Immune checkpoint inhibitor–based combinations have changed the treatment paradigm for advanced HCC [59,60] and are likely to remain the cornerstone of systemic treatment in the next few years.
基于免疫检查点抑制剂的联合治疗已经改变了晚期HCC[59,60]的治疗模式，并有可能在未来几年继续保持全身治疗的基石。 The IMbrave150 trial compared treatment with atezolizumab plus bevacizumab and treatment with sorafenib; they reported an impressive ORR of 30% and an unprecedented OS benefit for the combination treatment over sorafenib (median survival, 19.2 vs. 13.4 months, HR 0.66) [60,61]. IMbrave150试验比较了阿替唑珠单抗联合贝伐单抗和索拉非尼治疗；他们报告了联合治疗比索拉非尼的ORR和前所未有的OS获益(中位生存期，19.2vs.13.4个月，HR0.66)[60,61]。 Several ongoing Phase 3 trials testing immune checkpoint inhibitors in combinations with other immuno-oncology agents or multikinase inhibitors (MKIs) are ongoing.
一些正在进行的3期临床试验正在测试免疫检查点抑制剂与其他免疫肿瘤药物或多激酶抑制剂(MKIs)联合使用。
Chemotherapeutic modalities have been proved to be synergistic with anti-PD1/PD-L1 antibodies in several cancers, such as those of the lung and breast [62,63].
化疗方式已被证明与抗pd1/PD-L1抗体在几种癌症中具有协同作用，如肺癌和乳腺[62,63]。 HAIC may also induce substantial local immune modulation in the intrahepatic tumor microenvironment of HCC. Whether HAIC plus PD1/PD-L1 blockade would have synergistic effects warrants further investigations. Preliminary results of early phase trials of PD-1 blockade plus MKIs have been promising [59], and investigations of triplet therapy, namely anti-PD-1, MKIs, and HAIC, are ongoing. HAIC也可能在HCC的肝内肿瘤微环境中诱导大量的局部免疫调节。HAIC+PD1/PD-L1阻断是否具有协同作用，有待进一步研究。PD-1阻断+MKIs的早期试验的初步结果是很有希望的[59]，而三联体疗法的研究，即抗PD-1、MKIs和HAIC的研究正在进行中。 Gu et al. [49] reported a single-center experience for six patients who received HAIC combined with apatinib and toripalimab as the first-line treatment for advanced HCC. All six patients responded to treatment (ORR, 100%), and three of the patients (50%) exhibited complete responses. 顾等人。[49]报道了6例接受HAIC联合阿帕替尼和托帕利马抗作为晚期HCC一线治疗的患者的单中心经验。所有6例患者对治疗均有反应(ORR，100%)，其中3例患者（50%）表现出完全缓解。 He et al. [50] presented a retrospective study in which 71 patients underwent treatment involving a combination of HAIC, lenvatinib, and toripalimab; they reported a high ORR (59%) after treatment. These encouraging results support further research on HAIC combined with other immune-based therapeutic agents.
何等人。[50]提出了一项回顾性研究，71例患者接受了HAIC、与伐替尼和托帕单抗联合治疗；他们报告治疗后高ORR（59%）。这些令人鼓舞的结果支持了对HAIC与其他免疫基治疗药物联合使用的进一步研究。
In summary, many studies have shown positive signs for HAIC combination treatments. In particular, for patients with major PVT, HAIC plus sorafenib provided a longer OS [45,47]. Regarding the combination of HAIC with other therapeutic modalities, HAIC plus RT or PD-1/PD-L1 blockade also demonstrated promising results [49,50,52,53,54]. We believe these HAIC-based combination treatments will become the dominant trend in clinical practice and clinical trials.
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