Hengrui's Perioperative Immunotherapy Combo Achieves Breakthrough in Hepatocellular Carcinoma Treatment
核心洞察
Hengrui (搜索)'s CARES-009 trial demonstrated that perioperative camrelizumab plus rivoceranib more than doubled event-free survival compared to surgery alone in resectable hepatocellular carcinoma (搜索) patients.
The combination achieved a major pathological response rate of 35.1% versus 7.5% with surgery alone, with manageable safety profile and only 8% discontinuation rate.
These results represent a potential paradigm shift in HCC (搜索) treatment, as no standard perioperative therapies currently exist for this cancer with high recurrence rates.
Jiangsu Hengrui Medicine has achieved a significant breakthrough in hepatocellular carcinoma (搜索) (HCC (搜索)) treatment, with their Phase III CARES-009 trial demonstrating that perioperative immunotherapy combination therapy more than doubles event-free survival in patients with resectable HCC. The results, presented at the European Society for Medical Oncology (ESMO) 2025 in Berlin, could reshape treatment paradigms for a cancer that affects over 188,000 patients annually in urban China alone.
Trial Design and Patient Population
The CARES-009 trial (NCT04521153) evaluated the combination of camrelizumab (AiRuiKa (搜索)), a PD-1 (搜索) inhibitor, and rivoceranib (AiTan), a VEGFR-2 (搜索) tyrosine kinase inhibitor, as perioperative treatment in Chinese patients with resectable HCC (搜索) at intermediate-to-high risk of recurrence. The study aimed to address a critical unmet medical need, as more than half of HCC patients relapse within two years after resection according to AASLD practice guidelines, and no current standard adjuvant or perioperative systemic therapies exist for this indication.
Efficacy Results Exceed Expectations
At a median follow-up of 21.3 months, the combination significantly improved event-free survival (EFS), meeting its primary endpoint versus surgery alone. The perioperative therapy achieved an EFS of 42.1 months (HR 0.63; 95% CI 0.44-0.90) compared to 19.4 months with surgery alone (HR 0.59; 95% CI 0.41-0.85; p = 0.0040), representing more than a doubling of the event-free period.
The major pathological response (MPR) rate was markedly higher with perioperative therapy at 35.1% versus 7.5% with surgery alone (p < 0.001). Additionally, 3.4% of patients (five of 148) achieved complete pathological remission, though investigators noted this relatively low rate may be attributed to the limited neoadjuvant treatment duration of two cycles.
Safety Profile Supports Clinical Feasibility
The safety profile demonstrated the feasibility of this perioperative approach, with a discontinuation rate of only 8%. Grade 3 and above treatment-related adverse events occurred in 37.6% of patients receiving the combination, with hypertension and hepatotoxicity being the most common. These findings suggest limited safety concerns and support the regimen's feasibility in the perioperative setting.
Scientific Rationale and Previous Success
The decision to evaluate this combination in the perioperative setting was supported by strong efficacy data in advanced disease. In a Phase III trial for unresectable HCC (搜索), the camrelizumab and rivoceranib combination, which is approved in China, improved overall survival to 22.1 months compared with 15.2 months with sorafenib (hazard ratio 0.62; 95% CI 0.49-0.80). This demonstrated synergistic efficacy provided the rationale for bringing the immunotherapy/anti-angiogenic combination into earlier, curative settings.
Market Impact and Global Implications
The results have significant commercial implications, particularly given China's dominance in the global HCC (搜索) market, accounting for more than 50% of worldwide cases. The findings strengthen Jiangsu Hengrui (搜索)'s position in the Chinese HCC market and expand the potential of both camrelizumab and rivoceranib beyond advanced disease applications.
While rapid adoption is expected in China where both agents are already marketed, global expansion will depend on ongoing FDA review and harmonization with Western regulatory standards. Despite receiving a second complete response letter for advanced HCC (搜索) treatment in March 2025, these perioperative efficacy results could revitalize confidence in Hengrui (搜索)'s immuno-oncology pipeline in Western markets.
Future Implications for HCC Treatment
Overall survival data remains immature, with only 39 events observed at this interim analysis. However, if the perioperative indication secures regulatory approval, it could differentiate the camrelizumab plus rivoceranib regimen from other PD-1 (搜索)/VEGF (搜索) combinations that remain limited to advanced settings. Confirmed with mature OS data, CARES-009 could establish perioperative PD-1 plus VEGFR inhibition as a new global standard of care, fundamentally reshaping the HCC (搜索) treatment paradigm and expanding the immuno-oncology footprint in early-stage disease.