Background
Phase II-III, open-label, randomized, N=294 (148 perioperative, 146 surgery alone), 16 hospitals in China. Resectable HCC at intermediate-to-high recurrence risk (CNLC stage Ib-IIIa), 87% male, 99% Han Chinese ethnicity. Tested perioperative camrelizumab + rivoceranib to reduce high post-resection recurrence.
Interventions and follow up
Arm A: Neoadjuvant camrelizumab 200 mg Q2W + rivoceranib 250 mg daily x 2 cycles, then surgery, then adjuvant camrelizumab 200 mg Q3W + rivoceranib (≥6 cycles)
Arm B: Upfront surgery alone
Primary endpoint: Event-free survival (EFS)
Median follow up: 21.3 months at prespecified interim analysis
Arm B: Upfront surgery alone
Primary endpoint: Event-free survival (EFS)
Median follow up: 21.3 months at prespecified interim analysis
Results
Event-free survival: Median 42.1 vs 19.4 months, HR 0.59, 95% CI 0.41-0.85, P=.0040
Major pathologic response: 35.1% (perioperative; 3.4% pathologic complete response) vs 7.5%
Overall survival at 24 months: 79% vs 61%, HR 0.59, 95% CI 0.41-0.85, P=.005
Major pathologic response: 35.1% (perioperative; 3.4% pathologic complete response) vs 7.5%
Overall survival at 24 months: 79% vs 61%, HR 0.59, 95% CI 0.41-0.85, P=.005
Adverse events
Overall: Grade ≥3 treatment-related AE 37.6% (perioperative) vs 0% (surgery alone); 2 treatment-related deaths during neoadjuvant phase (hepatic failure; combined hepatic-renal failure)
Most common any-grade neoadjuvant TRAEs: hypertension 23.3%, stomatitis 11.6%, rash 9.3%
Most common any-grade neoadjuvant TRAEs: hypertension 23.3%, stomatitis 11.6%, rash 9.3%
Conclusions
Perioperative camrelizumab plus rivoceranib significantly improved EFS and OS in resectable HCC at intermediate-to-high recurrence risk, with neoadjuvant-plus-adjuvant immunotherapy-VEGF combination addressing the high recurrence rate in at-risk surgical candidates.
Key Limitations
Interim analysis at 21.3 months; open-label design; enrollment essentially limited to a Chinese population (87% Han, predominantly HBV-related HCC) limiting generalizability; 2 treatment-related deaths and notable hepatic toxicity warrant cautious patient selection.
Clinical Context
CARES-009 supports perioperative immunotherapy-VEGF combination as a benefit-risk-favorable strategy in high-risk resectable HCC, paralleling perioperative advances in other solid tumors. Positioning relative to current ESMO guidance and approved adjuvant atezolizumab-bevacizumab (IMbrave050) will depend on mature OS and broader-population data.
References