Researchers from a recent phase II clinical trial have reported that the combination of hepatic arterial infusion chemotherapy (HAIC) with FOLFOX plus camrelizumab and sorafenib showed modest antitumor activity in patients with Barcelona Clinic Liver Cancer (BCLC) stage C advanced hepatocellular carcinoma (HCC).
The single-arm phase II trial, registered as ChiCTR2100041874, failed to meet its primary endpoint of objective response rate (ORR), with the study terminating after the first stage of Simon's two-stage design.
Study Design and Treatment Protocol
The trial enrolled 25 patients with BCLC stage C HCC between January 2021 and December 2023. Patients received up to six 21-day cycles of hepatic artery infusion with FOLFOX chemotherapy (oxaliplatin, fluorouracil, and leucovorin) plus camrelizumab (200 mg once every 3 weeks). Sorafenib (400 mg orally twice daily) was administered beginning on day 3 after the first cycle of hepatic arterial infusion until disease progression, intolerable toxicity, or conversion to surgical resection.
The patient population included predominantly males (96.0%) with hepatitis B virus infection (92.0%), large tumor size (≥10 cm; 60.0%), multiple intrahepatic tumors (≥4, 80.0%), and portal vein tumor thrombosis (72.0%).
Efficacy Outcomes
According to the modified Response Evaluation Criteria in Solid Tumors (mRECIST), 11 patients achieved partial response, resulting in an ORR of 44.0% (95% CI, 24.6–63.5%). This fell short of the predetermined threshold of 48% needed to proceed to the second stage of the trial.
"The primary endpoint was not met, and the study failed to enter the second stage," the researchers noted.
Other efficacy outcomes included:
- Median progression-free survival: 4.87 months (95% CI, 2.07–7.66)
- Median overall survival: 8.87 months (95% CI, 8.17–9.57)
- 12-month overall survival rate: 40.3%
- 24-month overall survival rate: 26.9%
Only two patients (8.0%) were able to receive curative resection after the study treatment.
Safety Profile
The treatment combination demonstrated a manageable safety profile, though treatment-related adverse events (TRAEs) were common. Grade ≥3 TRAEs occurred in 19 patients (76.0%), with the most frequent being:
- Decreased lymphocyte count: 13 patients (52.0%)
- Increased aspartate aminotransferase: 11 patients (44.0%)
- Increased alanine aminotransferase: 7 patients (28.0%)
Notably, reactive cutaneous capillary endothelial proliferation, a known side effect of camrelizumab, was observed in only one patient (4.0%) and was mild. No patients experienced immune-related serious adverse events, and no treatment-related deaths were reported.
Comparison with Other Approaches
The researchers compared their findings with previous studies, noting that the combination of HAIC with FOLFOX regimen, intravenous camrelizumab, and oral apatinib had shown significantly better results in other trials, with ORRs reaching up to 88.6%.
"The differences in ORR between this study and other studies may be explained by several possible reasons," the authors explained. "First, the efficacy of apatinib is significantly better than sorafenib, and previous phase 3 CARES-310 study proved that the combination of camrelizumab and apatinib had a synergistic antitumor effect in the treatment of advanced HCC."
Promising Alternative: HAIC with Camrelizumab and Apatinib
In a parallel single-arm exploratory trial (NCT05099848) also reported recently, researchers investigated HAIC combined with camrelizumab and apatinib as conversion therapy for unresectable HCC.
This study showed more promising results, with 14 of 19 patients (73.7%) becoming eligible for curative surgery after conversion therapy. Nine patients (47.4%) received R0 resection, while five refused surgery and opted for observation. Three of the nine surgical patients achieved major pathological response, including two with pathological complete response.
The objective response rate in this trial was 47.4% per RECIST 1.1 and 89.5% per mRECIST. The 1-year and 2-year progression-free survival rates were 63.2% and 55.3%, while the 1-year and 2-year overall survival rates were 73.7% and 63.2%, respectively.
Clinical Implications
These findings suggest that while the combination of HAIC with FOLFOX plus camrelizumab and sorafenib has limited efficacy in advanced HCC, the alternative approach using HAIC with camrelizumab and apatinib shows more promise, particularly as conversion therapy to enable surgical resection.
"Although this regimen cannot be recommended as standard of care, our results suggest that for patients who are willing to incorporate immunotherapy into the treatment, our treatment regimen maybe an alternative option," the researchers concluded. "Further optimization of drug combinations or dosing strategies is required to further improve the current regimen."
The researchers also noted that the route of administration for immunotherapy agents may be important, suggesting that intravenous administration of PD-1 inhibitors might be superior to arterial administration for activating immune cells in peripheral blood.
Both studies highlight the ongoing efforts to improve outcomes for patients with advanced HCC through novel combination approaches and emphasize the need for further research to optimize treatment strategies for this challenging disease.
