Discussion
HBV infection, BCLC, PVTT, malignancies, HCC, tumors
MALIGNANCIES, DISEASE, TUMORS
The therapeutic landscape of HCC has undergone significant advancements with the integration of antiangiogenic agents and immunotherapy. As demonstrated in the IMbrave150 study, atezolizumab and bevacizumab achieved an ORR of 27.3% and a median PFS spanning 6.8 months for HCC.The prognosis of HCC patients with high-risk features remains suboptimal. Our study also enrolled patients at high-risk, including eight patients with Vp 4 PVTT and 21 with tumors larger than 10 cm. According to the subgroup analysis, the combination of camrelizumab, apatinib and HAIC-FOLFOX yielded high response rate for these patients. Notably, one patient who initially met the inclusion criteria with an ECOG PS score of 1 experienced a deterioration to 2 before treatment. Despite this, the patient showed improvement in ECOG PS score and achieved a PR after treatment. This observation suggests that the regimen may extend benefits to patients with poorer ECOG PS scores, although further research is needed to confirm this. Consistent with our results, Lai et al. also demonstrated that combining HAIC-FOLFOX with lenvatinib and toripalimab is a viable option for HCC patients exhibiting high-risk characteristics.After the triple combination treatment, six patients (17.1%) achieved disease downstaging and received curative therapy, including five patients who underwent R0 resection, and one patient who received curative ablation. This advantage has also been discussed in several other studies about HAIC. According to a study in patients with large HCC, a notably increased rate of curative surgical resection was evident in the HAIC-FOLFOX group compared to the TACE group (24% vs. 12%).The QoL of patients with malignancies are of paramount importance, particularly since it is proven to affect the long-term prognosis of the patients.In our findings, the combination of HAIC with camrelizumab and apatinib was generally well-tolerated. The frequency and severity of AEs encountered in our cohort aligned with the established safety profiles of HAIC and the combination of camrelizumab and apatinib, as indicated in prior research.This trial is not without its limitations. First, the lack of a control arm in our single-arm design makes it difficult to definitively attribute the observed benefits solely to the addition of systemic therapy following HAIC. Second, the study’s sample size was limited, and although we met the predetermined criteria of Simon’s two-stage design, early termination of the study could potentially result in an overestimation of the ORR. To comprehensively evaluate the merits of the triple combination, we have initiated a randomized controlled phase 3 trial (NCT05313282) aimed at assessing its benefit compared to camrelizumab plus apatinib in HCC patients with BCLC Stage C. Third, the study exclusively enrolled patients with HBV infection, representing 85–90% of HCC cases in China.In summary, the regimen combining camrelizumab, apatinib, and HAIC demonstrated efficacy and safety in treating BCLC stage C HCC patients. Conclusions with more powerful evidence may be obtained from the phase 3 study in the near future.