Background:Advanced adrenocortical carcinoma (ACC) remains a challenging malignancy with limited therapeutic options. Multi-kinase inhibitors (MKIs), either alone or in combination with immuno-oncology (IO) agents, have been investigated in recent single-arm clinical trials and retrospective series.Methods:We conducted a systematic review and single-arm meta-analysis of studies evaluating MKIs in advanced ACC. Objective response rate (ORR) and disease control rate (DCR) were pooled using random-effects models for single-arm proportions. Overall survival (OS) and progression-free survival (PFS) were summarized descriptively due to limited variance data. Subgroup analyses compared MKI monotherapy versus MKI + IO combinations, and meta-regression was performed to assess the impact of prior mitotane exposure.Results:Eleven studies (n= 208 patients) were included. The pooled ORR was 21% (95%CI, 11–36%), and the DCR was approximately 57%. Subgroup analysis revealed a higher ORR with MKI + IO regimens (26%; 95%CI, 12–48%) compared to MKI monotherapy (15%; 95%CI, 3–47%). Median OS ranged from 5.4 to 30.6 months, and PFS from 2.8 to 13.3 months, both favouring MKI + IO combinations. Meta-regression identified prior mitotane exposure as a significant predictor of ORR (p= 0.0279), particularly within the MKI + IO subgroup.Conclusions:MKI-based regimens, especially when combined with IO, demonstrate promising efficacy in advanced ACC, a disease with few established second-line options. While limited by the non-comparative design of available studies, these findings support further investigation in prospective, randomized clinical trials.
背景：晚期肾上腺皮质癌（ACC）是一种治疗选择有限的难治性恶性肿瘤。近年来，多项单臂临床试验及回顾性研究对多激酶抑制剂（MKIs）单药或联合免疫肿瘤（IO）药物的治疗方案进行了探索。 方法：我们对评估MKIs治疗晚期ACC的研究进行了系统性综述与单臂荟萃分析。采用随机效应模型对单臂比例数据进行汇总，计算客观缓解率（ORR）与疾病控制率（DCR）。由于方差数据有限，总生存期（OS）与无进展生存期（PFS）采用描述性总结。通过亚组分析比较MKI单药与MKI联合IO方案的疗效，并采用荟萃回归分析评估既往米托坦暴露对疗效的影响。 结果：共纳入11项研究（208例患者）。汇总ORR为21%（95%CI：11-36%），DCR约为57%。亚组分析显示，MKI联合IO方案的ORR（26%；95%CI：12-48%）高于MKI单药治疗（15%；95%CI：3-47%）。中位OS范围为5.4至30.6个月，中位PFS范围为2.8至13.3个月，两项指标均显示MKI联合IO方案更具优势。荟萃回归分析证实既往米托坦暴露是ORR的显著预测因素（p=0.0279），尤其在MKI联合IO亚组中更为明显。 结论：基于MKI的治疗方案，特别是联合IO药物时，在缺乏成熟二线治疗选择的晚期ACC中展现出具有前景的疗效。尽管现有研究的非对照设计存在局限性，这些发现仍支持在前瞻性随机临床试验中开展进一步研究。
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