Supplementary Material for: Objective response and progression free survival contribute to prolong overall survival in atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma.

Introduction: Atezolizumab plus bevacizumab (Atez/Bev) is a standard treatment for unresectable hepatocellular carcinoma (HCC) due to its good anti-tumor and survival prolongation effects. Post-progression survival (PPS) has been reported to be a great contributor in the treatment with tyrosine kinase inhibitors for unrecetable HCC. This study aimed to clarify the significance of progression-free survival (PFS) or PPS of Atez/Bev treatment for HCC. Methods: We analyzed the correlations of PFS and PPS with overall survival (OS) in studies of HCC patients treated with Atez/Bev and evaluated the contribution to OS in Atez/Bev treatment with patients at our institutions as clinical practice. Results: Analysis of 18 studies involving 2,937 patients treated with Atez/Bev found that PPS had a stronger correlation with OS (R2=0.872, p<0.001) than did PFS (R2=0.605, p=0.001). Analysis of 80 patients with unresectable HCC treated with Atez/Bev found that presence of anti-tumor responses during Atez/Bev was the most significant contributor to OS, and post-progression treatment after Atez/Bev also significantly contribute to OS. Conclusion: The presence of anti-tumor response with tumor shrinkage during Atez/Bev treatment contributes to good OS through its durable response. Atez/Bev treatment could be considered as first-line treatment for unresectable HCC. However, there is a need for optimal biomarkers for good-anti-tumor response.

引言：阿替利珠单抗（Atezolizumab）联合贝伐珠单抗（bevacizumab，简称Atez/Bev）因具备优异的抗肿瘤活性与生存延长获益，是不可切除肝细胞癌（unresectable hepatocellular carcinoma, HCC）的标准治疗方案。已有研究表明，进展后生存（post-progression survival, PPS）在酪氨酸激酶抑制剂（tyrosine kinase inhibitors）治疗不可切除肝细胞癌的方案中是重要的预后影响因素。本研究旨在明确Atez/Bev方案治疗肝细胞癌时，无进展生存（progression-free survival, PFS）与进展后生存（PPS）的临床意义。方法：本研究分析了接受Atez/Bev治疗的肝细胞癌患者相关临床研究中，PFS、PPS与总生存（overall survival, OS）的相关性，并结合本中心临床实践队列的患者数据，评估了Atez/Bev治疗各因素对OS的贡献度。结果：对18项纳入2937例接受Atez/Bev治疗患者的研究进行分析后发现，PPS与OS的相关性（决定系数R²=0.872，p<0.001）显著优于PFS（R²=0.605，p=0.001）。对本中心80例接受Atez/Bev治疗的不可切除肝细胞癌患者进行分析后显示，Atez/Bev治疗期间出现抗肿瘤应答是影响OS的最显著独立因素，且Atez/Bev治疗进展后的后续治疗同样对OS具有显著贡献。结论：Atez/Bev治疗期间出现伴随肿瘤缩小的抗肿瘤应答，可通过持久的抗肿瘤效应改善患者总生存。Atez/Bev可作为不可切除肝细胞癌的一线治疗方案，但仍需筛选可预测良好抗肿瘤应答的优化生物标志物。