Table 2.
The characteristics of the 8 published phase 1/2/3 studies of tivantinib in HCC.
| Study and references | Study area | Clinical phase | Cancer type, Number of patients | Age (years) | Therapies (Tivantinib) | Biomarker analysis (number of patients) | Therapeutic effects | Adverse events (%) |
|---|---|---|---|---|---|---|---|---|
| Santoro et al. (54) | Italy, Belgium, Germany, Canada, and USA | I | HCC, 21 | 47-80 | 360 mg, Orally, BID | NA | NA | 11 patients (52%), including neutropenia, anemia, leucopaenia, etc. |
| Santoro et al. (42) | Italy, Belgium, Germany, Canada, and USA | II/Randomized | Advanced HCC, 107 | 27-85 | 240 mg vs 360 mg vs Placebo, Orally, BID | MET overexpression (34.6%) | Time to progression was longer for patients treated with tivantinib (1.6 months) than placebo (1.4 months); HR= 0.64, 90% CI: 0.43–0.94, P=0.04. | Neutropenia (14%) |
| Rimassa et al. (55) | International Multi-center Clinical Trial | III/Randomized | Advanced,MET-high HCC, 303 | NA | 120 mg vs Placebo, Orally, BID | MET overexpression (100%) | NA | NA |
| Puzanov et al. (56) | USA and Italy | I | Advanced HCC, 20 | 41-77 | 240 mg + sorafenib 400 mg, Orally, BID | MET-High (40%) | The overall response rate was 10%, the disease control rate was 65%. The median PFS was 3.5 months (95% CI: 3.0-11.1 months). | Rash (40%), diarrhea (38%), and anorexia (33%) |
| Okusaka et al. (57) | Japan | I | Advanced HCC, 28 | Median: 65 | 120 mg vs 240 mg, Orally, BID | NA | NA | 120 mg was considered tolerable, while 240 mg were associated with neutropenia or febrile neutropenia |
| Rimassa et al. (41) | Multi-center Clinical Trial | II/Randomized | HCC, 77 | 27-85 | NA | MET-High (48%) | Survival in circulating MET-High patients was 7.0 months on tivantinib and 3.8 months on placebo, (HR 0.55, 95% CI, 0.28-1.06, P=0.07). The OS in circulating MET-Low patients was 7.5 months on tivantinib and 9.4 months on placebo, (HR 0.97, 95% CI, 0.51-1.85, P= 0.93) |
NA |
| Rimassa et al. (58) | Australia, the Americas, Europe, and New Zealand | III/Randomized | Unresectable, progressed, or intolerant to sorafenib, 340 | 19-87 | 120 mg vs Placebo, Orally, BID | MET-High (53%) | Median overall survival was 8.4 months (95% CI 6.8–10.0) in the tivantinib group and 9.1 months (7.3–10.4) in the placebo group (HR=0.97, 95% CI: 0.75–1.25, P=0.81). | Ascites (7%), anaemia (5%), abdominal pain (4%), and neutropenia (4%). |
| Kudo et al. (59) | Japan | III/Randomized | MET-high HCC, 195 | 36-86 | 120 mg vs Placebo, Orally, BID | MET-High (52.3%) | Median PFS was 2.8 and 2.3 months in the tivantinib and placebo groups, respectively (HR= 0.74, 95% CI: 0.52-1.04, P= 0.082). Median OS was 10.3 and 8.5 months in the tivantinib and placebo group, respectively (HR= 0.82, 95% CI: 0.58-1.15, P>0.05). | Neutropenia (31.6%), leukocytopenia (24.8%), and anemia (12.0%) |
NA, Not available; HCC, Hepatocellular carcinoma; HR, Hazard ratio; CI, Confidence interval; OS, Overall Survival; PFS, Progress Free Survival.