Outcomes of the Sequential Treatment of Unresectable Hepatocellular Carcinoma Using Lenvatinib

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Figure legends

Figure 1. Overall survival of all patients after lenvatinib administration.

Figure 2. Overall survival rates according to the radiological evaluations

performed using the modified RECIST. Survival was assessed as the “disease

control rate” or “progressive disease” at each of the following timepoints. (A)

One month after lenvatinib administration; (B) 2–3 months after lenvatinib

administration; and (C) 3–4 months after lenvatinib administration. DCR:

Disease control rate; PD: progressive disease.

Figure 3. Comparison of the overall survival rates among the timepoints when

progressive disease was first diagnosed. (A) 1 month, 2–3 months, and 3–4

months after lenvatinib administration. (B) 2–3 months and 3–4 months after

lenvatinib administration.

Figure 4. Overall survival rates according to the cutoff α-fetoprotein ratio (i.e.,

the ratio of the α-fetoprotein level at 3 months after lenvatinib administration to

the pretreatment α-fetoprotein level).

Figure 1

Survival rate

MST; 16.4 month

1-year survival rates; 61.8%

2-year survival rates; 37.8%

Time after lenvatinib administration (months)

Number at risk

85

68

49

29

18

Figure 2

(a)

(b)

(c)

DCR

PD

Survival rate

DCR

PD

P < 0.001

DCR

PD

P = 0.018

Time after lenvatinib administration (months)

P = 0.034

Time after lenvatinib administration (months)

Time after lenvatinib administration (months)

Number at risk

Group: DCR

49

43

35

22

15

43

42

35

22

16

35

35

30

19

14

Group: PD

10

Figure 3

(a)

(b)

Survival rate

1 month

2-3 months

3-4 months

2-3 months

3-4 months

P < 0.001

P = 0.653

Time after lenvatinib administration (months)

Time after lenvatinib administration (months)

Number at risk

Group: 1 month

Group: 2-3 months

10

10

Group: 3-4 months

Figure 4

Survival rate

above the cut off value

below the cut off value

P = 0.002

Time after lenvatinib administration (months)

Number at risk

Group: above the cut off value

16

13

Group: below the cut off value

45

45

37

25

16

Table I. Patient characteristics.

Characteristics

All patients

Age, years, median (range)

71.5 (34-86)

Sex, n (%)

Male

68 (80)

Female

17 (20)

ECOG-PS

0:1:2

61 : 22 : 2

Original disease, n (%)

HBV and/or HCV

52 (61.2)

Others

33 (38.8)

Child-Pugh classification, n (%)

64 (75.3)

21 (24.7)

mALBI grade, n (%)

1/2a

44 (51.8)

2b/3

41 (48.2)

AFP, ng/dl, median (range)

PIVKA-II, mU/l, median (range)

87 (2-554601)

193 (13-152517)

Pathological differentiation degree, n (%)

Well and moderate

44 (51.8)

Poor, combine and sarcomatoid

14 (16.5)

None or unknown

27 (31.7)

Maximal tumor size, cm, median (range)

3.2 (0.5-18)

Region of tumor, n (%)

Intrahepatic only

35 (41.2)

Extrahepatic only

20 (23.5)

Both

30 (35.3)

BCLC classification, n (%)

20 (23.5)

65 (76.5)

ECOG-PS: Eastern cooperative oncology group performance status; HBV:

hepatitis B virus; HCV: hepatitis C virus; mALBI: modified albumin-bilirubin; AFP:

α-fetoprotein; PIVKA-II: protein induced by vitamin K absence or antagonist II;

BCLC: Barcelona Clinic Liver Cancer.

Table II. Radiological evaluations performed at each timepoint after lenvatinib administration.

After 1 month

(n = 52)

After 2-3 months

(n = 42)

After 3-4 months

(n = 41)

CR, n (%)

8 (15.4)

6 (14.2)

7 (17.1)

PR, n (%)

13 (25.0)

13 (31.0)

9 (22.0)

SD, n (%)

28 (53.8)

13 (31.0)

11 (26.8)

PD, n (%)

3 (5.8)

10 (23.8)

14 (34.1)

ORR (CR+PR), n (%)

21 (40.4)

19 (45.2)

16 (39.1)

DCR (CR+PR+SD), n

(%)

49 (94.2)

32 (76.2)

27 (65.9)

CR: Complete response; PR: partial response; SD: stable disease; PD: progressive disease;

ORR: overall response rate; DCR: disease control rate.

Table III. Comparison of demographic data based on the cutoff value of the α-fetoprotein (AFP)

ratio.

AFP ratio ≤ 1.36075

AFP ratio > 1.36075

p-Value

(n = 45)

(n = 16)

Age (years)*

69.9 (9.4)

70.9 (9.6)

0.7179

Sex ratio

0.0370

Male

37

10

Female

Original disease, n (%)

0.3130

HBV and/or HCV

29

Others

16

mALBI grade

0.0618

1/2a

29

2b/3

16

10

BCLC stage

0.5994

Stage B

11

Stage C

34

11

Treatment line

0.8216

First line

35

12

Second or later line

10

Macroscopic vascular invasion

0.3832

Yes

10

No

35

14

Distant metastases

0.3955

Yes

28

No

17

Intrahepatic maximal tumor size

0.6366

> 5 cm

11

≤ 5 cm

34

13

Values in parentheses are percentages unless indicated otherwise; *values are mean (standard

deviation).

AFP: α-fetoprotein; HBV: hepatitis B virus; HCV: hepatitis C virus; mALBI: modified albumin-bilirubin;

BCLC: Barcelona Clinic Liver Cancer.

Table IV. Adverse events.

All cases

(n = 85)

mALBI grade

1/2a

(n = 44)

mALBI grade

2b/3

(n = 41)

p-Value

Any grades, n (%)

84 (98.8)

43 (97.7)

41 (100)

0.332

Grade 3/4, n (%)

40 (47.1)

17 (38.6)

23 (56.1)

0.107

mALBI: Modified albumin-bilirubin.

...