Mutation abundance affects the therapeutic efficacy of EGFR-TKI in patients with advanced lung adenocarcinoma: A retrospective analysis

Figures & data

Figure 1. Flow diagram of patients enrolled in the study.

Table 1. Baseline demographic and clinical characteristics.

Clinical characteristics	Patients (n)	Percentage (%)
Age in years
≥ 60	114	58.8%
< 60	80	41.2%
Gender
Male	78	40.2%
Female	116	59.8%
Smoking history
Yes	52	26.8%
No	142	73.2%
Mutational sites
Exon 19 deletion	98	50.5%
Exon 21 mutation	96	49.5%
EGFR-TKI used as first line treatment or not
First line	102	52.6%
Second line or others	92	47.4%
Pathological type
Pure adenocarcinoma	190	97.9%
Containing adenocarcinoma components	4	2.1%
TNM stages (optimal)
IIIB stage	37	19.1%
IV stage	157	80.9%
ECOG
0–2 points	173	89.2%
3 points	21	10.8%

ECOG denotes the Eastern Cooperative Oncology Group.

Table 2. The association between PFS and mutation abundance after EGFR-TKI therapy.

	Percentage	Median time	Median PFS
	(n = 194, %)	(range)	(months)	95% CI	P-value
Time of follow-up (months)	194 (100)	18.1 (7.1–33.0)	9.3	8.2–10.8
Overall disease control rate	174 (89.2)
Progression of disease (up to deadline of follow up)	145 (74.7)
EGFR mutation abundance (exon 21 mutation or exon 19 deletion)					0.014
< 10% (n = 41)	41 (21.1)		5.53	1.68–9.39
≥ 10%, < 20% (n = 30)	30 (15.5)		8.23	3.56–12.90
≥ 20%, < 30% (n = 39)	39 (20.1)		9.6	7.85–11.35
≥ 30%, < 40% (n = 33)	33 (17.0)		14.8	6.70–22.67
≥ 40%, < 50% (n = 24)	24 (12.4)		10.8	5.89–15.77
≥ 50% (n = 27)	27 (13.9)		9.1	6.65–11.61

Table 3. Risk factors to PFS by univariate analysis.

Clinical characteristics	HR (95% CI)	P-value
Age in years
≥ 60	1.0
< 60	1.16 (0.83–1.63)	0.379
Gender
Female	1.0
Male	1.09 (0.78–1.53)	0.620
Smoking history
Yes	1.0
No	1.14 (0.78–1.67)	0.508
Mutational sites
Exon 21 mutation	1.0
Exon 19 deletion	0.81 (0.59–1.13)	0.214
EGFR-TKI used as first line treatment or not
First line	1.0
Second line or others	0.88 (0.63–1.22)	0.439
EGFR deletion/mutation abundance (Exon 19 or Exon 21)
≥ 30%	1.0
< 30%	1.64 (1.17– 2.31)	0.005

ECOG denotes the Eastern Cooperative Oncology Group.

Figure 2. The cut-off value of EGFR (exon19 and exon21) mutation abundance with ROC curve analysis.

Table 4. The cut-off value of EGFR mutation abundance to the PFS by ROC analysis.

Clinical characteristics	HR (95% CI)	P-value	ORRs	DCR
EGFR deletion/mutation abundance (Exon 19 or Exon 21)			61.9%	89.2%
≤ 26.7%	1.0		45.5%	83.2%
> 26.7%	1.71 (1.22–2.40)	0.002	79.6%	95.7%
EGFR deletion abundance (Exon 19)			76.5%	92.9%
≤ 61.8%	1.0		76.1%	92.0%
> 61.8%	0.57 (0.29–1.13)	0.107	80.0%	100.0%
EGFR mutation abundance (Exon 21)			46.9%	85.4%
≤ 10.2%	1.0		24.2%	72.7%
>10.2%	1.55 (0.97–2.49)	0.070	58.7%	92.1%

ORRs: objective response rates; HR: hazard ratio; DCR: disease control rate.

Table 5. Cox regression survival analysis of correlations between EGFR mutation abundance cut-off values and PFS by after adjusting the influence of age, gender and other general factors.

Clinical characteristics	HR (95% CI)	P-value
EGFR mutation abundance (Exon 19 or Exon 21)
≤ 26.7%	1.0
> 26.7%	1.75 (1.24–2.47)	0.0016
EGFR deletion abundance (Exon 19)
≤ 61.8%	1.0
> 61.8%	0.63 (0.31–1.28)	0.2015
EGFR mutation abundance (Exon 21)
≤ 10.2%	1.0
>10.2%	1.54 (0.95–2.48)	0.0809

Figure 3. Survival analysis of the effects of EGFR-TKI A) first line or B) non-first line treatments on high and low EGFR mutation abundance NSCLC patients.

Table 6. The distribution of EGFR mutation sites and mutation abundance in 861 patients.

EGFR mutation abundance	Case	EGFR exon 19 deletion (n, %)	EGFR exon 21 mutation (n, %)	P-value
< 10%	206	59 (28.6)	147 (71.4)	< 0.000
10–20%	174	70 (40.2)	104 (59.8)
20–30%	166	84 (50.6)	82 (49.4)
30–40%	117	71 (60.7)	46 (39.3)
40–50%	77	52 (67.5)	25 (32.5)
50–60%	46	29 (63.0)	17 (37.0)
60–70%	25	21 (84.0)	4 (16.0)
> 70%	17	14 (82.4)	3 (17.6)

Figure 4. Kaplan-Meier curves for median PFS in high and low mutation abundance patients with A) exon 19 deletions or exon 21 mutations, B) exon 19 deletions and C) exon 21 mutations.