Supplementary Material for: Clinical Impact of Early Tumour Shrinkage in Metastatic or Unresectable Oesophageal Cancer Treated with Pembrolizumab plus Chemotherapy

Introduction: Metastatic or unresectable locally advanced oesophageal cancer remains a disease with high mortality. More recently, pembrolizumab plus chemotherapy has been indicated as the first-line treatment for those patients, but the predictive factors for treatment efficacy remain controversial. This study investigated the clinical utility of early tumour shrinkage (ETS) and depth of response (DpR) in metastatic or unresectable oesophageal cancer treated with pembrolizumab plus CF therapy. Methods: ETS and DpR, defined as the percent decreases at the second evaluation and the percentage of the maximal tumour shrinkage during treatment, were measured in 53 eligible patients. The ETS and DpR cut-off values were 20% and 30%, respectively, based on survival outcomes. Results: Twenty-seven patients (51%) were treatment-naïve, while 26 (49%) had received any treatment before initiating pembrolizumab plus CF therapy. The median progression-free survival (PFS) and overall survival (OS) for ETS ≥20% and <20% were 12.7 and 5.5 months and 14.4 and 8.2 months, and 12.7 and 4.9 months and 14.4 and 8.0 months for DpR ≥30% and <30%, respectively. ETS <20% showed early tumour growth, whereas ETS ≥20% had a good response rate with sufficient longer response duration. In addition, an ETS cut-off of 20% predicted the best overall response and was not associated with prior treatment. In multivariable analysis, ETS ≥20% and DpR ≥30% were independent factors of longer PFS. Conclusion: Our findings suggest that an ETS is a promising on-treatment marker for early prediction of further sensitivity to pembrolizumab plus CF therapy.

引言：转移性或不可切除的局部晚期食管癌仍是一类高致死性疾病。近年来，帕博利珠单抗（pembrolizumab）联合化疗已被推荐作为此类患者的一线治疗方案，但治疗疗效的预测因子仍存在争议。本研究探讨了接受帕博利珠单抗联合CF方案治疗的转移性或不可切除食管癌患者中，早期肿瘤退缩（early tumour shrinkage, ETS）与应答深度（depth of response, DpR）的临床应用价值。
方法：本研究对53例符合入组标准的患者进行了评估，其中ETS定义为第二次评估时的肿瘤退缩百分比，DpR定义为治疗期间最大肿瘤退缩的百分比。基于生存结局，ETS和DpR的截断值分别设定为20%和30%。
结果：53例患者中，27例（51%）为初治患者，26例（49%）在接受帕博利珠单抗联合CF方案治疗前曾接受过其他治疗。对于ETS≥20%与ETS<20%的患者，中位无进展生存期（progression-free survival, PFS）与总生存期（overall survival, OS）分别为12.7个月、5.5个月和14.4个月、8.2个月；对于DpR≥30%与DpR<30%的患者，中位PFS与OS分别为12.7个月、4.9个月和14.4个月、8.0个月。ETS<20%的患者早期出现肿瘤进展，而ETS≥20%的患者应答率更佳，且应答持续时间显著更长。此外，ETS截断值20%可预测最佳总体应答，且与既往治疗史无关。多变量分析显示，ETS≥20%与DpR≥30%均为更长PFS的独立预测因子。
结论：本研究结果表明，ETS可作为一种极具潜力的治疗期间标志物，用于早期预测患者对帕博利珠单抗联合CF方案治疗的后续敏感性。