Table 2.
Selected Clinical Studies of Cabozantinib in Hepatocellular Carcinoma
| Trial with Survival Results | NCT0094022531 | CELESTIAL33 | |
|---|---|---|---|
| Phase | II Randomized Discontinuation | III | |
| Primary Endpoint | Lead-in stage: ORR Randomized stage: PFS | OS | |
| Treatment arms | Cabozantinib (N=41) | Cabozantinib (N=470) | Placebo (N=237) |
| mPFS (months) (95% CI) | 5.2 (N/A) | 5.2 (4.0–5.5) | 1.9 (1.9–1.9) |
| HR of mPFS (95% CI); P-value | N/A | 0.44 (0.36–0.52); <0.001 | |
| ORR (%) (95% CI) | 5 (N/A) | 4 (N/A) | <1 (N/A) |
| mOS (months) (95% CI) | 11.5 (7.3–15.6) | 10.2 (9.1–12.0) | 8.0 (6.8–9.4) |
| HR of mOS (95% CI); P-value | N/A | 0.76 (0.63–0.92); 0.005 | |
| ECOG 0 (%) | 44 | 52 | 55 |
| ECOG 1 (%) | 56 | 48 | 45 |
| ECOG 2 (%) | 0 | <1 | 0 |
| Any grade adverse events (%) | 100 | 99 | 92 |
| Most common all-grade adverse events (%) | Diarrhea (63), Hand-foot syndrome (56), Fatigue (56) | Diarrhea (54), Decreased appetite (48), Palmar-Plantar Erythrodysesthesia (46) | Fatigue (30), Abdominal pain (25), Diarrhea (19), Constipation (19) |
| Most common ≥ grade 3 adverse events (%) | Diarrhea (20), Hand-foot syndrome (15), Thrombocytopenia (15) | Palmar-Plantar Erythrodysesthesia (17), Hypertension (16), Diarrhea (10), Fatigue (10) | Increase AST (6), Ascites (5), Anemia (5) |
Abbreviations: PFS, progression-free survival; OS, overall survival; ORR, overall response rate; HR, hazard ratio; CI, confidence interval.