Efficacy and Safety of Anlotinib Monotherapy as Third-Line Therapy for Elderly Patients with Non-Small Cell Lung Cancer: A Real-World Exploratory Study

Figures & data

Figure 1 Flow chart of the retrospective study of anlotinib monotherapy as third-line therapy for elderly patients with non-small cell lung cancer.

Table 1 Baseline Characteristics of the 83 Elderly Patients with Advanced NSCLC According to Hypertension Status

Characteristics	Total Patients (N=83, %)	Hypertension Status		χ^2	P
		Hypertension (N=41)	Non-Hypertension (N=42)
Age (years)
Median (range)	76 (65–87)	75 (65–85)	76 (65–87)	NA	0.615
Gender
Male	59 (71.1)	29 (70.7)	30 (71.4)	0.005	0.944
Female	24 (28.9)	12 (29.3)	12 (28.6)
Pathological stage
IIIb	7 (8.4)	3 (7.3)	4 (9.5)	0.131	0.718
IV	76 (91.6)	38 (92.7)	38 (90.5)
ECOG PS score
0–1	39 (47.0)	20 (48.8)	19 (45.2)	0.105	0.746
2	44 (53.0)	21 (51.2)	23 (54.8)
Smoking status
Nonsmoker/former smoker	65 (78.3)	31 (75.6)	34 (80.9)	0.349	0.555
Smoker	18 (21.7)	10 (24.4)	8 (19.1)
Histology
Adenocarcinoma	62 (74.7)	31 (75.6)	31 (73.8)	0.036	0.850
Squamous cell carcinoma	21 (25.3)	10 (24.4)	11 (26.2)
Number of metastases sites
≤3	52 (62.7)	26 (63.4)	26 (61.9)	0.020	0.887
>3	31 (37.3)	15 (36.6)	16 (38.1)
Driver gene mutation status^a
Positive	31 (37.3)	15 (36.6)	16 (38.1)	0.020	0.887
Negative	52 (62.7)	26 (63.4)	26 (61.9)
Lines of previous treatment
Second line	21 (25.3)	9 (22.0)	12 (28.6)	0.481	0.488
Subsequent line	62 (74.7)	32 (78.0)	30 (71.4)
History of targeted drug therapy
Yes	44 (53.0)	21 (51.2)	23 (54.8)	0.105	0.746
No	39 (47.0)	20 (48.8)	19 (45.2)
History of antiangiogenic TKI therapy
Yes	8 (9.6)	4 (9.8)	4 (9.5)	0.001	0.971
No	75 (90.4)	37 (90.2)	38 (90.5)
History of immunotherapy
Yes	19 (22.9)	9 (22.0)	10 (23.8)	0.041	0.840
No	64 (77.1)	32 (78.0)	32 (76.2)
Initial dosage of anlotinib (mg)
12	69 (83.1)	34 (82.9)	35 (83.3)	0.002	0.961
10	14 (16.9)	7 (17.1)	7 (16.7)

Note: ^aDriver gene mutation status was EGFR mutation or ALK or ROS1 rearrangement.

Abbreviations: NSCLC, non-small cell lung cancer; NA; not available; ECOG, Eastern Cooperative Oncology Group; PS, performance status; TKI, tyrosine kinase inhibitor.

Figure 2 Waterfall plot for the best percentage change in target lesion size of the 83 elderly patients with non-small cell lung cancer receiving anlotinib monotherapy according to hypertension status.

Figure 3 The CT scan results for the changes of target lesions in one elderly patient with non-small cell lung cancer before and after the treatment of anlotinib [follow-up date: December 5, 2018 (left) and March 4, 2019 (right)].

Table 2 Univariate Analysis for PFS of the 83 Elderly Patients with Advanced NSCLC According to Baseline Characteristics

Characteristics	N	Median PFS (Months)	95% CI	P
Age (Years)
<76	38	4.5	3.64–5.36	0.435
≥76	45	4.0	3.32–4.68
Gender
Male	59	3.9	3.21–4.59	0.318
Female	24	4.6	3.79–5.41
Pathological stage
IIIb	7	4.8	4.01–5.59	0.613
IV	76	4.2	3.49–4.91
ECOG PS score
0–1	39	5.0	1.13–8.87	0.009
2	44	3.1	1.79–4.41
Smoking status
Nonsmoker/former smoker	65	4.2	3.37–5.03	0.734
Smoker	18	4.2	3.41–4.99
Histology
Adenocarcinoma	62	4.4	3.73–5.07	0.411
Squamous cell carcinoma	21	4.0	3.19–4.81
Number of metastases sites
≤3	52	4.8	2.25–7.35	0.021
>3	31	3.6	2.09–5.11
Driver gene mutation status
Positive	31	4.4	3.62–5.18	0.616
Negative	52	4.2	3.54–4.86
Lines of previous treatment
Second line	21	4.2	3.58–4.82	0.519
Subsequent line	62	4.0	3.31–4.69
History of targeted drug therapy
Yes	44	4.4	3.59–5.21	0.439
No	39	3.9	3.08–4.72
History of antiangiogenic TKI therapy
Yes	8	3.9	3.27–4.53	0.562
No	75	4.2	3.41–4.99
History of immunotherapy
Yes	19	4.8	4.04–5.56	0.313
No	64	4.0	3.18–4.82
Initial dosage of anlotinib (mg)
12	69	4.5	3.77–5.23	0.432
10	14	4.0	3.21–4.79

Abbreviations: NSCLC, non-small cell lung cancer; NA; not available; ECOG, Eastern Cooperative Oncology Group; PS, performance status; TKI, tyrosine kinase inhibitor; CI, confidence interval.

Figure 4 Progression-fee survival (A) and Overall Survival (B) of the 83 elderly patients with treatment refractory non-small cell lung cancer receiving anlotinib monotherapy.

Table 3 Safety Profile of the 83 Elderly Patients with Advanced NSCLC Receiving Anlotinib Monotherapy

Adverse Reactions	Total (N, %)	Grade 1–2 (N, %)	Grade ≥3 (N, %)
Hypertension	41 (49.4)	26 (31.3)	15 (18.1)
Fatigue	38 (45.8)	33 (39.8)	5 (6.0)
Hand-foot syndrome	33 (39.8)	27 (32.5)	6 (7.2)
Diarrhea	28 (33.7)	25 (30.1)	3 (3.6)
Loss of weight	26 (31.3)	22 (26.5)	4 (4.8)
Decreased appetite	18 (21.7)	17 (20.5)	1 (1.2)
Hematological toxicity	15 (18.1)	13 (15.7)	2 (2.4)
Hypertriglyceridemia	11 (13.3)	10 (12.1)	1 (1.2)
AST/ALT elevation	8 (9.6)	7 (8.4)	1 (1.2)
Hemoptysis	5 (6.0)	4 (4.8)	1 (1.2)

Abbreviations: NSCLC, non-small cell lung cancer; AST, aspartate amino transferase; ALT, alanine aminotransferase.

Figure 5 Progression-free survival of the 83 elderly patients with treatment refractory non-small cell lung cancer according to hypertension status.

Table 4 Multivariate Cox Analysis for PFS According to Baseline Characteristics and Hypertension Status

Characteristics	HR	95% CI	P
ECOG PS score
0–1 vs 2	0.63	0.29–0.89	0.015
Number of metastases sites
≤3 vs >3	0.75	0.45–0.94	0.035
Hypertension status
Hypertension vs non-hypertension	0.69	0.42–0.91	0.021

Abbreviations: ECOG, Eastern Cooperative Oncology Group; PS, performance status; HR, hazard ratio; CI, confidence interval.