Sorafenib Versus Lenvatinib-Based Sequential Systemic Therapy for Advanced Hepatocellular Carcinoma: A Real-World Analysis
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design and Patients
2.2. Statistical Analysis
3. Results
3.1. Baseline Characteristics
3.2. Sequences and Durations of Systemic Therapies
3.3. Sequential Treatment after First-Line Therapy with Sorafenib
3.4. Sequential Treatment after First-Line Therapy with Lenvatinib
3.5. Deterioration of Liver Function during Systemic Therapy
3.6. Survival
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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All Patients (n = 164) | Sorafenib as 1st Line (n = 93) | Lenvatinib as 1st Line (n = 71) | p Value (SOR vs. LEN) | |
---|---|---|---|---|
Age (years), median (IQR) | 68 (60.25–73) | 68 (62–72) | 66 (57–74) | 0.1 |
Male gender, n (%) | 140 (85) | 81 (87) | 59 (83) | 0.4 |
ECOG PS a | 0.04 | |||
0, n (%) | 92 (57) | 44 (48) | 48 (69) | |
1, n (%) | 64 (40) | 44 (48) | 20 (29) | |
2, n (%) | 4 (2) | 3 (3) | 1 (1) | |
3, n (%) | 1 (1) | 0 (0) | 1 (1) | |
Liver cirrhosis, n (%) | 123 (75) | 78 (84) | 45 (63) | 0.003 |
Underlying liver disease b | 0.0003 | |||
ASH, n (%) | 45 (29) | 36 (40) | 9 (13) | |
NASH, n (%) | 32 (20) | 17 (19) | 15 (22) | |
HCV, n (%) | 22 (14) | 14 (16) | 8 (12) | |
HBV, n (%) | 24 (15) | 10 (11) | 14 (21) | |
Autoimmune, n (%) | 3 (2) | 2 (2) | 1 (1) | |
Other or cryptogenic, n (%) | 32 (20) | 11 (12) | 21 (31) | |
Child-Pugh score b | 0.8 | |||
CPS A, n (%) | 132 (83.5) | 72 (83) | 60 (84.5) | |
CPS B, n (%) | 26 (16.5) | 15 (17) | 11 (15.5) | |
CPS C, n (%) | 0 | 0 | 0 | |
ALBI grade c | 0.1 | |||
1, n (%) | 65 (42) | 33 (39) | 32 (46) | |
2, n (%) | 85 (55) | 47 (55) | 38 (54) | |
3, n (%) | 5 (3) | 5 (6) | 0 (0) | |
ALBI score, median (IQR) c | −2.47 (−2.91 to −2.06) | −2.40 (−2.87 to −1.93) | −2.54 (−3.00 to −2.14) | 0.46 |
Albumin (g/dl), median (IQR) c | 3.9 (3.5–4.2) | 3.8 (3.4–4.2) | 4.0 (3.6–4.3) | 0.08 |
Bilirubin (mg/dl), median (IQR) b | 1.0 (0.6–1.6) | 1.0 (0.6–1.7) | 0.9 (0.6–1.5) | 0.5 |
Ascites, n (%) d | 40 (25) | 22 (24) | 18 (25) | 0.8 |
Refractory ascites, n (%) | 7 (4) | 3 (3) | 4 (6) | 1.0 |
Esophageal varices, n (%) a | 59 (37) | 35 (39) | 24 (34) | 0.4 |
Tumor stage e | 0.4 | |||
BCLC A, n (%) | 1 (1) | 0 (0) | 1 (1) | |
BCLC B, n (%) | 57 (35) | 35 (38) | 22 (32) | |
BCLC C, n (%) | 104 (63) | 57 (61) | 47 (67) | |
BCLC D, n (%) | 1 (1) | 1 (1) | 0 | |
Macrovascular invasion, n (%) | 49 (30) | 23 (25) | 26 (37) | 0.1 |
Extrahepatic tumor manifestations, n (%) | 80 (49) | 43 (46) | 37 (52) | 0.5 |
Prior locoregional therapy, n (%) | 106 (65) | 60 (65) | 46 (65) | 0.9 |
Resection, n (%) | 29 (18) | 16 (17) | 13 (18) | 0.9 |
TACE, n (%) | 55 (34) | 30 (32) | 25 (35) | 0.7 |
TARE, n (%) | 55 (34) | 32 (34) | 23 (32) | 0.8 |
Sorafenib (n = 88) | Lenvatinib (n = 66) | |
---|---|---|
1 therapy line | n = 40 | n = 32 |
Progress, n (%) | 9 (22.5) | 3 (9) |
Intolerance/Toxicity, n (%) | 18 (45) | 16 (50) |
Of that, liver function deterioration, n (%) | 13 (72) | 8 (50) |
Of that, other adverse events, n (%) | 5 (28) | 8 (50) |
Progress + intolerance, n (%) | 5 (12.5) | 3 (9) |
Death, n (%) | 6 (15) | 9 (28) |
Other, n (%) | 2 (5) | 1 (3) |
>1 therapy line | n = 48 | n = 34 |
Progress, n (%) | 25 (52) | 20 (59) |
Intolerance/Toxicity, n (%) | 17 (35) | 9 (26) |
Of that, liver function deterioration, n (%) | 6 (35) | 3 (33) |
Of that, other adverse events, n (%) | 11 (65) | 6 (67) |
Progress + intolerance, n (%) | 5 (10) | 4 (12) |
Other, n (%) | 1 (2) | 1 (3) |
Sorafenib as 1st-Line (n = 93) | Lenvatinib as 1st-Line (n = 71) | p Value | |
---|---|---|---|
First-line, days, median (IQR) | 99.5 (47–199.5), n = 88 | 120 (44–202.5), n = 65 | 0.3 |
Second-line, days, median (IQR) | 112 (57–175), n = 43 | 92 (37–201.5), n = 29 | 0.3 |
Third-line, days, median (IQR) | 87 (26–143.8), n = 12 | 109 (27.25–192.8), n = 12 | 0.4 |
Entire therapy, whole cohort, median (IQR) | 175.5 (80.5–333), n = 74 | 155 (61.5–395.5), n = 57 | 0.8 |
Entire therapy, patients with 2 or more systemic therapies, median (IQR) | 262 (182–434), n = 39 | 303 (195.5–581.5), n = 26 | 0.7 |
Liver Function at Beginning of First-Line Therapy with Sorafenib | Liver Function at the End of First-Line Therapy with Sorafenib | Liver Function at the End of the Entire Sequential Therapy If the Sequence Started with Sorafenib | ||||
---|---|---|---|---|---|---|
Child-Pugh Score | ||||||
n= 87 | n = 77 | n = 62 | ||||
A5, n (%) | 47 (54) | 72 (83) | 30 (39) | 37 (48) | 12 (19) | 16 (26) |
A6, n (%) | 25 (29) | 7 (9) | 4 (7) | |||
B7, n (%) | 9 (10) | 15 (17) | 13 (17) | 32 (42) | 9 (15) | 32 (52) |
B8, n (%) | 4 (5) | 9 (12) | 8 (13) | |||
B9, n (%) | 2 (2) | 10 (13) | 15 (24) | |||
C, n (%) | 0 | 0 | 8 (10) | 8 (10) | 14 (23) | 14 (23) |
ALBI Grade/ALBI Score | ||||||
n = 87 | n = 77 | n = 62 | ||||
1, n (%) | 35 (40) | 14 (18) | 4 (6.5) | |||
2, n (%) | 47 (54) | 35 (46) | 23 (37) | |||
3, n (%) | 5 (6) | 28 (36) | 35 (56.5) | |||
ALBI score, median (IQR) | −2.40 (−2.87 to −1.93) | −1.67 (−2.48 to −1.15) | −1.33 (−1.85 to −0.71) | |||
Liver Function at the Beginning of First-Line Therapy with Lenvatinib | Liver Function at the End of First-Line Therapy with Lenvatinib | Liver Function at the End of the Entire Sequential Therapy if the Sequence Started with Lenvatinib | ||||
Child-Pugh score | ||||||
n = 71 | n = 56 | n = 35 | ||||
A5, n (%) | 45 (63) | 60 (85) | 23 (41) | 34 (61) | 5 (14) | 11 (31) |
A6, n (%) | 15 (21) | 11 (20) | 6 (17) | |||
B7, n (%) | 6 (9) | 11 (15) | 6 (11) | 16 (29) | 7 (20) | 19 (54) |
B8, n (%) | 4 (6) | 6 (11) | 8 (23) | |||
B9, n (%) | 1 (1) | 4 (7) | 4 (11) | |||
C, n (%) | 0 | 0 | 6 (11) | 6 (11) | 5 (14) | 5 (14) |
ALBI grade/ALBI score | ||||||
n = 71 | n = 56 | n = 38 | ||||
1, n (%) | 33 (46.5) | 12 (21) | 4 (10.5) | |||
2, n (%) | 38 (56.3) | 27 (48) | 19 (50) | |||
3, n (%) | 0 | 17 (30) | 15 (39.5) | |||
ALBI score, median (IQR) | −2.54 (−3.00 to −2.14) | −1.89 (−2.46 to −1.21) | −1.74 (−2–23 to −0.88) |
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Leyh, C.; Ehmer, U.; Roessler, D.; Philipp, A.B.; Reiter, F.P.; Jeliazkova, P.; Jochheim, L.S.; Jeschke, M.; Hammig, J.; Ludwig, J.M.; et al. Sorafenib Versus Lenvatinib-Based Sequential Systemic Therapy for Advanced Hepatocellular Carcinoma: A Real-World Analysis. Cancers 2022, 14, 1975. https://doi.org/10.3390/cancers14081975
Leyh C, Ehmer U, Roessler D, Philipp AB, Reiter FP, Jeliazkova P, Jochheim LS, Jeschke M, Hammig J, Ludwig JM, et al. Sorafenib Versus Lenvatinib-Based Sequential Systemic Therapy for Advanced Hepatocellular Carcinoma: A Real-World Analysis. Cancers. 2022; 14(8):1975. https://doi.org/10.3390/cancers14081975
Chicago/Turabian StyleLeyh, Catherine, Ursula Ehmer, Daniel Roessler, Alexander B. Philipp, Florian P. Reiter, Petia Jeliazkova, Leonie S. Jochheim, Matthias Jeschke, Janina Hammig, Johannes M. Ludwig, and et al. 2022. "Sorafenib Versus Lenvatinib-Based Sequential Systemic Therapy for Advanced Hepatocellular Carcinoma: A Real-World Analysis" Cancers 14, no. 8: 1975. https://doi.org/10.3390/cancers14081975