Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, QC, Canada.
Kite, a Gilead Company, Gilead Sciences International Ltd, 2 Roundwood Ave, Hayes, Uxbridge UB11 1AF, UK.
Crit Rev Oncol Hematol. 2022 Jul;175:103711. doi: 10.1016/j.critrevonc.2022.103711. Epub 2022 May 16.
Event-free survival (EFS) is increasingly used as a primary endpoint in trials of haematological malignancies (HMs). A key consideration is whether EFS can reliably predict survival.
We conducted a review of the scientific literature and health technology assessments to evaluate evidence for EFS-OS surrogacy in HMs and acceptability of EFS by payers.
Evidence of surrogacy varies by indication and line of therapy. In first-line AML, EFS is highly correlated with OS at the trial-level supporting its use as an early endpoint for traditional approval of treatments with curative intent. Surrogacy was also demonstrated in first-line DLBCL but remains unexplored in relapsed/refractory setting where post-transplant EFS24 was not prognostic of survival. In first-line FL, PTCL, T-LBL, and MCL, EFS24 is prognostic of survival but trial-level surrogacy has not yet been evaluated.
Strong EFS-OS correlation required for surrogacy may only be achievable in HMs with treatments characterised by high rates of durable remissions. Nevertheless, EFS24 is associated with favourable outcomes and remains a clinically meaningful endpoint in HMs.
无事件生存（EFS）越来越多地被用作血液恶性肿瘤（HMs）试验的主要终点。一个关键的考虑因素是 EFS 是否能够可靠地预测生存。
我们对科学文献和卫生技术评估进行了综述，以评估在 HMs 中 EFS 与 OS 替代的证据以及 EFS 在支付方中的可接受性。
替代证据因适应症和治疗线而异。在一线 AML 中，EFS 与 OS 在试验水平上高度相关，支持将其用作具有治愈意图的治疗传统批准的早期终点。在一线 DLBCL 中也证明了替代关系，但在复发/难治性环境中仍未得到探索，其中移植后 EFS24 不能预测生存。在一线 FL、PTCL、T-LBL 和 MCL 中，EFS24 与生存相关，但尚未评估试验水平的替代关系。
替代关系所需的 EFS-OS 强相关性可能仅在治疗后持久缓解率高的血液恶性肿瘤中才能实现。尽管如此，EFS24 与良好的结果相关，并且在血液恶性肿瘤中仍然是一个有临床意义的终点。
