Hypertension as a predictive biomarker in patients with advanced non-small-cell lung cancer treated with apatinib

Figures & data

Table 1 Patient characteristics

Characteristics	Normotensive (N=64), N (%)	Hypertensive (N=46), N (%)	P-value
Median age (range), years	59 (52–81)	67 (44–81)	0.089
Gender			0.475
Female	15 (24.1)	15 (33.3)
Male	49 (75.9)	31 (66.7)
Smoking history			0.963
Smoker	51 (51.7)	24 (52.4)
Non-smoker	13 (48.3)	22 (47.6)
ECOG PS			0.152
0–1	37 (58.6)	18 (38.1)
≥2	27 (41.4)	28 (61.9)
Pathological type			0.307
Adenocarcinoma	40 (62.1)	28 (61.9)
Squamous carcinoma	7 (10.3)	11 (23.8)
Other	17 (27.6)	7 (14.3)
Location			0.603
Central	20 (31)	18 (38.1)
Peripheral	44 (69)	28 (61.9)
Line of apatinib			0.352
Second line	26 (41.4)	13 (28.6)
Further line	38 (58.6)	33 (71.4)

Abbreviation: ECOG PS, Eastern Cooperative Oncology Group performance status.

Table 2 Treatment efficacy in patients with and without HTN

Clinical outcomes	All (n=110)	Normotensive (n=64)	Hypertensive (n=46)	P-value
Response rate				0.002
PR	18	4	14
SD	55	31	24
PD	37	29	8
PFS (months)	4.6	4.2	5.6	0.0027
OS (months)	8.2	7.8	9.9	0.005

Abbreviations: HTN, hypertension; PR, partial response; SD, stable disease; PD, progressive disease; PFS, progression-free survival; OS, overall survival.

Figure 1 Overall survival and progression-free survival by hypertension during apatinib treatment.

Notes: (A) PFS was compared between the two groups. (B) OS was compared between the two groups.

Table 3 Progression-free survival in univariate and multivariate analyses

Variables	Median (95% CI)	P-value
		Univariate	Multivariate
		Age (years)		0.037	0.089 (HR: 0.46, 95% CI: 0.21–1.12)
≥65	5.3 (3.59–7.01)
<65	3.8 (2.41–5.19)
Gender		0.422
Female	4.2 (3.25–5.15)
Male	4.6 (3.52–5.68)
Smoking history		0.178
Smoker	5 (3.55–6.45)
Non-smoker	4 (1.49–6.51)
ECOG performance status		0.029	0.017 (HR: 2.26, 95% CI: 1.16–4.39)
0–1	5.5 (4.26–6.74)
≥2	3.6 (2.47–4.73)
Pathological type		0.53
Adenocarcinoma	4.2 (3.56–4.84)
Non-adenocarcinoma	5 (3.78–6.22)
Line of apatinib		0.212
Second line	5.3 (4.34–6.26)
Further line	3.6 (3.1–4.1)
Location		0.515
Central	4 (2.23–5.77)
Peripheral	4.6 (3.76–5.44)
Apatinib-induced hypertension		0.0027	0.011 (HR: 0.413, 95% CI: 0.21–0.82)
Yes	5.6 (3.75–6.85)
No	4.2 (3.28–5.12)

Abbreviation: ECOG, Eastern Cooperative Oncology Group.

Table 4 Overall survival in univariate and multivariate analyses

Variables	Median (95% CI)	P-value
		Univariate	Multivariate
		Age (years)		0.045	0.092 (HR: 0.67, 95% CI: 0.12–1.22)
≥65	9.2 (8.25–10.15)
<65	6.6 (5.66–7.54)
Gender		0.704
Female	8.2 (7.62–8.78)
Male	8.2 (6.13–10.27)
Smoking history		0.999
Smoker	8.2 (6.05–10.35)
Non-smoker	8.8 (7.8–9.8)
ECOG performance status		0.119
0–1	9.4 (7.9–10.87)
≥2	8 (6.01–9.99)
Pathological type		0.364
Adenocarcinoma	8 (6.37–9.63)
Non-adenocarcinoma	9.4 (8.22–10.58)
Line of apatinib		0.123
Second line	9.4 (6.62–12.18)
Further line	8.2 (5.93–10.47)
Location		0.971
Central	8.2 (6.28–10.12)
Peripheral	8.5 (7.48–9.52)
Apatinib-induced hypertension		0.005	0.022 (HR: 0.45, 95% CI: 0.23–0.89)
Yes	9.9 (7.9–10.8)
No	7.8 (4.98–8.62)

Abbreviation: ECOG, Eastern Cooperative Oncology Group.

Figure 2 Landmark analysis of overall survival in patients with and without hypertension with landmark at 2 months.