Association Between PDL1 Genetic Variation and Efficacy of Apatinib Monotherapy in Patients with Previously Treated Advanced NSCLC: A Real-World Retrospective Study

Figures & data

Figure 1 Flowchart of the study.

Table 1 Baseline characteristics based on PDL1 rs2297136 genotype status

	Total Patients (n=148, %)	TT genotype (n=103)	TC/CC genotype (n=45)	P
Age (years)
Median (range)	58 (28–79)	58 (28–75)	59 (30–79)	0.431
Sex
Male	96 (64.86)	67 (65.05)	29 (64.44)	0.944
Female	52 (35.14)	36 (34.95)	16 (35.56)
Pathological stage
IIIB	8 (5.41)	5 (4.85)	3 (6.67)	0.654
IV	140 (94.59)	98 (95.15)	42 (93.33)
ECOG score
0	39 (26.35)	27 (26.21)	12 (26.67)	0.954
1–2	109 (73.65)	76 (73.79)	33 (73.33)
Smoking status
Nonsmoker/former smoker	107 (72.30)	74 (71.84)	33 (73.33)	0.852
Smoker	41 (27.70)	29 (28.16)	12 (26.67)
Histology
Adenocarcinoma	114 (77.03)	80 (77.67)	34 (75.56)	0.960
Squamous cell carcinoma	28 (18.92)	19 (18.45)	9 (20.00)
Other type	6 (4.05)	4 (3.88)	2 (4.44)
Number of metastasis sites
≤3	92 (62.16)	64 (62.14)	28 (62.22)	0.992
>3	56 (37.84)	39 (37.86)	17 (37.78)
Driver-gene mutation status^a
Positive	56 (37.84)	39 (37.86)	17 (37.78)	992
Negative	92 (62.16)	64 (62.14)	28 (62.22)
Previous systemic treatment
Second line	43 (29.05)	28 (27.18)	15 (33.33)	0.449
Further line	105 (70.95)	75 (72.82)	30 (66.67)
History of targeted drug therapy
Yes	92 (62.16)	62 (60.19)	30 (66.67)	0.455
No	56 (37.84)	41 (39.81)	15 (33.33)
History of antivascular TKI therapy
Yes	10 (6.76)	7 (6.80)	3 (6.67)	0.977
No	138 (93.24)	96 (93.20)	42 (93.33)
History of PD1/PDL1-inhibitor therapy
Yes	11 (7.4)	7 (6.8)	4 (8.9)	0.655
No	137 (92.6)	96 (93.2)	41 (91.1)
Initial dosage of apatinib (mg)
500	97 (65.54)	67 (65.05)	30 (66.67)	0.849
750	51 (34.46)	36 (34.95)	15 (33.33)

Note: ^aEGFR mutation or ALK or ROS1 rearrangements.

Abbreviations: NSCLC, non–small cell lung cancer; ECOG, Eastern Cooperative Oncology Group; TKI, tyrosine-kinase inhibitor.

Figure 2 Waterfall plot of best change (reductions in sum of target-lesion diameters) from baseline.

Figure 3 Progression-free survival and overall survival.

Table 2 Univariate analysis of progression-free survival based on baseline characteristics

	Patients, n	Median PFS	95% CI	P
Age (years)
<58	71	4.0	3.35–4.65	0.513
≥58	77	3.6	2.95–4.25
Sex
Male	96	3.5	3.11–3.89	0.311
Female	52	4.1	3.05–5.15
Pathological stage
IIIB	8	4.2	3.32–4.93	0.635
IV	140	3.7	3.10–4.22
ECOG score
0	39	4.9	3.88–5.87	0.018
1–2	109	3.2	2.85–3.55
Smoking status
Nonsmoker/former smoker	107	4.1	3.25–4.95	0.416
Smoker	41	3.3	2.81–3.79
Histology
Adenocarcinoma	114	3.9	3.15–4.65	0.752
Squamous-cell carcinoma	28	3.6	2.88–4.12
Number of metastasis sites
≤3	92	4.5	3.73–5.27	0.025
>3	56	3.2	2.44–3.82
Driver-gene mutation status ^a
Positive	56	3.9	3.15–4.65	0.554
Negative	92	3.7	2.98–4.42
Previous systemic treatment
Second line	43	4.2	3.34–5.06	0.215
Further line	105	3.6	3.11–4.09
History of targeted drug therapy
Yes	92	3.8	3.01–4.59	0.653
No	56	3.7	2.98–4.42
History of antivascular TKI therapy
Yes	10	3.5	2.86–4.14	0.718
No	138	3.9	3.24–4.56
Initial dosage of apatinib (mg)
500	97	3.7	3.18–4.22	0.616
750	51	3.9	3.21–4.59

Note: ^aThe driver gene were EGFR mutation or ALK or ROS1 rearrangements

Abbreviations: NSCLC, non-small cell lung cancer; ECOG, eastern cooperative oncology group; TKI, tyrosine kinase inhibitor; PFS, progression-free survival; CI, confidence interval.

Table 3 Multivariate Cox regression analysis for PFS based on baseline characteristics and rs2297136 polymorphism status

	OR (95% CI)	df	P
ECOG score
1–2 vs 0	1.52 (1.09–2.02)	1	0.027
Number of metastasis sites
>3 vs ≤3	1.39 (1.05–1.73)	1	0.039
PDL1 rs2297136 status
TC/CC vs TT	1.47 (1.11–1.83)	1	0.011

Figure 4 Progression-free survival based on PDL1 rs2297136 genotype status.

Figure 5 Overall survival based on PDL1 rs2297136 genotype status.

Table 4 Correlation analysis between PDL1 rs2297136 polymorphism and safety profile of apatinib administration

Adverse events	Grade 1–2	Grade 3–4	Total, (%)	rs2297136 genotype status		P
				TT (n=103)	TC/CC (n=45)
Hypertension	50 (33.78)	17 (11.49)	67 (45.27)	46 (44.66)	21 (46.67)	0.822
Dermal toxicity	51 (34.46)	11 (7.43)	62 (41.89)	44 (42.72)	18 (40.00)	0.758
Fatigue	51 (34.46)	4 (2.70)	55 (37.16)	40 (38.83)	15 (33.33)	0.524
Oral toxicity	45 (30.41)	2 (1.35)	47 (31.76)	33 (32.04)	14 (31.11)	0.911
Appetite decreased	43 (29.05)	3 (2.03)	46 (31.08)	34 (33.01)	12 (26.67)	0.443
Diarrhea	32 (21.62)	4 (2.70)	36 (24.32)	27 (26.21)	9 (20.00)	0.418
Nausea and vomiting	26 (17.57)	0	26 (17.57)	19 (18.36)	7 (15.56)	0.671
Hematologic toxicity	15 (10.14)	2 (1.35)	17 (11.49)	10 (9.71)	7 (15.56)	0.305

Figure 6 Relative expression level of PDL1 mRNA based on PDL1 rs2297136 genotype status.

Figure 7 Progression-free survival of the 68 specimens from patients based on PDL1 mRNA–expression status.