Abstract：
BACKGROUND: Immunotherapy has transformed the endometrial cancer treatment landscape, particularly for those exhibiting mismatch repair deficiency [MMRd/microsatellite instability-hypermutated (MSI-H)]. A growing body of evidence supports the integration of immunotherapy with chemotherapy as a first-line treatment strategy. Recently, findings from ongoing trials such as RUBY (NCT03981796), NRG-GY018 (NCT03914612), AtTEnd (NCT03603184), and DUO-E (NCT04269200) have been disclosed.
METHODS: This paper constitutes a review and meta-analysis of phase III trials investigating the role of immunotherapy in the first-line setting for advanced or recurrent endometrial cancer.
RESULTS: The pooled data from 2320 patients across these trials substantiate the adoption of chemotherapy alongside immunotherapy, revealing a significant improvement in progression-free survival compared to chemotherapy alone [hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.62-0.79] across all patient groups. Progression-free survival benefits are more pronounced in MMRd/MSI-H tumors (n = 563; HR 0.33, 95% CI 0.23-0.43). This benefit, albeit less robust, persists in the MMR-proficient/microsatellite stable group (n = 1757; HR 0.74, 95% CI 0.60-0.91). Pooled data further indicate that chemotherapy plus immunotherapy enhances overall survival compared to chemotherapy alone in all patients (HR 0.75, 95% CI 0.63-0.89). However, overall survival data maturity remains low.
CONCLUSIONS: The incorporation of immunotherapy into the initial treatment for advanced and metastatic endometrial cancer brings about a substantial improvement in oncologic outcomes, especially within the MMRd/MSI-H subset. This specific subgroup is currently a focal point of investigation for evaluating the potential of chemotherapy-free regimens. Ongoing exploratory analyses aim to identify non-responding patients eligible for inclusion in clinical trials.
METHODS: This paper constitutes a review and meta-analysis of phase III trials investigating the role of immunotherapy in the first-line setting for advanced or recurrent endometrial cancer.
RESULTS: The pooled data from 2320 patients across these trials substantiate the adoption of chemotherapy alongside immunotherapy, revealing a significant improvement in progression-free survival compared to chemotherapy alone [hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.62-0.79] across all patient groups. Progression-free survival benefits are more pronounced in MMRd/MSI-H tumors (n = 563; HR 0.33, 95% CI 0.23-0.43). This benefit, albeit less robust, persists in the MMR-proficient/microsatellite stable group (n = 1757; HR 0.74, 95% CI 0.60-0.91). Pooled data further indicate that chemotherapy plus immunotherapy enhances overall survival compared to chemotherapy alone in all patients (HR 0.75, 95% CI 0.63-0.89). However, overall survival data maturity remains low.
CONCLUSIONS: The incorporation of immunotherapy into the initial treatment for advanced and metastatic endometrial cancer brings about a substantial improvement in oncologic outcomes, especially within the MMRd/MSI-H subset. This specific subgroup is currently a focal point of investigation for evaluating the potential of chemotherapy-free regimens. Ongoing exploratory analyses aim to identify non-responding patients eligible for inclusion in clinical trials.
摘要：
背景：免疫治疗改变了子宫内膜癌治疗领域，特别是那些表现出错配修复缺陷（MMRd/MSI-H）。越来越多的证据支持将免疫治疗与化疗整合作为一线治疗策略。最近,来自正在进行的试验的结果，如RUBY(NCT03981796)，NRG-GY018(NCT03914612),AtTEnd(NCT03603184),和DUO-E(NCT04269200)已经被公开。
方法：本文对研究免疫治疗在晚期或复发性子宫内膜癌一线治疗中的作用的III期试验进行综述和荟萃分析。
结果：这些试验的2,320名患者的汇总数据证实了化疗和免疫疗法的采用。在所有患者组中,与单纯化疗相比,无进展生存期显著改善(危险比(HR):0.70,95%置信区间(CI):0.62,0.79).无进展生存获益在MMRd/MSI-H肿瘤中更为显著(n=563;HR:0.33,95%CI:0.23,0.43)。这个好处,尽管不那么健壮，MMRp/MSS组仍然存在（n=1,757；HR：0.74，95％CI：0.60，0.91）。汇总数据进一步表明，与单独化疗相比，化疗加免疫治疗可提高所有患者的总生存率（HR：0.75，95％CI：0.63，0.89）。然而,总体生存数据成熟度仍然很低.
结论：在晚期和转移性子宫内膜癌的初始治疗中加入免疫疗法可以显著改善肿瘤预后。特别是在MMRd/MSI-H子集内。该特定亚组目前是评估无化疗方案潜力的研究重点。正在进行的探索性分析旨在确定有资格纳入临床试验的无反应患者。
方法：本文对研究免疫治疗在晚期或复发性子宫内膜癌一线治疗中的作用的III期试验进行综述和荟萃分析。
结果：这些试验的2,320名患者的汇总数据证实了化疗和免疫疗法的采用。在所有患者组中,与单纯化疗相比,无进展生存期显著改善(危险比(HR):0.70,95%置信区间(CI):0.62,0.79).无进展生存获益在MMRd/MSI-H肿瘤中更为显著(n=563;HR:0.33,95%CI:0.23,0.43)。这个好处,尽管不那么健壮，MMRp/MSS组仍然存在（n=1,757；HR：0.74，95％CI：0.60，0.91）。汇总数据进一步表明，与单独化疗相比，化疗加免疫治疗可提高所有患者的总生存率（HR：0.75，95％CI：0.63，0.89）。然而,总体生存数据成熟度仍然很低.
结论：在晚期和转移性子宫内膜癌的初始治疗中加入免疫疗法可以显著改善肿瘤预后。特别是在MMRd/MSI-H子集内。该特定亚组目前是评估无化疗方案潜力的研究重点。正在进行的探索性分析旨在确定有资格纳入临床试验的无反应患者。
