7.1)
Type of TKI			0.542
Erlotinib	4 (11.1)	2 (14.3)
Gefitinib	2 (5.6)	2 (14.3)
Icotinib	30 (83.3)	10 (71.4)
TKI treatment duration (days)			0.029
Median (P25, P75)	482 (352, 605)	374 (269, 438)
Min, max	212, 1,427	182, 855

Notes: Data were expressed as mean ± SD or median (P₂₅, P₇₅) for continuous variables with normal or non-normal distribution and compared between groups using the independent Student’s t-test or Mann–Whitney U test accordingly. Categorical variables were expressed as n (%) and compared between groups using Pearson’s chi-square test or Fisher’s exact test when appropriate.

Abbreviations: P₂₅, the 25th percentile; P₇₅, the 75th percentile; SD, standard deviation; TKI, tyrosine kinase inhibitor.

Figure 1 Survival curve of PFS1 between TKI and TKI + chemo.

Abbreviations: CI, confidence interval; TKI, tyrosine kinase inhibitor; PFS, progression-free survival; chemo, chemotherapy.

Figure 2 Survival curve of PFS2 between TKI and TKI + chemo.

Abbreviations: CI, confidence interval; TKI, tyrosine kinase inhibitor; PFS, progression-free survival; chemo, chemotherapy.

Figure 3 Survival curve of PFS1 to PFS2 between TKI and TKI + chemo.

Abbreviations: CI, confidence interval; TKI, tyrosine kinase inhibitor; PFS, progression-free survival; chemo, chemotherapy.

Figure 4 Survival curve of OS between TKI and TKI + chemo.

Abbreviations: CI, confidence interval; TKI, tyrosine kinase inhibitor; chemo, chemotherapy; OS, overall survival.

Table 2 Prognosis of treatment

Survival characteristics	TKI n=36	TKI + chemo n=14	TKI + chemo vs TKI			Log-rank test
			HR	95% CI	P-value	χ^2	P-value
PFS1 (days)
Median (P25, P75)	360 (250, 482)	262 (226, 364)	2.12	1.10–4.07	0.024	5.318	0.021
PFS2 (days)
Median (P25, P75)	481 (352, 566)	395 (277, 460)	1.85	0.97–3.51	0.060	3.655	0.056
PFS1 to PFS2 (days)
Median (P25, P75)	92 (54, 196)	37 (27, 156)	1.16	0.61–2.21	0.652	0.205	0.650
OS (days)
Median (P25, P75)	696 (503, 981)	799 (618, 911)	0.76	0.33–1.71	0.501	0.457	0.499

Notes: We assessed the median time of progression-free survival and overall survival with the Kaplan–Meier method. We estimated the HRs and corresponding 95% CI values with the Cox proportional hazard regression model. We used SPSS (version 19.0; IBM Corp., Armonk. NY, USA) for all statistical analyses and P<0.05 was considered statistically significant.

Abbreviations: P₂₅, the 25th percentile; P₇₅, the 75th percentile; HR, hazard ratio, CI, confidence interval; SD, standard deviation; TKI, tyrosine kinase inhibitor; OS, overall survival; PFS, progression-free survival; chemo, chemotherapy.

Table 3 Subgroup analysis according to EGFR mutation status

Survival characteristics	EGFR mutation n=26	No EGFR mutation n=24	P-value
PFS1 (days)	276 (223, 369)	368 (275, 484)	0.032
PFS2 (days)	389 (288, 545)	470 (378, 545)	0.075
PFS1 to PFS2 (days)	87 (53, 143)	85 (31, 156)	0.955
OS (days)	729 (520, 911)	792 (609, 1,323)	0.170

Notes: The median time of progression-free survival and overall survival with the Kaplan–Meier method was assessed. Data were expressed as median (P25, P75). We used SPSS (version 19.0; IBM Corp., Armonk, NY, USA) for all statistical analyses and P<0.05 was considered statistically significant.

Abbreviations: EGFR, epidermal growth factor receptor; OS, overall survival; PFS, progression-free survival.

Table 4 Toxicity profile in all treatment courses

Type of toxicity	TKI			TKI + chemo
	Toxicity grade (%, n=36)			Toxicity grade (%, n=14)
	1–2	3	4	1–2	3	4
Hematological
Neutropenia	11.1	0	0	71.4	35.8	0
Anemia	16.7	0	0	42.8	7.1	0
Thrombocytopenia	5.5	0	0	14.3	0	0
Non-hematological
Weight loss	25	0	0	57.1	7.1	0
Anorexia	13.9	0	0	42.9	14.3	0
Fatigue	25	0	0	42.9	28.6	0
ALT/AST	27.8	11.1	0	21.4	0	0
Nausea	13.9	0	0	50	14.2	0
Vomiting	5.6	0	0	35.8	7.1	0
Diarrhea	33.3	0	0	28.6	0	0
Mucositis	38.9	0	0	35.8	0	0
Skin rash	30.6	8.3	0	42.9	28.6	0

Note: Numbers denote the highest grade in each patient.

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; TKI, tyrosine kinase inhibitor; chemo, chemotherapy.