Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China.
State Key Laboratory of Oncology in South China, Guangzhou, China.
BMC Cancer. 2023 Feb 10;23(1):145. doi: 10.1186/s12885-023-10613-y.
Overall survival (OS) is the gold standard to assess novel therapeutics to treat cancer. However, to identify early efficacy and speed up drug approval, trials have used progression-free survival (PFS) as a surrogate endpoint (SE). Herein, we aimed to examine if PFS could function as an OS surrogate in advanced Esophageal Squamous Cell Carcinoma (ESCC) treated with first-line immunochemotherapy.
Two hundred ninety-two advanced ESCC patients treated using inhibitors of PD-1/PD-L1 + chemotherapy or chemotherapy alone were collected. In addition, six phase III randomized clinical trials were eligible for inclusion. Bayesian normal-induced-copula-estimation model in retrospective patient data and regression analysis in the published trial data were used to determine the PFS-OS correlation.
PFS correlated moderately with OS in the retrospective cohort (Kendall's Tau = 0.684, τ = 0.436). In trial-level, treatments effects for PFS correlated weakly with those for OS in intention-to-treat population (R = 0.436, adj.R = 0.249, P > 0.05) and in PD-L1-enriched population (R = 0.072). In arm-level, median PFS also correlated weakly with median OS. Moreover, analysis of the retrospective cohort demonstrated that the annual death risk after progression in the continued immunotherapy group was considerably lower than that in the discontinued group.
In trials of anti-PD-1 agents to treat advanced ESCC, the current results provide only weak support for PFS as an OS surrogate; OS cannot be substituted completely by PFS in these cases. The results also suggest that qualified patients with advanced ESCC might benefit from continuous immunotherapy beyond progression to achieve a decreased risk of death.
总生存期（OS）是评估癌症治疗新疗法的金标准。然而，为了早期评估疗效并加速药物审批，试验已经将无进展生存期（PFS）作为替代终点（SE）。在此，我们旨在研究在接受一线免疫化疗治疗的晚期食管鳞状细胞癌（ESCC）患者中，PFS 是否可以作为 OS 的替代指标。
收集了 292 例接受 PD-1/PD-L1 抑制剂+化疗或单独化疗治疗的晚期 ESCC 患者。此外，有 6 项 III 期随机临床试验符合纳入标准。采用贝叶斯正态诱导 Copula 估计模型对回顾性患者数据进行分析，并对已发表试验数据进行回归分析，以确定 PFS 与 OS 的相关性。
回顾性队列中 PFS 与 OS 中度相关（Kendall's Tau=0.684，τ=0.436）。在试验水平，意向治疗人群中 PFS 的治疗效果与 OS 的治疗效果弱相关（R=0.436，adj.R=0.249，P>0.05），在 PD-L1 富集人群中也弱相关（R=0.072）。在治疗组水平，中位 PFS 与中位 OS 也弱相关。此外，回顾性队列分析表明，在继续接受免疫治疗组中，进展后每年的死亡风险明显低于中断组。
在抗 PD-1 药物治疗晚期 ESCC 的试验中，目前的结果仅为 PFS 作为 OS 替代指标提供了较弱的支持；在这些情况下，OS 不能完全被 PFS 替代。这些结果还表明，符合条件的晚期 ESCC 患者在进展后继续接受免疫治疗可能会降低死亡风险，从而获益。
