Early Tumor Response and Safety of Atezolizumab Plus Bevacizumab for Patients with Unresectable Hepatocellular Carcinoma in Real-World Practice
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Treatment Regimens
2.3. Assessment of Response to Therapy
2.4. Safety Assessment
2.5. Statistical Analysis
3. Results
3.1. Patient Background Characteristics
3.2. Tumor Responses
3.3. Changes in Tumor Markers
3.4. Correlation between Assessment by Tumor Markers and mRECIST
3.5. Adverse Events
3.6. Change in ALBI Score
3.7. Change in Serum Ammonia Level
4. Discussion
5. Conclusion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Characteristic | All Patients (n = 40) | 1st Line Patients (n = 16) | 2nd Line or Later Patients (n = 24) | p-Value * |
---|---|---|---|---|
Age (yr), range | 69 (47–90) | 69 (55–90) | 70 (47–87) | 0.383 |
Sex (males/females), n | 30/10 | 11/5 | 19/5 | 0.482 |
Etiology (Viral/NBNC), n | 26/14 | 11/5 | 15/9 | 0.746 |
Child-Pugh score (5/6), n | 21/19 | 11/5 | 10/14 | 0.117 |
Modified ALBI grade (1–2a/2b), n | 23/17 | 12/4 | 11/13 | 0.104 |
ALBI score | −2.40 (–3.07–1.47) | –2.65 (–3.07–1.47) | –2.24 (–2.94–1.83) | 0.048 |
Serum ammonia level (μg/dL), range | 29 (10–149) | 29 (13–79) | 29 (10–149) | 0.793 |
Size of main tumor (intrahepatic) (mm), range | 40 (0–130) | 40 (0–130) | 38 (0–130) | 0.934 |
Relative tumor size (<50%/≥50%), n | 36/4 | 16/0 | 20/4 | 0.278 |
MVI (absent/present), n | 28/12 | 11/5 | 17/7 | 1.0 |
EHM (absent/present), n | 24/16 | 13/3 | 11/13 | 0.047 |
BCLC stage (B/C), n | 18/22 | 9/7 | 9/15 | 0.335 |
Serum AFP level (ng /mL), range | 79.0 (1.8–35,780) | 174.1 (2.3–35,780) | 79.0 (1.8–34,200) | 0.730 |
Serum DCP level (mAU/mL), range | 347 (15–108,710) | 292 (19–35,040) | 446 (15–108,710) | 0.945 |
Observation period (day), range | 120 (42–174) | 100 (42–184) | 136 (46–188) | 0.204 |
Line | Treatment | n |
---|---|---|
2nd line | Len | 14 |
Sor | 1 | |
Investigational products | 1 | |
3rd line | Len→Sor | 1 |
Len→Ram | 1 | |
4th line | Len→Sor→Reg | 2 |
Sor→Reg→Len | 2 | |
5th line | Len→Sor→Reg→Ram | 1 |
Sor→Reg→Len→Ram | 1 |
mRECIST | RECIST 1.1 | ||||||||
---|---|---|---|---|---|---|---|---|---|
% (n) | All Patients | 1st Line Patients | 2nd Line or Later Patients | Difference | % (n) | All Patients | 1st Line Patients | 2nd Line or LaterPatients | Difference |
(n = 40) | (n = 16) | (n = 24) | (p-Value *) | (n = 40) | (n = 16) | (n = 24) | (p-Value *) | ||
Confirmed ORR | 22.5 (9) | 37.5 (6) | 12.5 (3) | 0.12 | Confirmed ORR | 7.5 (3) | 6.2 (1) | 8.3 (2) | 1 |
CR | 0 (0) | 0 (0) | 0 (0) | CR | 0 (0) | 0 (0) | 0 (0) | ||
PR | 22.5 (9) | 37.5 (6) | 12.5 (3) | PR | 7.5 (3) | 6.2 (1) | 8.3 (2) | ||
SD | 50.0 (20) | 43.8 (7) | 54.2 (13) | SD | 67.5 (27) | 81.3 (13) | 58.4 (14) | ||
PD | 25.0 (10) | 12.5 (2) | 33.3 (8) | PD | 25.0 (10) | 12.5 (2) | 33.3 (8) | ||
N.E | 2.5 (1) | 6.2 (1) | 0 (0) | N.E | 0 (0) | 0 (0) | 0 (0) | ||
DCR | 72.5 (29) | 81.3 (13) | 66.7 (16) | 0.477 | DCR | 75.0 (30) | 87.5 (14) | 66.7 (16) | 0.473 |
Variable | Univariate | Multivariate | ||
---|---|---|---|---|
p-Value * | OR | 95% CI | p-Value ** | |
Age (yr) (<70 vs. ≥70) | 1.0 | |||
Sex (male vs. female) | 1.0 | |||
Etiology (Viral vs. NBNC) | 0.694 | |||
ECOG performance status (0 vs. 1) | 1.0 | |||
Child-Pugh score (5 vs. 6) | 0.021 | |||
Modified ALBI grade (1 or 2a vs. 2b) | 0.256 | |||
Relative tumor volume (<50% vs. ≥50%) | 0.570 | |||
MVI (absent vs present) | 0.697 | |||
EHM (absent vs present) | 0.272 | |||
Serum AFP level (<400 vs. ≥400) | 0.690 | |||
Serum DCP level (<340 vs. ≥340) | 0.060 | |||
History of systemic therapy (without vs. with) | 0.120 | |||
AFP ratio at 3weeks (<1.0 vs. ≥1.0) | 0.014 | 21.3 | 2.01–225.0 | 0.011 |
DCP ratio at 3weeks (<1.0 vs. ≥1.0) | 0.705 |
Event% (n) | All Patients (n = 40) | 1st Line Patients (n = 16) | 2nd Line or Later Patients (n = 24) | Difference (p-Value *) | ||||
---|---|---|---|---|---|---|---|---|
Any Grade | Grade 3 or 4 | Time (Days) | Any Grade | Grade 3 or 4 | Any Grade | Grade 3 or 4 | ||
Hypertension | 60.0 (24) | 10.0 (4) | 24 (2–73) | 68.8 (11) | 12.5 (2) | 54.2 (13) | 8.3 (2) | 0.512 |
Fatigue | 57.5 (23) | 2.5 (1) | 22 (6–155) | 68.8 (11) | 0 | 50.0 (12) | 4.2 (1) | 0.332 |
Decreased appetite | 57.5 (23) | 2.5 (1) | 21 (3–155) | 56.3 (9) | 1 (6.3) | 58.3 (14) | 0 | 1.0 |
Pruritus | 50.0 (20) | 0 | 21 (6–85) | 56.3 (9) | 0 | 45.8 (11) | 0 | 0.748 |
Proteinuria | 37.5 (15) | 7.5 (3) | 23 (6–101) | 25.0 (4) | 6.3 (1) | 45.8 (11) | 8.3 (2) | 0.74 |
Pyrexia | 35.0 (14) | 2.5 (1) | 11 (4–77) | 43.8 (7) | 0 | 29.2 (7) | 4.2 (1) | 0.5 |
Edema | 25.0 (10) | 2.5 (1) | 24 (16–133) | 18.8 (3) | 0 | 29.2 (7) | 4.2 (1) | 0.711 |
Increased AST or ALT | 20.0 (8) | 7.5 (3) | 16 (2–41) | 25.0 (4) | 6.3 (1) | 16.7 (4) | 8.3 (2) | 0.69 |
Ascites | 15.0 (6) | 0 | 15 (6–69) | 6.3 (1) | 0 | 20.8 (5) | 0 | 0.373 |
Rash | 15.0 (6) | 0 | 29 (7–71) | 12.5 (2) | 0 | 16.7 (4) | 0 | 1.0 |
Diarrhea | 12.5 (5) | 0 | 21 (15–171) | 12.5 (2) | 0 | 12.5 (3) | 0 | 1.0 |
Thyroid dysfunction | 10.0 (4) | 0 | 44 (37–174) | 12.5 (2) | 0 | 8.3 (2) | 0 | 1.0 |
Gastrointestinal bleeding | 7.5 (3) | 7.5 (3) | 6.3 (1) | 6.3 (1) | 8.3 (2) | 8.3 (2) | 1.0 | |
Portal vein thrombus | 2.5 (1) | 0 | 0 | 0 | 4.2 (1) | 0 | 1.0 | |
Stroke | 2.5 (1) | 0 | 0 | 0 | 4.2 (1) | 0 | 1.0 |
Atezo + Bev | |||||
Hypertension | (+) | (−) | Incidence rate (%) | p-value * | |
Prior MTA | (+) | 11 | 9 | 55.0 | 1.0 |
(−) | 2 | 2 | 50.0 | ||
Atezo + Bev | |||||
Fatigue | (+) | (−) | Incidence rate (%) | p-value * | |
Prior MTA | (+) | 10 | 3 | 76.9 | 0.012 |
(−) | 2 | 9 | 18.2 | ||
Atezo + Bev | |||||
Decreased appetite | (+) | (−) | Incidence rate (%) | p-value * | |
Prior MTA | (+) | 10 | 5 | 66.7 | 0.403 |
(−) | 4 | 5 | 44.4 | ||
Atezo + Bev | |||||
Pruritus | (+) | (−) | Incidence rate (%) | p-value * | |
Prior MTA | (+) | 2 | 2 | 50.0 | 1.0 |
(−) | 9 | 11 | 45.0 | ||
Atezo + Bev | |||||
Proteinuria | (+) | (−) | Incidence rate (%) | p-value * | |
Prior MTA | (+) | 9 | 3 | 75.0 | 0.012 |
(−) | 2 | 10 | 16.7 | ||
Atezo + Bev | |||||
Pyrexia | (+) | (−) | Incidence rate (%) | p-value * | |
Prior MTA | (+) | 2 | 0 | 100 | 0.076 |
(−) | 5 | 17 | 22.7 | ||
Atezo + Bev | |||||
Edema | (+) | (−) | Incidence rate (%) | p-value * | |
Prior MTA | (+) | 2 | 6 | 25.0 | 1.0 |
(−) | 5 | 11 | 31.2 | ||
Atezo + Bev | |||||
Increased AST/ALT | (+) | (−) | Incidence rate (%) | p-value * | |
Prior MTA | (+) | 1 | 4 | 20.0 | 1.0 |
(−) | 3 | 16 | 15.8 | ||
Atezo + Bev | |||||
Ascites | (+) | (−) | Incidence rate (%) | p-value * | |
Prior MTA | (+) | 4 | 3 | 57.1 | 0.015 |
(−) | 1 | 16 | 5.9 | ||
Atezo + Bev | |||||
Rash | (+) | (−) | Incidence rate (%) | p-value * | |
Prior MTA | (+) | 0 | 4 | 0 | 1.0 |
(−) | 4 | 16 | 20.0 | ||
Atezo + Bev | |||||
Diarrhea | (+) | (−) | Incidence rate (%) | p-value * | |
Prior MTA | (+) | 0 | 8 | 0 | 0.526 |
(−) | 3 | 13 | 18.8 | ||
Atezo + Bev | |||||
Thyroid dysfunction | (+) | (−) | Incidence rate (%) | p-value * | |
Prior MTA | (+) | 2 | 10 | 16.7 | 0.478 |
(−) | 0 | 12 | 0 |
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Ando, Y.; Kawaoka, T.; Kosaka, M.; Shirane, Y.; Johira, Y.; Miura, R.; Murakami, S.; Yano, S.; Amioka, K.; Naruto, K.; et al. Early Tumor Response and Safety of Atezolizumab Plus Bevacizumab for Patients with Unresectable Hepatocellular Carcinoma in Real-World Practice. Cancers 2021, 13, 3958. https://doi.org/10.3390/cancers13163958
Ando Y, Kawaoka T, Kosaka M, Shirane Y, Johira Y, Miura R, Murakami S, Yano S, Amioka K, Naruto K, et al. Early Tumor Response and Safety of Atezolizumab Plus Bevacizumab for Patients with Unresectable Hepatocellular Carcinoma in Real-World Practice. Cancers. 2021; 13(16):3958. https://doi.org/10.3390/cancers13163958
Chicago/Turabian StyleAndo, Yuwa, Tomokazu Kawaoka, Masanari Kosaka, Yuki Shirane, Yusuke Johira, Ryoichi Miura, Serami Murakami, Shigeki Yano, Kei Amioka, Kensuke Naruto, and et al. 2021. "Early Tumor Response and Safety of Atezolizumab Plus Bevacizumab for Patients with Unresectable Hepatocellular Carcinoma in Real-World Practice" Cancers 13, no. 16: 3958. https://doi.org/10.3390/cancers13163958