Comparing the efficacy of concurrent EGFR-TKI and whole-brain radiotherapy vs EGFR-TKI alone as a first-line therapy for advanced EGFR-mutated non-small-cell lung cancer with brain metastases: a retrospective cohort study

Figures & data

Table 1 Clinicopathologic characteristics of the study subjects

Characteristics	Total subjects (N=104)	EGFR-TKI plus WBRT (n=56)		EGFR-TKI (n=48)		P-value
		No. of patients	%	No. of patients	%
Gender
Male	45	25	55.6	20	44.4	0.843
Female	59	31	52.5	28	47.5
Age (years)
>60	37	19	51.2	18	48.6	0.837
≤60	67	37		30
ECOG-PS score
0–1	92	48	52.2	44	47.8	0.377
≥2	12	8	66.7	4	33.3
Symptomatic brain metastasis
Yes	48	29	60.4	19	39.6	0.241
No	56	27	48.2	29	51.8
Smoking status
Never	77	41	53.2	36	46.8	0.836
Former	27	15	55.6	12	44.4
EGFR mutations
19 del	39	18	46.2	21	53.8	0.173
L858R	39	20	51.3	19	48.7
Others	26	18	69.2	8	30.8
Extracranial metastasis initially
Yes	83	45	54.2	38	45.8	0.880
No	21	11	52.3	10	47.6
Number of brain metastases, n
>3	70	30	42.9	40	57.1	0.403
≤3	34	16	47.1	18	52.9
Histology
Adenocarcinoma	101	56	55.4	45	44.6	0.095
Others	3	0	0	3	100

Abbreviations: ECOG-PS, Eastern Cooperative Oncology Group Performance Status; TKI, tyrosine kinase inhibitor; WBRT, whole-brain radiotherapy.

Table 2 iPFS and OS according to subgroups

	n	Median iPFS (months)	95% CI	P-value	Median OS (months)	95% CI	P-value
Gender
Male	45	14.2	9.362–19.038	0.584	25.5	17.718–33.282	0.380
Female	59	15.1	13.683–16.517		28.0	21.150–34.850
Age (years)
>60	37	17.6	11.421–16.579	0.649	28.3	21.815–34.785	0.326
≤60	67	14.0	13.037–22.163		25.5	29.575–31.425
ECOG-PS
0–1	92	14.5	11.291–17.709	0.952	25.4	20.760–30.040	0.198
≥2	12	14.5	4.316–24.684		25.5	2.705–48.295
Symptomatic of BM
Yes	36	17.6	13.787–21.413	0.218	28.0	24.122–31.878	0.953
No	68	14.0	10.780–17.220		25.4	19.988–30.812
Smoking status
Never	77	14.5	11.882–17.118	0.996	27.3	22.842–31.758	0.761
Former	27	16.1	9.124–23.076		25.5	16.953–34.047
EGFR mutations
19 del	39	14.5	11.634–16.214	0.915	27.5	17.050–38.365	0.356
L858R	39	15.1	13.852–16.786		22.1	17.552–26.865
Other	26	17.2	12.466–21.756		28.2	23.678–32.986
Extracranial metastasis initially
Yes	83	14.5	11.031–17.969	0.362	24.0	18.579–29.421	0.203
No	21	15.1	6.179–24.021		28.4	24.543–32.257
Number of BMs
>3	70	12.5	12.952–17.432	0.044	27.3	21.633–32.967	0.696
≤3	34	18.0	16.142–23.554		30.0	21.027–38.973
Therapy method
EGFR-TKI plus WBRT	56	17.7	16.288–22.212	0.015	28.1	23.975–32.225	0.756
EGFR-TKI alone	48	11.0	8.067–13.933		24.0	17.428–30.572

Abbreviations: ECOG-PS, Eastern Cooperative Oncology Group Performance Status; iPFS, intracranial progression-free survival; OS, overall survival; PFS, progression-free survival; TKI, tyrosine kinase inhibitor; WBRT, whole-brain radiotherapy.

Figure 1 Kaplan–Meier curves for iPFS in advanced EGFR-mutant NSCLC patients.

Notes: The median iPFS is significantly longer in patients receiving concurrent EGFR-TKIs and WBRT than in those given EGFR-TKIs alone (17.7 vs 11.0 months, P=0.015).

Abbreviations: iPFS, intracranial progression-free survival; NSCLC, non-small-cell lung cancer; TKI, tyrosine kinase inhibitor; WBRT, whole-brain radiotherapy.

Figure 2 Kaplan–Meier curves for iPFS in advanced EGFR-mutant NSCLC patients with various number of brain metastases.

Note: Patients with more than three brain metastases had significantly shorter median iPFS than those with three or less brain metastases (12.5 vs 18.0 months, P=0.044).

Abbreviations: iPFS, intracranial progression-free survival; NSCLC, non-small-cell lung cancer.

Table 3 Response to therapy in the two study cohorts

Response	EGFR-TKI plus WBRT (n=48)	EGFR-TKI alone (n=56)	Total n (%)
CR	2	4	6 (5.8%)
PR	25	22	47 (45.2%)
SD	25	20	45 (43.2%)
PD	2	2	4 (3.8%)
ORR	48.2%	54.2%	104 (100%)

Abbreviations: CR, complete response; ORR, overall response rate; PD, progressive disease; PR, partial response; SD, stable disease; TKI, tyrosine kinase inhibitor; WBRT, whole-brain radiotherapy.

Table 4 Univariable and multivariable analyses of covariables associated with intracranial progression-free survival

Characteristics	n	Univariate		Multivariate
		HR (95% CI)	P-value	HR (95% CI)	P-value
Number of brain metastasis
>3	70	1.533 (0.969–2.427)	0.068	1.785 (1.110–2.871)	0.017
≤3	34
Therapy method
EGFR-TKI + WBRT	56	0.590 (0.385–0.903)	0.015	0.504 (0.336–0.807)	0.004
EGFR-TKI	48

Abbreviations: TKI, tyrosine kinase inhibitor; WBRT, whole-brain radiotherapy.

Figure 3 Kaplan–Meier curves for OS in advanced EGFR-mutant NSCLC patients receiving various treatment regimens.

Note: The median OS did not significantly differ in patients receiving concurrent EGFR-TKIs and WBRT (median OS, 28.1 months; 95% CI, 23.975–32.225 months) and EGFR-TKIs alone (median OS, 24.0 months; 95% CI, 17.428–30.572 months), with the P-value being 0.756.

Abbreviations: NSCLC, non-small-cell lung cancer; OS, overall survival; TKI, tyrosine kinase inhibitor; WBRT, whole-brain radiotherapy.

Figure 4 Subgroup analysis of iPFS in advanced EGFR-mutant NSCLC patients with more than three brain metastases.

Note: The median iPFS was significantly longer in patients receiving concurrent EGFR-TKIs and WBRT than in those given EGFR-TKIs alone (17.6 vs 9.2 months, P=0.001).

Abbreviations: iPFS, intracranial progression-free survival; NSCLC, non-small-cell lung cancer; TKI, tyrosine kinase inhibitor; WBRT, whole-brain radiotherapy.

Figure 5 Subgroup analysis of iPFS in advanced EGFR-mutant NSCLC patients with three or less brain metastases.

Note: The median iPFS was comparable between the patients receiving concurrent EGFR-TKIs and WBRT and EGFR-TKIs alone (19.2 vs 14.5 months, P=0.526).

Abbreviations: iPFS, intracranial progression-free survival; NSCLC, non-small-cell lung cancer; TKI, tyrosine kinase inhibitor; WBRT, whole-brain radiotherapy.

Table 5 Treatment-related toxicities

	EGFR-TKI concurrent WBRT (n=56)		EGFR-TKI alone (n=48)
	Grade 1 or 2	Grade 3 or worse	Grade 1 or 2	Grade 3 or worse
Total adverse events	48/56 (85.7%)		40/48 (83.3%)
Elevated ALT/AST	15 (26.8%)	1 (1.8%)	11 (22.9%)	0
Elevated bilirubin	6 (10.7%)	0	5 (10.4%)	0
Rash	15 (26.8%)	2 (3.6%)	17 (35.4%)	1 (2.1%)
Fatigue	8 (14.3%)	0	10 (20.8%)	0
Nausea	7 (12.5%)	0	5 (10.4%)	0
Vomiting	4 (7.1%)	0	3 (6.3%)	0
Diarrhea	3 (5.4%)	1 (1.8%)	5 (10.4%)	0
Dizziness	15 (26.8%)	0	0	0
Headache	11 (19.6)	0	0	0
Cognitive disorder	3 (5.4%)	1 (1.8%)	0	0

Abbreviations: TKI, tyrosine kinase inhibitor; WBRT, whole-brain radiotherapy.