Abstract：
To report long-term efficacy and safety of selinexor maintenance therapy in adults with TP53 wild-type (TP53wt) stage IV or recurrent endometrial cancer (EC) who achieved partial remission (PR) or complete remission (CR) following chemotherapy.
Analysis of the prespecified, exploratory subgroup of patients with TP53wt EC from the phase 3 SIENDO study was performed. Progression-free survival (PFS) benefit in patients with TP53wt EC and across other patient subgroups were exploratory endpoints. Safety and tolerability were also assessed.
Of the 263 patients enrolled in the SIENDO trial, 113 patients had TP53wt EC; 70/113 (61.9%) had TP53wt/proficient mismatch repair (pMMR) EC, and 29/113 (25.7%) had TP53wt/deficient mismatch repair (dMMR) EC. As of April 1, 2024, the median PFS (mPFS) for TP53wt patients who received selinexor compared with placebo was 28.4 versus 5.2 months (36.8-month follow-up, HR 0.44; 95% CI 0.27-0.73). A benefit in mPFS was seen with selinexor versus placebo regardless of MMR status (patients with TP53wt/pMMR EC: 39.5 vs 4.9 months, HR 0.36; 95% CI 0.19-0.71; patients with TP53wt/dMMR EC: 13.1 vs 3.7 months, HR 0.49; 95% CI 0.18-1.34). Selinexor treatment was generally manageable, with no new safety signals identified.
In the phase 3 SIENDO study, selinexor maintenance therapy showed a promising efficacy signal and a manageable safety profile in the prespecified subgroup of patients with TP53wt EC who achieved a PR or CR following chemotherapy. These results are being further evaluated in an ongoing randomized phase 3 trial (NCT05611931).
Analysis of the prespecified, exploratory subgroup of patients with TP53wt EC from the phase 3 SIENDO study was performed. Progression-free survival (PFS) benefit in patients with TP53wt EC and across other patient subgroups were exploratory endpoints. Safety and tolerability were also assessed.
Of the 263 patients enrolled in the SIENDO trial, 113 patients had TP53wt EC; 70/113 (61.9%) had TP53wt/proficient mismatch repair (pMMR) EC, and 29/113 (25.7%) had TP53wt/deficient mismatch repair (dMMR) EC. As of April 1, 2024, the median PFS (mPFS) for TP53wt patients who received selinexor compared with placebo was 28.4 versus 5.2 months (36.8-month follow-up, HR 0.44; 95% CI 0.27-0.73). A benefit in mPFS was seen with selinexor versus placebo regardless of MMR status (patients with TP53wt/pMMR EC: 39.5 vs 4.9 months, HR 0.36; 95% CI 0.19-0.71; patients with TP53wt/dMMR EC: 13.1 vs 3.7 months, HR 0.49; 95% CI 0.18-1.34). Selinexor treatment was generally manageable, with no new safety signals identified.
In the phase 3 SIENDO study, selinexor maintenance therapy showed a promising efficacy signal and a manageable safety profile in the prespecified subgroup of patients with TP53wt EC who achieved a PR or CR following chemotherapy. These results are being further evaluated in an ongoing randomized phase 3 trial (NCT05611931).
摘要：
目的：报告Selinexor维持治疗在TP53野生型（TP53wt）IV期或复发性子宫内膜癌（EC）患者化疗后部分缓解（PR）或完全缓解（CR）中的长期疗效和安全性。
方法：分析预先指定的，对来自SIENDO3期研究的TP53wtEC患者进行探索性亚组.TP53wtEC患者和其他患者亚组的无进展生存期（PFS）获益是探索性终点。还评估了安全性和耐受性。
结果：在SIENDO试验的263名患者中，113例患者有TP53wtEC;70/113(61.9%)有TP53wt/精通错配修复(pMMR)EC,29/113（25.7%）患有TP53wt/缺陷性错配修复（dMMR）EC。截至2024年4月1日，与安慰剂相比，接受selinexor的TP53wt患者的中位PFS（mPFS）为28.4和5.2个月（随访36.8个月，HR0.44；95%CI0.27-0.73）。无论MMR状态如何，selinexor与安慰剂相比，mPFS均有益处（TP53wt/pMMREC患者：39.5对4.9个月，HR0.36；95%CI0.19-0.71；TP53wt/dMMREC患者：13.1vs3.7个月，HR0.49；95%CI0.18-1.34）。Selinexor治疗通常是可控的，没有发现新的安全信号。
结论：在第3阶段SIENDO研究中，在化疗后达到PR或CR的TP53wtEC患者的预设亚组中,selinexor维持治疗显示了有希望的疗效信号和可控的安全性.这些结果正在一项正在进行的随机3期试验(NCT05611931)中进一步评估。
方法：分析预先指定的，对来自SIENDO3期研究的TP53wtEC患者进行探索性亚组.TP53wtEC患者和其他患者亚组的无进展生存期（PFS）获益是探索性终点。还评估了安全性和耐受性。
结果：在SIENDO试验的263名患者中，113例患者有TP53wtEC;70/113(61.9%)有TP53wt/精通错配修复(pMMR)EC,29/113（25.7%）患有TP53wt/缺陷性错配修复（dMMR）EC。截至2024年4月1日，与安慰剂相比，接受selinexor的TP53wt患者的中位PFS（mPFS）为28.4和5.2个月（随访36.8个月，HR0.44；95%CI0.27-0.73）。无论MMR状态如何，selinexor与安慰剂相比，mPFS均有益处（TP53wt/pMMREC患者：39.5对4.9个月，HR0.36；95%CI0.19-0.71；TP53wt/dMMREC患者：13.1vs3.7个月，HR0.49；95%CI0.18-1.34）。Selinexor治疗通常是可控的，没有发现新的安全信号。
结论：在第3阶段SIENDO研究中，在化疗后达到PR或CR的TP53wtEC患者的预设亚组中,selinexor维持治疗显示了有希望的疗效信号和可控的安全性.这些结果正在一项正在进行的随机3期试验(NCT05611931)中进一步评估。
