Atezolizumab/Bevacizumab vs. Lenvatinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Real-World, Multi-Center Study
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Treatment Regimens
2.2. Assessment of Clinical Outcomes
2.3. Statistical Analysis
3. Results
3.1. Baseline Characteristics
3.2. Treatment Responses
3.3. OS and PFS
3.4. PS-Matched and IPTW Analyses of Clinical Efficacy
3.5. Subsequent Therapy
3.6. Safety
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variable | All (n = 232) | LENV Group (n = 146) | ATE/BEV Group (n = 86) | p-Value |
---|---|---|---|---|
Age, years | 62 (56–62) | 62 (55–70) | 62 (56–71) | 0.564 |
Male | 194 (83.6) | 124 (84.9) | 70 (81.4) | 0.582 |
ECOG PS | ||||
0 | 141 (60.8) | 105 (71.9) | 36 (41.9) | <0.001 |
1/2 | 91 (39.2) | 41 (28.1) | 50 (58.2) | |
Etiology | 0.582 | |||
HBV | 152 (65.5) | 90 (61.6) | 62 (72.1) | |
HCV | 22 (9.5) | 19 (13.0) | 3 (2.5) | |
Alcohol | 23 (9.9) | 12 (8.2) | 11 (12.8) | |
Others | 35 (15.1) | 25 (17.1) | 10 (11.7) | |
BCLC stage | ||||
B | 32 (13.8) | 14 (9.6) | 18 (20.9) | 0.001 |
C | 200 (86.2) | 132 (90.4) | 68 (79.1) | |
Child-Pugh Class | ||||
A | 209 (90.0) | 127 (87.0) | 82 (95.4) | 0.169 |
B | 23 (10.0) | 19 (13.0) | 4 (4.7) | |
Number of intraheptic tumors | ||||
0 | 20 (8.6) | 14 (9.6) | 6 (7.0) | 0.001 |
1 | 55 (23.7) | 34 (23.3) | 21 (24.4) | |
2 | 41 (17.7) | 14 (9.6) | 27 (31.4) | |
3 | 18 (7.8) | 12 (8.2) | 6 (7.0) | |
>3 | 98 (42.2) | 72 (49.3) | 26 (30.2) | |
Maximal size of intraheptic tumor, cm | 6.0 (2.8–11.3) | 7.0 (3.0–11.6) | 4.9 (2.2–10.0) | 0.197 |
Extrahepatic metastasis | 128 (55.1) | 91 (62.3) | 37 (43.0) | 0.006 |
Macrovascular invasion | 119 (51.3) | 76 (52.1) | 43 (50.0) | 0.787 |
Platelet count > 100 × 103/uL | 172 (74.1) | 105 (71.9) | 67 (77.9) | 0.314 |
AFP, ng/mL | 159 (12–2698) | 185 (12–3138) | 91 (12–2383) | 0.303 |
PIVKA-II, mAU/mL | 934 (58–10,218) | 1899 (75–12,965) | 223 (38–4872) | 0.540 |
Previous treatment | 153 (65.9) | 93 (63.7) | 60 (69.8) | 0.391 |
Surgery | 42 (18.1) | 19 (13.0) | 23 (26.7) | 0.013 |
Transarterial therapy | 122 (52.6) | 77 (52.7) | 45 (52.3) | 1.000 |
Radioablation therapy | 28 (12.1) | 19 (13.0) | 9 (10.5) | 0.678 |
Radiation therapy | 60 (25.8) | 40 (27.4) | 20 (23.3) | 0.298 |
Presence of varices | 147 (63.4) | 87 (59.6) | 60 (69.8) | 0.295 |
Treated varices at baseline | 48 (20.7) | 28 (19.2) | 20 (23.3) | 0.195 |
Response | RECIST 1.1 | Modified RECIST | ||||
---|---|---|---|---|---|---|
LENV Group | ATE/BEV Group | p-Value | LENV Group | ATE/BEV Group | p-Value | |
Complete response | 2 (1.4) | 3 (3.5) | 0.745 | 2 (1.4) | 3 (3.5) | 0.742 |
Partial response | 44 (30.1) | 25 (29.1) | 47 (32.2) | 27 (31.4) | ||
Stable disease | 66 (45.2) | 37 (43.0) | 63 (43.2) | 35 (40.7) | ||
Progressive disease | 34 (23.3) | 21 (24.4) | 34 (23.3) | 21 (24.4) | ||
Objective response rate | 31.5 | 32.6 | 0.868 | 33.6 | 34.9 | 0.485 |
Disease control rate | 76.7 | 75.6 | 0.760 | 76.8 | 75.6 | 0.682 |
Clinical Responses and Survival Outcomes | LENV Group | ATE/BEV Group | p-Value |
---|---|---|---|
Entire cohort, unadjusted | n = 146 | n = 86 | |
Objective response rate, % | 31.5 | 32.6 | 0.704 |
Overall survival, months (95% CI) | 12.8 (6.7–18.9) | N/A | 0.357 |
Progression-free survival, months (95% CI) | 6.0 (5.2–6.7) | 5.7 (2.1–9.3) | 0.738 |
Entire cohort, PS-matched | n = 78 | n = 78 | |
Objective response rate, % | 37.2 | 32.0 | 0.501 |
Overall survival, month (95% CI) | 19.9 (9.8–19.9) | N/A | 0.897 |
Progression-free survival, months (95% CI) | 7.3 (5.7–9.4) | 5.7 (3.8–10.5) | 0.391 |
Entire cohort, IPTW analysis | n = 136 | n = 136 | |
Objective response rate, % | 32.4 | 31.4 | 0.861 |
Overall survival, months (95% CI) | 19.9 (11.1–N/A) | N/A | 0.508 |
Progression-free survival, months (95% CI) | 6.0 (5.0–7.3) | 4.3 (3.0–8.0) | 0.468 |
LENV Group (n = 146) | ATE/BEV Group (n = 86) | |||
---|---|---|---|---|
Adverse Events | Any Grade n (%) | Grade 3 or 4 n (%) | Any Grade n (%) | Grade 3 or 4 n (%) |
Hypertension | 22 (15.1) | 4 (2.7) | 36 (41.9) | 5 (5.8) |
AST elevation | 35 (24.0) | 1 (0.7) | 32 (37.2) | 7 (8.1) |
Thrombocytopenia | 22 (15.1) | 0 | 31 (36.0) | 3 (3.5) |
Fatigue | 36 (24.7) | 3 (2.1) | 31 (36.0) | 0 |
Anemia | 8 (5.5) | 1 (0.7) | 22 (25.6) | 1 (1.2) |
Anorexia | 42 (28.8) | 10 (6.8) | 20 (23.3) | 0 |
ALT elevation | 29 (19.9) | 0 | 19 (22.1) | 2 (2.3) |
Proteinuria | 25 (17.1) | 4 (2.7) | 19 (22.1) | 1 (1.2) |
Total bilirubin elevation | 22 (15.1) | 1 (0.7) | 15 (17.4) | 4 (4.7) |
Nausea | 14 (9.6) | 0 | 11 (12.8) | 0 |
Rash | 2 (1.4) | 0 | 10 (11.6) | 2 (2.3) |
Neutropenia | 12 (8.2) | 0 | 10 (11.6) | 2 (2.3) |
Pruritus | 4 (2.8) | 0 | 7 (8.1) | 1 (1.2) |
Gastrointestinal bleeding | 4 (2.7) | 4 (2.7) | 5 (5.8) | 3 (3.5) |
Vomiting | 6 (4.1) | 0 | 4 (4.7) | 0 |
Gastrointestinal perforation | 1 (0.7) | 1 (0.7) | 3 (3.5) | 3 (3.5) |
Diarrhea | 20 (13.7) | 4 (2.7) | 3 (3.5) | 0 |
Hypothyroidism | 12 (8.2) | 0 | 2 (2.3) | 0 |
Intracranial hemorrhage | 0 | 0 | 1 (1.2) | 1 (1.2) |
Pulmonary embolism | 1 (0.7) | 1 (0.7) | 1 (1.2) | 1 (1.2) |
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Kim, B.K.; Cheon, J.; Kim, H.; Kang, B.; Ha, Y.; Kim, D.Y.; Hwang, S.G.; Chon, Y.E.; Chon, H.J. Atezolizumab/Bevacizumab vs. Lenvatinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Real-World, Multi-Center Study. Cancers 2022, 14, 1747. https://doi.org/10.3390/cancers14071747
Kim BK, Cheon J, Kim H, Kang B, Ha Y, Kim DY, Hwang SG, Chon YE, Chon HJ. Atezolizumab/Bevacizumab vs. Lenvatinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Real-World, Multi-Center Study. Cancers. 2022; 14(7):1747. https://doi.org/10.3390/cancers14071747
Chicago/Turabian StyleKim, Beom Kyung, Jaekyung Cheon, Hyeyeong Kim, Beodeul Kang, Yeonjung Ha, Do Young Kim, Seong Gyu Hwang, Young Eun Chon, and Hong Jae Chon. 2022. "Atezolizumab/Bevacizumab vs. Lenvatinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Real-World, Multi-Center Study" Cancers 14, no. 7: 1747. https://doi.org/10.3390/cancers14071747