Early Changes in Alpha-Fetoprotein and Des-γ-Carboxy Prothrombin Are Useful Predictors of Antitumor Response to Durvalumab Plus Tremelimumab Therapy for Advanced Hepatocellular Carcinoma
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Dur/Tre Treatment, Evaluation of Adverse Events, and Changes in Liver Function
2.3. Determination of Antitumor Response
2.4. Evaluation of Changes in AFP, DCP, and AFP-L3
2.5. Statistical Analysis
3. Results
3.1. Patient Characteristics at Baseline
3.2. Antitumor Response at 8 Weeks after Dur/Tre Initiation According to RECIST 1.1 and mRECIST
3.3. PFS and OS by 8W-RECIST 1.1
3.4. AFP Ratios at 2, 4, and 8 Weeks after Dur/Tre Initiation, Stratified by 8W-RECIST 1.1
3.5. DCP Ratios at 2, 4, and 8 Weeks after Dur/Tre Initiation, Stratified by 8W-RECIST 1.1
3.6. AFP-L3 Ratios at 4 and 8 Weeks after Dur/Tre Initiation, Stratified by 8W-RECIST 1.1
3.7. Prognostic Factors at Start of Dur/Tre Associated with Good PFS
3.8. PFS by Treatment Line and NLR
3.9. Safety and Changes in Liver Function
3.10. Post-Progression Therapy
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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Patient Characteristics | n = 40 |
---|---|
Age, years; median (range) | 75 (40–91) |
Sex, male/female | 33/7 |
Etiology, HBV/HCV/non-viral | 6/9/25 |
Treatment line, 1st/2nd/3rd/4th/5th | 18/7/11/2/2 |
ECOG-PS, 0/1 | 33/7 |
Child–Pugh score, 5/6/7/8/9 | 20/13/5/1/1 |
mALBI grade, 1/2a/2b/3 | 12/9/19/1 |
BCLC stage, A/B/C | 1/22/17 |
Intrahepatic tumor number, <4/≥4 | 11/29 |
Maximum intrahepatic tumor size, <50 mm/≥50 mm | 26/14 |
Portal vein tumor thrombosis, 0/1/2/3/4 | 30/0/5/4/1 |
Extrahepatic metastasis, −/+ | 27/13 |
AFP level, ng/mL; median (range) | 108 (1.3–31,676) |
DCP level, mAU/mL; median (range) | 603 (10–162,000) |
AFP-L3 level, %; median (range) | 16.6 (<0.5–88.8) |
NLR; median (range) | 2.66 (1.03–10.95) |
Observation period, months; median (range) | 7.6 (1.5–16.0) |
CR n (%) | PR n (%) | SD n (%) | PD n (%) | NE n (%) | CRR | ORR | DCR | |
---|---|---|---|---|---|---|---|---|
8W-RECIST 1.1 | 0 (0) | 10 (25.0) | 13 (32.5) | 16 (40.0) | 1 (2.5) | 0% | 25.0% | 57.5% |
8W-mRECIST | 3 (7.5) | 9 (22.5) | 11 (27.5) | 16 (40.0) | 1 (2.5) | 7.5% | 30.0% | 57.5% |
8W-RECIST 1.1 | AFP Ratios, Median (SE) | p Value | |||||
---|---|---|---|---|---|---|---|
CR+PR (8W-OR) n = 8 | SD n = 7 | PD+NE (Non-8W-DC) n = 12 | CR+PR+SD (8W-DC) n = 15 | SD+PD+NE (Non-8W-OR) n = 19 | 8W-OR vs. Non-8W-OR | 8W-DC vs. Non-8W-DC | |
At 2W | 0.83 (0.26) | 0.85 (0.06) | 1.16 (0.13) | 0.84 (0.13) | 1.07 (0.10) | 0.3033 | 0.0127 |
At 4W | 0.39 (0.19) | 1.00 (0.13) | 1.22 (0.32) | 0.53 (0.12) | 1.08 (0.23) | 0.0068 | 0.0006 |
At 8W | 0.21 (0.25) | 0.89 (0.21) | 1.91 (0.92) | 0.88 (0.18) | 1.53 (0.61) | 0.0029 | 0.0015 |
8W-RECIST 1.1 | DCP Ratios, Median (SE) | p Value | |||||
---|---|---|---|---|---|---|---|
CR+PR (8W-OR) n = 10 | SD n = 11 | PD+NE (Non-8W-DC) n = 16 | CR+PR+SD (8W-DC) n = 21 | SD+PD+NE (Non-8W-OR) n = 27 | 8W-OR vs. Non-8W-OR | 8W-DC vs. Non-8W-DC | |
At 2W | 0.46 (0.23) | 1.21 (1.45) | 1.13 (0.34) | 0.86 (0.83) | 1.15 (0.61) | 0.0049 | 0.2057 |
At 4W | 0.15 (0.04) | 1.52 (0.43) | 1.23 (0.93) | 0.49 (0.29) | 1.46 (0.58) | <0.0001 | 0.0215 |
At 8W | 0.06 (0.06) | 1.26 (0.31) | 1.83 (1.51) | 0.50 (0.24) | 1.70 (0.94) | <0.0001 | 0.0032 |
8W-RECIST 1.1 | AFP-L3 Ratios, Median (SE) | p Value | |||||
---|---|---|---|---|---|---|---|
CR+PR (8W-OR) n = 9 | SD n = 11 | PD+NE (Non-8W-DC) n = 13 | CR+PR+SD (8W-DC) n = 20 | SD+PD+NE (Non-8W-OR) n = 24 | 8W-OR vs. Non-8W-OR | 8W-DC vs. Non-8W-DC | |
At 4W | 0.93 (0.15) | 1.01 (0.06) | 1.01 (0.08) | 1.00 (0.08) | 1.01 (0.05) | 0.3675 | 0.9388 |
At 8W | 1.00 (0.48) | 1.07 (0.09) | 1.06 (0.09) | 1.03 (0.21) | 1.06 (0.06) | 0.4188 | 0.6060 |
Factors | Univariate Analysis | Multivariate Analysis | ||
---|---|---|---|---|
HR (95%CI) | p Value | HR (95%CI) | p Value | |
Age (<75 years) | 0.841 (0.381–1.857) | 0.6685 | ||
Sex (female) | 1.588 (0.591–4.271) | 0.3594 | ||
Etiology (HBV or HCV) | 1.390 (0.619–3.117) | 0.4248 | ||
Treatment line (1st) | 0.404 (0.171–0.958) | 0.0395 | 0.374 (0.156–0.896) | 0.0274 |
ECOG-PS (0) | 0.536 (0.199–1.441) | 0.2164 | ||
Child–Pugh score (5) | 0.728 (0.330–1.606) | 0.4320 | ||
BCLC stage (A or B) | 0.642 (0.292–1.411) | 0.2697 | ||
Number of intrahepatic tumors (≥4) | 1.216 (0.452–3.269) | 0.6986 | ||
Maximum size of intrahepatic tumors (≥50 mm) | 0.851 (0.365–1.983) | 0.7088 | ||
Portal vein tumor thrombosis (+) | 1.466 (0.624–3.444) | 0.3804 | ||
Extrahepatic metastasis (+) | 0.528 (0.236–1.181) | 0.1200 | ||
AFP level (≥100 ng/mL) | 1.470 (0.660–3.277) | 0.3458 | ||
DCP level (≥400 mAU/mL) | 1.105 (0.502–2.432) | 0.8039 | ||
AFP-L3 level (≥10.0%) | 1.044 (0.458–2.380) | 0.9178 | ||
NLR (≤3.00) | 0.477 (0.211–2.347) | 0.0757 | 0.433 (0.188–0.996) | 0.0490 |
Adverse Event | Any Grade n (%) | Grade 1/2 n (%) | Grade 3/4 n (%) |
---|---|---|---|
Fever | 8 (20.0) | 8 (20.0) | 0 |
Diarrhea | 7 (17.5) | 2 (5.0) | 5 (12.5) |
Anorexia | 7 (17.5) | 6 (15.0) | 1 (2.5) |
General fatigue | 7 (17.5) | 7 (17.5) | 0 |
Pruritus | 7 (17.5) | 7 (17.5) | 0 |
Elevated aspartate aminotransferase | 3 (7.5) | 1 (2.5) | 2 (5.0) |
Skin rash | 3 (7.5) | 3 (7.5) | 0 |
Deterioration of liver function | 2 (5.0) | 0 | 2 (5.0) |
Reduced adrenal function | 1 (2.5) | 1 (2.5) | 0 |
Hypothyroidism | 1 (2.5) | 1 (2.5) | 0 |
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Share and Cite
Kuzuya, T.; Kawabe, N.; Muto, H.; Wada, Y.; Komura, G.; Nakano, T.; Tanaka, H.; Nakaoka, K.; Ohno, E.; Funasaka, K.; et al. Early Changes in Alpha-Fetoprotein and Des-γ-Carboxy Prothrombin Are Useful Predictors of Antitumor Response to Durvalumab Plus Tremelimumab Therapy for Advanced Hepatocellular Carcinoma. Curr. Oncol. 2024, 31, 4225-4240. https://doi.org/10.3390/curroncol31080315
Kuzuya T, Kawabe N, Muto H, Wada Y, Komura G, Nakano T, Tanaka H, Nakaoka K, Ohno E, Funasaka K, et al. Early Changes in Alpha-Fetoprotein and Des-γ-Carboxy Prothrombin Are Useful Predictors of Antitumor Response to Durvalumab Plus Tremelimumab Therapy for Advanced Hepatocellular Carcinoma. Current Oncology. 2024; 31(8):4225-4240. https://doi.org/10.3390/curroncol31080315
Chicago/Turabian StyleKuzuya, Teiji, Naoto Kawabe, Hisanori Muto, Yuryo Wada, Gakushi Komura, Takuji Nakano, Hiroyuki Tanaka, Kazunori Nakaoka, Eizaburo Ohno, Kohei Funasaka, and et al. 2024. "Early Changes in Alpha-Fetoprotein and Des-γ-Carboxy Prothrombin Are Useful Predictors of Antitumor Response to Durvalumab Plus Tremelimumab Therapy for Advanced Hepatocellular Carcinoma" Current Oncology 31, no. 8: 4225-4240. https://doi.org/10.3390/curroncol31080315