Efficacy and Effect on Liver Functional Reserve of Atezolizumab and Bevacizumab for Unresectable Hepatocellular Carcinoma in Patients Who Do Not Meet Eligibility Criteria of IMbrave150
Abstract
:Simple Summary
Abstract
1. Introduction
2. Methods
2.1. Patients and Study Design
2.2. Treatment Protocol
2.3. Evaluation of Liver Functional Reserve during Treatment
2.4. Statistical Analysis
3. Results
3.1. Overview of Patient Characteristics According to Eligibility Criteria of IMbrave150
3.2. Progression-Free Survival and Associated Factors in Patients Who Did or Did Not Meet the IMbrave150 Eligibility Criteria
Treatment Response
3.3. Changes in ALBI Score, mALBI Grade, and the Rate of Treatment Interruption
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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Clinical Characteristics | Overall Cohort (n = 115) | Met the IMbrave150 Criteria (n = 43) | Did Not Meet the IMbrave150 Criteria (n = 72) | p-Value |
---|---|---|---|---|
Age, years (range) | 72 (31–89) | 73 (31–84) | 72 (37–89) | 0.744 |
Sex | ||||
Male/Female | 95 (82.6%)/20 (17.4%) | 38 (88.4%)/5 (11.6%) | 57 (79.2%)/15 (20.8%) | 0.309 |
Etiology | ||||
HBV | 35 (30.4%) | 11 (25.6%) | 24 (33.3%) | 0.411 |
HCV | 21 (18.3%) | 10 (23.3%) | 11 (15.3%) | 0.324 |
Non-viral | 59 (51.3%) | 22 (51.2%) | 37 (51.4%) | 1.000 |
ECOG PS | ||||
0/1–2 | 92 (80.0%)/23 (20.0%) | 39 (90.7%)/4 (9.3%) | 53 (73.6%)/19 (26.4%) | 0.031 |
BMI, kg/m2 | 23.6 (15.9–37.7) | 24.0 (18.7–37.7) | 23.3 (15.9–33.0) | 0.152 |
Proteinuria | ||||
0–1+/2+ | 98 (85.2%)/8 (7.0%) | 41 (89.1%)/0 (0.0%) | 57 (79.2%)/8 (11.1%) | 0.022 |
White blood cell, mm3 | 4920 (1970–12780) | 5300 (2950–12,780) | 4900 (1970–11,800) | 0.043 |
Neutrophil count, mm3 | 3203 (1185–9971) | 3380 (1503–9204) | 2978 (1185–9971) | 0.098 |
Lymphocyte count, mm3 | 1168 (140–2881) | 1207 (559–2657) | 1100 (140–2881) | 0.056 |
Neutrophil/Lymphocyte ratio | 2.70 (0.83–18.68) | 3.04 (0.83–7.92) | 2.57 (0.98–18.68) | 0.967 |
Platelet, ×109/L | 162 (36–586) | 154 (77–558) | 167 (36–586) | 0.773 |
Prothrombin time, % | 92.9 (35.3–150.0) | 90.0 (42.6–116.9) | 94.6 (35.3–150.0) | 0.317 |
NH3, µg/dL | 42 (8–136) | 42 (17–116) | 42 (8–136) | 0.538 |
Albumin, g/dL | 3.7 (2.6–4.8) | 3.8 (2.9–4.8) | 3.7 (2.6–4.8) | 0.030 |
Total bilirubin, mg/dL | 0.8 (0.2–3.8) | 0.8 (0.2–2.9) | 0.8 (0.3–3.8) | 0.979 |
mALBI grade | ||||
½ | 38 (33.0%)/77 (67.0%) | 17 (39.5%)/26 (60.5%) | 21 (29.2%)/51 (70.8%) | 0.307 |
1 | 38 (33.0%) | 17 (39.5%) | 21 (29.2%) | 0.307 |
2a | 37 (32.2%) | 15 (34.8%) | 22 (30.6%) | 0.683 |
2b | 40 (34.8%) | 11 (25.6%) | 29 (40.3%) | 0.156 |
AST, IU/L | 42 (14–672) | 35 (16–128) | 47 (14–672) | 0.164 |
ALT, IU/L | 28 (7–278) | 25 (8–122) | 33 (7–289) | 0.256 |
Child-Pugh Grade | ||||
A/B | 106 (92.2%)/9 (7.8%) | 43 (100.0%)/0 (0.0%) | 63 (87.5%)/9 (12.5%) | 0.025 |
Child-Pugh Score | ||||
5 | 62 (53.9%) | 24 (55.8%) | 38 (52.8%) | 0.847 |
6 | 44 (38.3%) | 19 (44.9%) | 25 (34.7%) | 0.329 |
7 | 6 (5.2%) | 0 (0.0%) | 6 (8.3%) | 0.082 |
8 | 3 (2.6%) | 0 (0.0%) | 3 (4.2%) | 0.292 |
AFP, ng/mL * | 74.2 (0.8–1,450,000.0) | 51.6 (0.8–591,315.4) | 77.2 (1.1–14,500,000.0) | 0.817 |
AFP > 400 | 40 (34.8%) | 15 (34.9%) | 25 (34.7%) | 1.000 |
DCP, mAU/mL * | 924 (11–245,000) | 509 (21–213,066) | 1787 (11–245,000) | 0.035 |
Maximum intrahepatic tumor size, mm | 36 (0–220) | 30 (0–167) | 38 (0–220) | 0.307 |
More than 50% liver involvement | 16 (17.7%) | 4 (9.3%) | 12 (16.7%) | 0.405 |
Diffuse type | 15 (15.6%) | 5 (11.6%) | 10 (13.9%) | 0.784 |
Number of intrahepatic tumors | ||||
None | 14 (12.2%) | 5 (11.6%) | 9 (12.5%) | 1.000 |
1 | 11 (9.6%) | 5 (11.6%) | 6 (8.3%) | 0.745 |
Multiple | 90 (78.3%) | 33 (76.7%) | 57 (79.2%) | 0.817 |
BCLC stage | ||||
B/C | 35 (30.4%)/80 (69.6%) | 13 (30.2%)/30 (69.8%) | 22 (30.6%)/50 (69.4%) | 1.000 |
Up-to-7 in/out | 30 (26.1%)/85 (73.9%) | 10 (23.3%)/33 (76.7%) | 20 (27.8%)/52 (72.2%) | 0.665 |
Positive for Vp | 23 (20.0%) | 11 (25.6%) | 12 (16.7%) | 0.335 |
Vp4 | 4 (3.5%) | 2 (4.7%) | 2 (2.8%) | 0.629 |
Positive for Vv | 5 (4.3%) | 1 (2.3%) | 4 (5.6%) | 0.649 |
Positive for bile duct invasion | 4 (3.5%) | 1 (2.3%) | 3 (4.2%) | 1.000 |
Positive for LN metastasis | 20 (17.4%) | 7 (16.8%) | 13 (18.1%) | 1.000 |
Positive for EHM | 46 (40.0%) | 17 (39.5%) | 29 (40.3%) | 1.000 |
History of varices treatment | 8 (7.0%) | 1 (2.3%) | 7 (9.7%) | 0.255 |
History of hypertension | 69 (60.0%) | 27 (62.8%) | 42 (58.3%) | 0.697 |
Naïve/recurrence | 14 (20.9%)/91 (79.1%) | 15 (34.9%)/28 (65.1%) | 9 (12.5%)/63 (87.5%) | 0.008 |
History of operation | 59 (51.3%) | 21 (48.8%) | 38 (52.8%) | 0.707 |
History of RFA | 41 (35.7%) | 14 (32.6%) | 25 (34.7%) | 0.842 |
History of TACE | 58 (50.4%) | 14 (32.6%) | 44 (61.1%) | 0.004 |
1st line systemic chemotherapy | 55 (47.8%) | 43 (100.0%) | 12 (16.7%) | <0.001 |
2nd line | 41 (35.7%) | 0 (0.0%) | 41 (56.9%) | |
3rd line | 19 (16.5%) | 0 (0.0%) | 19 (26.4%) | |
History of TKI | 60 (52.2%) | 0 (0.0%) | 60 (83.3%) | |
Sorafenib | 19 (16.5%) | 0 (0.0%) | 19 (27.5%) | |
Regorafenib | 8 (7.0%) | 0 (0.0%) | 8 (11.1%) | |
Lenvatinib | 59 (51.3%) | 0 (0.0%) | 59 (81.9%) | |
Observation period, months * | 6.8 (0.1–15.4) | 5.6 (0.1–14.9) | 7.2 (0.3–15.4) | 0.140 |
RECIST v1.1 | mRECIST | |||
---|---|---|---|---|
6 weeks | Best response | 6 weeks | Best response | |
CR, n (%) | 0 (0.0) | 3 (2.9) | 2 (1.9) | 9 (8.7) |
PR, n (%) | 9 (8.7) | 17 (16.3) | 18 (17.3) | 20 (19.2) |
SD, n (%) | 74 (71.2) | 63 (60.6) | 61 (58.7) | 51 (49.0) |
PD, n (%) | 18 (17.3) | 21 (20.2) | 12 (12.5) | 16 (15.4) |
NE, n (%) | 3 (2.9) | 0 (0.0) | 10 (9.6) | 8 (7.7) |
ORR, n (%) | 9 (8.7) | 20 (19.2) | 20 (19.2) | 29 (27.9) |
DCR, n (%) | 83 (79.8) | 83 (79.8) | 81 (77.9) | 80 (76.9) |
RECIST v1.1 | mRECIST | |||||
---|---|---|---|---|---|---|
IMbrave150 in (n = 38) | IMbrave150 out (n = 66) | p-Value | IMbrave150 in (n = 38) | IMbrave150 out (n = 66) | p-Value | |
ORR (%) | 18.4% | 19.7% | 1.000 | 29.0% | 27.3% | 1.000 |
DCR (%) | 81.6% | 78.8% | 0.804 | 73.7% | 78.8% | 0.631 |
1st line (n = 48) | 2nd line- (n = 56) | p-value | 1st line (n = 48) | 2nd line- (n = 56) | p-value | |
ORR (%) | 18.8% | 19.6% | 1.000 | 31.3% | 25.0% | 0.517 |
DCR (%) | 81.3% | 78.6% | 0.809 | 75.0% | 78.6% | 0.816 |
Child-Pugh A (n = 96) | Child-Pugh B (n = 8) | p-value | Child-Pugh A (n = 96) | Child-Pugh B (n = 8) | p-value | |
ORR (%) | 20.8% | 0.0% | 0.349 | 28.1% | 25.0% | 1.000 |
DCR (%) | 79.2% | 87.5% | 1.000 | 77.1% | 75.0% | 1.000 |
Proteinuria 0-1+ (n = 91) | Proteinuria 2+ (n = 7) | p-value | Proteinuria 0-1+ (n = 91) | Proteinuria 2+ (n = 7) | p-value | |
ORR (%) | 18.7% | 28.6% | 0.618 | 27.5% | 28.6% | 1.000 |
DCR (%) | 82.4% | 85.7% | 1.000 | 79.1% | 85.7% | 1.000 |
Platelet ≧ 7.5 × 104/μL (n = 98) | Platelet < 7.5 × 104/μL (n = 6) | p-value | Platelet ≧ 7.5 × 104/μL (n = 98) | Platelet < 7.5 × 104/μL (n = 6) | p-value | |
ORR (%) | 18.4% | 33.3% | 0.325 | 26.5% | 50.0% | 0.345 |
DCR (%) | 79.6% | 83.3% | 1.000 | 77.6% | 66.7% | 0.620 |
1st–2nd line (n = 85) | 3rd line (n = 19) | p-value | 1st–2nd line (n = 85) | 3rd line (n = 19) | p-value | |
ORR (%) | 21.2% | 10.5% | 0.355 | 31.8% | 10.5% | 0.089 |
DCR (%) | 78.8% | 84.2% | 0.758 | 74.1% | 89.5% | 0.230 |
Viral (n = 51) | Non-viral (n = 53) | p-value | Viral (n = 51) | Non-viral (n = 53) | p-value | |
ORR (%) | 17.7% | 20.8% | 0.805 | 23.5% | 32.1% | 0.386 |
DCR (%) | 80.4% | 79.3% | 1.000 | 72.6% | 81.1% | 0.356 |
BCLC-B (n = 41) | BCLC-C (n = 63) | p-value | BCLC-B (n = 41) | BCLC-C (n = 63) | p-value | |
ORR (%) | 19.5% | 19.0% | 1.000 | 34.2% | 23.8% | 0.271 |
DCR (%) | 87.5% | 76.4% | 0.290 | 87.5% | 72.2% | 0.130 |
mALBI 1-2a (n = 73) | mALBI 2b (n = 31) | p-value | mALBI 1-2a (n = 73) | mALBI 2b (n = 31) | p-value | |
ORR (%) | 21.9% | 12.9% | 0.416 | 31.5% | 19.4% | 0.240 |
DCR (%) | 78.1% | 83.9% | 0.600 | 76.7% | 77.4% | 1.000 |
<50% liver involvement (n = 90) | ≧50% liver involvement (n = 14) | p-value | <50% liver involvement (n = 90) | ≧50% liver involvement (n = 14) | p-value | |
ORR (%) | 20.0% | 14.3% | 1.000 | 26.0% | 14.3% | 0.340 |
DCR (%) | 80.0% | 78.6% | 1.000 | 76.7% | 78.6% | 1.000 |
Up-to-7 in (n = 27) | Up-to-7 out (n = 77) | p-value | Up-to-7 in (n = 27) | Up-to-7 out (n = 77) | p-value | |
ORR (%) | 40.7% | 11.7% | 0.003 | 48.2% | 20.8% | 0.002 |
DCR (%) | 88.9% | 76.6% | 0.265 | 85.2% | 74.0% | 0.296 |
Vp − (n = 88) | Vp + (n = 16) | p-value | Vp − (n = 88) | Vp + (n = 16) | p-value | |
ORR (%) | 21.6% | 6.3% | 0.298 | 31.8% | 6.3% | 0.037 |
DCR (%) | 83.0% | 62.5% | 0.087 | 79.6% | 62.5% | 0.194 |
Overall | |||
---|---|---|---|
Discontinuation due to AE n, (%) | 7 (6.1) | ||
Interruption of Atezo n, (%) | 17 (14.8) | ||
Interruption of Bev n, (%) | 30 (26.1) | ||
IMbrave150 in (n = 43) | IMbrave150 out (n = 72) | p-value | |
Discontinuation due to AE n, (%) | 1 (2.3) | 6 (8.3) | 0.254 |
Interruption of Atezo n, (%) | 1 (2.3) | 16 (22.2) | 0.003 |
Interruption of Bev n, (%) | 8 (18.6) | 22 (30.6) | 0.191 |
1st line (n = 55) | 2nd line (n = 60) | p-value | |
Discontinuation due to AE n, (%) | 4 (7.3) | 3 (5.0) | 0.710 |
Interruption of Atezo n, (%) | 5 (9.1) | 12 (20.0) | 0.120 |
Interruption of Bev n, (%) | 13 (23.6) | 17 (28.3) | 0.672 |
Child-Pugh A (n = 106) | Child-Pugh B (n = 9) | p-value | |
Discontinuation due to AE n, (%) | 6 (5.7) | 1 (11.1) | 0.444 |
Interruption of Atezo n, (%) | 13 (12.3) | 4 (44.4) | 0.026 |
Interruption of Bev n, (%) | 26 (24.5) | 4 (44.4) | 0.237 |
Proteinuria 0-1+ (n = 98) | Proteinuria 2+ (n = 8) | p-value | |
Discontinuation due to AE n, (%) | 6 (6.1) | 1 (12.5) | 0.423 |
Interruption of Atezo n, (%) | 14 (14.3) | 2 (25.0) | 0.347 |
Interruption of Bev n, (%) | 26 (26.5) | 3 (37.5) | 0.681 |
Platelet ≧ 7.5 × 104/μL (n =108) | Platelet < 7.5 × 104/μL (n = 7) | p-value | |
Discontinuation due to AE n, (%) | 7 (6.5) | 0 (0.0) | 1.000 |
Interruption of Atezo n, (%) | 14 (13.0) | 3 (42.9) | 0.065 |
Interruption of Bev n, (%) | 26 (24.1) | 4 (57.1) | 0.075 |
1st–2nd line (n = 85) | 3rd line (n = 19) | p-value | |
Discontinuation due to AE n, (%) | 7 (7.3) | 0 (0.0) | 0.598 |
Interruption of Atezo n, (%) | 13 (13.5) | 4 (21.1) | 0.478 |
Interruption of Bev n, (%) | 22 (22.9) | 8 (42.1) | 0.093 |
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Sho, T.; Suda, G.; Yamamoto, Y.; Furuya, K.; Baba, M.; Ogawa, K.; Kubo, A.; Tokuchi, Y.; Fu, Q.; Yang, Z.; et al. Efficacy and Effect on Liver Functional Reserve of Atezolizumab and Bevacizumab for Unresectable Hepatocellular Carcinoma in Patients Who Do Not Meet Eligibility Criteria of IMbrave150. Cancers 2022, 14, 3938. https://doi.org/10.3390/cancers14163938
Sho T, Suda G, Yamamoto Y, Furuya K, Baba M, Ogawa K, Kubo A, Tokuchi Y, Fu Q, Yang Z, et al. Efficacy and Effect on Liver Functional Reserve of Atezolizumab and Bevacizumab for Unresectable Hepatocellular Carcinoma in Patients Who Do Not Meet Eligibility Criteria of IMbrave150. Cancers. 2022; 14(16):3938. https://doi.org/10.3390/cancers14163938
Chicago/Turabian StyleSho, Takuya, Goki Suda, Yoshiya Yamamoto, Ken Furuya, Masaru Baba, Koji Ogawa, Akinori Kubo, Yoshimasa Tokuchi, Qingjie Fu, Zijian Yang, and et al. 2022. "Efficacy and Effect on Liver Functional Reserve of Atezolizumab and Bevacizumab for Unresectable Hepatocellular Carcinoma in Patients Who Do Not Meet Eligibility Criteria of IMbrave150" Cancers 14, no. 16: 3938. https://doi.org/10.3390/cancers14163938