Response to Lenvatinib Is Associated with Optimal RelativeDose Intensity in Hepatocellular Carcinoma: Experience in Clinical Settings
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patient Characteristics
2.2. Treatment Protocol and Relative Dose Intensity
2.3. Evaluation Criteria for Adverse Events and Response
2.4. Ethical Considerations
2.5. Statistical Analysis
3. Results
3.1. Patient Characteristics
3.2. Adverse Events
3.3. Response
3.4. Overall Survival
3.5. Relative Dose Intensity and Radiological Response
3.6. Predictive Ability of Relative Dose Intensity for Radiological Response
3.7. Overall Survival Stratified by Relative Dose Intensity
4. Discussion
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Variable | n = 81 | |
---|---|---|
Age | year | 72.0 (41–88) |
Gender | male/female | 66/15 |
BMI | kg/m2 | 24.10 (17.5–34.4) |
Performance status | 0/1/2 | 48/28/5 |
Child–Pugh grade | A/B | 67/14 |
ALBI grade | 1/2/3 | 20/57/4 |
Macroscopic PV invasion | Vp3 or Vp4 | 14 (17.2) |
Extrahepatic spread | + | 34 (41.9) |
BCLC stage | A/B/C | 1/19/61 |
Etiology | HBV/HCV/NBNC | 22/26/33 |
Platelet count | ×104/μL | 12.30 (4.0–38.1) |
PT | % | 88.0 (47–128) |
T.bil | mg/dL | 0.90 (0.4–2.6) |
Albumin | g/dL | 3.50 (2.2–4.6) |
ALT | IU/mL | 27.0 (11–198) |
AFP | ng/ml | 68.8 (1.8–23,124) |
DCP | mAU/ml | 484.0 (10–990,474) |
Systemic therapy | naïve/experienced | 66/15 |
Dose reduction | at administration | 32 (39.5) |
Treatment-Emergent Adverse Events | Any Grade | Grade ≥ 3 |
---|---|---|
All adverse events | 79 (97.5%) | 35 (43.2%) |
Hypertension | 50 (61.7%) | 11 (13.6%) |
Fatigue | 47 (58.0%) | 1 (1.2%) |
Decreased appetite | 46 (56.7%) | 3 (3.7%) |
Hypothyroidism | 42 (51.8%) | 0 (0.0%) |
Proteinuria | 37 (45.6%) | 7 (8.6%) |
Palmar–plantar erythrodysesthesia syndrome | 31 (38.2%) | 0 (0.0%) |
Thrombocytopenia | 30 (37.0%) | 3 (3.7%) |
Elevated liver enzymes | 25 (30.8%) | 6 (7.4%) |
Diarrhea | 20 (24.6%) | 0 (0.0%) |
Weight loss | 18 (22.2%) | 1 (1.2%) |
Dysphonia | 12 (14.8%) | 0 (0.0%) |
edema | 11 (13.5%) | 1 (1.2%) |
Rash | 5 (6.1%) | 0 (0.0%) |
Loss of hair | 1 (1.2%) | 0 (0.0%) |
Response Category | Lenvatinib (n = 81) | |
---|---|---|
mRECIST | RECIST | |
Complete response (CR) | 7 (8.6%) | 3(3.7%) |
Partial response (PR) | 21 (25.9%) | 11 (13.6%) |
Stable disease (SD) | 23 (28.4%) | 38 (46.9%) |
Progressive disease (PD) | 20 (24.7%) | 23 (28.4%) |
Unknown or not evaluable | 10 (12.3%) | 6 (7.4%) |
Objective response (OR) | 28 (34.6%) | 14 (17.3%) |
Disease control (DC) | 51 (63.0%) | 52 (64.2%) |
Factors | Child–Pugh Grade | Performance Status | ||
---|---|---|---|---|
grade A (n = 67) | grade B (n = 14) | PS 0 (n =48) | PS 1/2 (n = 33) | |
Complete response (CR) | 3 (4.4%) | 0 (0.0%) | 2 (4.2%) | 1 (3.0%) |
Partial response (PR) | 11 (16.4%) | 0 (0.0%) | 10 (20.8%) | 1 (3.0%) |
Stable disease (SD) | 32 (47.7%) | 6 (42.9%) | 24 (50.0%) | 14 (42.4%) |
Progressive disease (PD) | 18 (26.8%) | 5 (35.7%) | 10 (20.8%) | 13 (39.3%) |
Unknown or not evaluable | 3 (4.4%) | 3 (21.4%) | 1 (2.1%) | 5 (15.1%) |
Objective response (OR) | 14 (20.8%) | 0 (0.0%) | 12 (25.0%) | 2 (6.0%) |
Disease control (DC) | 46 (68.6%) | 6 (42.9%) | 36 (75.0%) | 16 (48.4%) |
Variable | 8w-RDI ≥ 67.0% | 8w-RDI < 67.0% | p-Value | |
---|---|---|---|---|
Age | year | 71.0 (46–84) | 76.0 (41–88) | 0.065 |
Gender | male/female | 37/5 | 29/10 | 0.111 |
BMI | kg/m2 | 24.65 (18.6–33.6) | 22.15 (17.5–34.4) | 0.019 |
Performance status | 0/1/2 | 34/8/0 | 14/20/5 | <0.001 |
Child–Pugh grade | A/B | 38/4 | 29/10 | 0.055 |
ALBI grade | 1/2/3 | 11/31/0 | 9/26/4 | 0.103 |
Macroscopic PV invasion | Vp3 or Vp4 | 7 (16.7) | 7 (17.9) | 0.878 |
Extrahepatic spread | + | 16 (38.1) | 18 (46.2) | 0.462 |
BCLC stage | A/B/C | 1/16/25 | 0/3/36 | 0.002 |
Etiology | HBV/HCV/NBNC | 13/12/17 | 9/14/16 | 0.669 |
Platelet count | ×104/μL | 14.85 (4.6–38.1) | 10.60 (4.0–28.0) | 0.015 |
PT | % | 90.5 (64–128) | 84.0 (47–118) | 0.013 |
T.bil | mg/dL | 0.90 (0.4–1.8) | 1.00 (0.4–2.6) | 0.307 |
Albumin | g/dL | 3.70 (2.8–4.6) | 3.50 (2.2–4.5) | 0.028 |
ALT | IU/mL | 27.5 (11–143) | 26.0 (11–198) | 0.909 |
AFP | ng/mL | 43.0 (1.8–9926) | 140.0 (1.9–23,124) | 0.061 |
DCP | mAU/mL | 572.5 (10–78884) | 458.0 (11–990,474) | 0.609 |
Systemic therapy | naïve/experienced | 36/6 | 30/9 | 0.308 |
Dose reduction | at administration | 9 (21.4) | 23 (59.0) | <0.001 |
Results given as median (range) or n (%). |
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Sasaki, R.; Fukushima, M.; Haraguchi, M.; Miuma, S.; Miyaaki, H.; Hidaka, M.; Eguchi, S.; Matsuo, S.; Tajima, K.; Matsuzaki, T.; et al. Response to Lenvatinib Is Associated with Optimal RelativeDose Intensity in Hepatocellular Carcinoma: Experience in Clinical Settings. Cancers 2019, 11, 1769. https://doi.org/10.3390/cancers11111769
Sasaki R, Fukushima M, Haraguchi M, Miuma S, Miyaaki H, Hidaka M, Eguchi S, Matsuo S, Tajima K, Matsuzaki T, et al. Response to Lenvatinib Is Associated with Optimal RelativeDose Intensity in Hepatocellular Carcinoma: Experience in Clinical Settings. Cancers. 2019; 11(11):1769. https://doi.org/10.3390/cancers11111769
Chicago/Turabian StyleSasaki, Ryu, Masanori Fukushima, Masafumi Haraguchi, Satoshi Miuma, Hisamitsu Miyaaki, Masaaki Hidaka, Susumu Eguchi, Satoshi Matsuo, Kazuaki Tajima, Toshihisa Matsuzaki, and et al. 2019. "Response to Lenvatinib Is Associated with Optimal RelativeDose Intensity in Hepatocellular Carcinoma: Experience in Clinical Settings" Cancers 11, no. 11: 1769. https://doi.org/10.3390/cancers11111769