Recurrent Endometrial Cancer Research Articles

Real world outcomes in patients with recurrent, advanced, or metastatic endometrial cancer treated with lenvatinib plus pembrolizumab

.

Efficacy and safety of combination therapy with lenvatinib and pembrolizumab in elderly patients with advanced endometrial cancer

Background. Currently, women over 65 years of age comprise a quarter of endometrial cancer (EC) patients, but this population remains underrepresented in clinical trials. The combination therapy with lenvatinib plus pembrolizumab has demonstrated a significant improvement in progression-free survival and overall survival in patients with mismatch repair system proficiency (pMMR/MSS) after a single prior treatment line. However, data on the efficacy and safety of this regimen in real-world clinical practice, especially in elderly patients, are limited.Aim. To describe the efficacy and safety of EC therapy with lenvatinib and pembrolizumab in elderly patients.Materials and methods. In this retrospective single-center study conducted at a Moscow hospital (December 2020 – March 2024), we collected data on the efficacy and safety of lenvatinib and pembrolizumab therapy in 26 patients over 65 years of age. Patients with pathologically confirmed EC without evidence of microsatellite instability were included. The primary endpoint of the study was progression-free survival; additionally, we evaluated the clinical characteristics of the patients, analyzed the objective response rate and the incidence of adverse events.Results. The median age was 69 (65–81) years, 23 % of patients were older than 75 years. The performance status of 92.3 % of patients was classified as ECOG 0–1, endometrial adenocarcinoma was the most frequently detected type (61.5 % of cases), serous carcinoma was reported in 10 (38.5 %) patients. The median number of prior treatment lines was 3 (2–6). The objective response rate reached 25 %, and the disease control rate was 75 %. The median progression-free survival was 5.67 (1.4–35.3) months. Adverse events of any grade were noted in 24 (92.3 %) patients. Lenvatinib dose reduction was performed in 76.9 % of cases. The most frequent adverse events were arterial hypertension (in 16 (61.5 %) patients), fatigue (in 5 (19.2 %) patients), and diarrhea (in 3 (11.5 %) patients).Conclusion. In this real-world clinical practice study in Russia involving patients with recurrent and metastatic EC without mismatch repair system deficiency (pMMR/MSS) over 65 years of age who received lenvatinib plus pembrolizumab, the efficacy and safety of the treatment were comparable to those reported in earlier studies, suggesting the feasibility of combination therapy in this population with appropriate attention to performance status and management of adverse events. Additional studies are required to evaluate the efficacy and safety of the combination therapy of lenvatinib and pembrolizumab in patients with a more severe functional status.

Immunotherapy and PARP inhibitors as first-line treatment in endometrial cancer: A systematic review and network meta-analysis.

Immunotherapy and PARP inhibitors as first-line treatment in endometrial cancer: A systematic review and network meta-analysis.

A predictive model for endometrial cancer recurrence based on molecular markers and clinicopathologic parameters: A double-center retrospective study.

A predictive model for endometrial cancer recurrence based on molecular markers and clinicopathologic parameters: A double-center retrospective study.

Genetic predictors of unexpected recurrence in low-risk endometrial cancer: A comprehensive genomic analysis reveals FGFR2 as a risk factor and a rare fatal POLE-mutated recurrence.

Genetic predictors of unexpected recurrence in low-risk endometrial cancer: A comprehensive genomic analysis reveals FGFR2 as a risk factor and a rare fatal POLE-mutated recurrence.

Real-world outcomes in molecular subgroups for patients with advanced or recurrent endometrial cancer treated with platinum-based chemotherapy.

There is scarce real-world evidence on patients with advanced/recurrent endometrial cancer treated with platinum-based chemotherapy. We assessed the oncological outcome in groups by molecular classification. This retrospective cohort study included patients with advanced/recurrent endometrial cancer treated with platinum-based chemotherapy after hysterectomy at The Norwegian Radium Hospital, Oslo University Hospital, Norway, between January 2006 and December 2017. Patients were molecularly classified as pathogenic POLE mutated, mismatch repair deficient, p53 abnormal, or no specific molecular profile. Time-to-recurrence and cancer-specific survival were calculated. We identified 264 advanced-stage patients (stage III/IV) and 96 patients with recurrent disease. The molecular classification was prognostic for time-to-recurrence (p < .0001) and cancer-specific survival (p < .0001) in patients with advanced disease, but the outcome did not differ significantly by molecular groups in recurrent patients. In all molecular groups, patients with stage III disease had longer time-to-recurrence and cancer-specific survival compared to patients with stage IV disease. The worst outcome was observed in patients with p53 abnormal tumors with an HR of 1.57 (95% CI 1.07 to 2.30) for time-to-recurrence and HR of 1.78 (95% CI 1.19 to 2.65) for cancer-specific survival in stage III/IV disease and an HR of 1.45 (95% CI 0.83 to 2.52) for time-to-recurrence and HR of 1.60 (95% CI 0.99 to 2.68) for cancer-specific survival in patients with recurrent disease. The few patients with POLE mutated tumors had favorable outcomes despite the advanced/recurrent disease status. Oncological outcomes differ by molecular groups, in particular among patients with advanced disease. Patients with p53 abnormal tumors have the worst outcome, while patients with POLE mutated tumors have favorable outcomes even with recurrent disease. Implementation of the addition of immunotherapy to chemotherapy is expected to lead to substantial improvement of outcome, particularly in patients with mismatch repair deficient advanced/recurrent disease. There is still a high unmet need in advanced/recurrent patients with p53 abnormal and no specific molecular profile tumors.

Training, Validating, and Testing Machine Learning Prediction Models for Endometrial Cancer Recurrence.

Endometrial cancer (EC) is the most common gynecologic cancer in the United States with rising incidence and mortality. Despite optimal treatment, 15%-20% of all patients will recur. To better select patients for adjuvant therapy, it is important to accurately predict patients at risk for recurrence. Our objective was to train, validate, and test models of EC recurrence using lasso regression and other machine learning (ML) and deep learning (DL) analytics in a large, comprehensive data set. Data from patients with EC were downloaded from the Oncology Research Information Exchange Network database and stratified into low risk, The International Federation of Gynecology and Obstetrics (FIGO) grade 1 and 2, stage I (N = 329); high risk, or FIGO grade 3 or stages II, III, IV (N = 324); and nonendometrioid histology (N = 239) groups. Clinical, pathologic, genomic, and genetic data were used for the analysis. Genomic data included microRNA, long noncoding RNA, isoforms, and pseudogene expressions. Genetic variation included single-nucleotide variation (SNV) and copy-number variation (CNV). In the discovery phase, we selected variables informative for recurrence (P < .05), using univariate analyses of variance. Then, we trained, validated, and tested multivariate models using selected variables and lasso regression, MATLAB (ML), and TensorFlow (DL). Recurrence clinic models for low-risk, high-risk, and high-risk nonendometrioid histology had AUCs of 56%, 70%, and 65%, respectively. For training, we selected models with AUC >80%: five for the low-risk group, 20 models for the high-risk group, and 20 for the nonendometrioid group. The two best low-risk models included clinical data and CNVs. For the high-risk group, three of the five best-performing models included pseudogene expression. For the nonendometrioid group, pseudogene expression and SNV were overrepresented in the best models. Prediction models of EC recurrence built with ML and DL analytics had better performance than models with clinical and pathologic data alone. Prospective validation is required to determine clinical utility.

Integrative analysis of DNA methylation, RNA sequencing, and genomic variants in the cancer genome atlas (TCGA) to predict endometrial cancer recurrence.

The prognosis within each subtype varies due to histological and molecular factors. This study leverages omics datasets and machine learning to identify biomarkers associated with EC recurrence in different molecular subtypes. Utilizing DNA methylation, RNA-sequencing, and common variant data from 116 EC samples in The Cancer Genome Atlas (TCGA), differentially expressed genes (DEGs) and differentially methylated regions (DMRs) were identified using t-tests between recurrence and non-recurrence groups. These were visualized through volcano plots and heat maps, while decision trees and random forests classified and stratified the samples. A machine learning analysis combined with box plots showed that in the copy number-high (CN-H) recurrence group, PARD6G-AS1 had decreased methylation, CSMD1 had increased methylation, and TESC expression was higher than the non-recurrence group. In the copy number-low (CN-L) recurrence group, CD44 expression was elevated. Further validation using TCGA clinical data confirmed PARD6G-AS1 hypomethylation and CD44 overexpression as significant indicators of recurrence (p=0.006 and p=0.02, respectively), and both were linked to advanced stage and lymph node metastasis. The study concludes that PARD6G-AS1 hypomethylation and CD44 overexpression are potential predictors of recurrence in CN-H and CN-L EC patients, respectively.

Abstract 3839: MIG-6 plays as a tumor suppressor to inhibit angiogenesis by downregulating HDAC1 in PTEN-deficient endometrial cancer

Abstract Endometrioid endometrial cancer (EEC) is the most prevalent gynecological malignancy. Metastatic and recurrent endometrial cancer is incurable with currently available standard therapies. While Mig-6 mutation develops distant metastasis and recurrence of EEC with Pten deficiency, Mig-6 overexpression (Ptend/dMig-6over mice) suppresses tumor development. Therefore, there is an urgent need to explore the mechanisms of tumor metastasis and recurrence to further elucidate the progression of EEC. We performed RNA-seq analysis to identify targets of Mig-6 in Ptend/d and Ptend/dMig-6over mice. The transcriptomic analysis identified 104 and 518 genes significantly increased or decreased transcripts in Ptend/dMig-6over mice compared to Ptend/d mice. The pathway analysis of these dysregulated genes showed significant inhibition of immune, inflammatory, and angiogenesis pathways in Ptend/dMig-6over compared to the Ptend/d mice group, where the key regulator was hypoxia-inducible factor-1 (HIF1A). Immunohistochemical analysis of HIF1A and PECAM1 validated a significant reduction of angiogenesis in Ptend/dMig-6over mice. Moreover, combined interactome and immunoprecipitation analyses revealed that MIG-6 directly binds with histone deacetylase 1 (HDAC1) in the EEC of Ptend/dMig-6over mice. Our double immunofluorescence results confirmed colocalization of two proteins in EEC. Finally, we evaluated the therapeutic effect of Panobinostat, a HDAC inhibitor, in EEC of Ptend/d mice. Our results demonstrate the tumor suppressor role of MIG-6 as an HDAC1 interacting protein in angiogenesis of EEC. Our findings highlight potential molecular targets of EEC that could significantly enhance therapeutic strategies for endometrial cancer. Citation Format: Shamsun Nahar, Jiyoung Yu, Haeam Lee, Rong Li, Jin-Seok Jung, Tae Hoon Kim, Kyunggon Kim, Jung-Yoon Yoo, Jae-Wook Jeong. MIG-6 plays as a tumor suppressor to inhibit angiogenesis by downregulating HDAC1 in PTEN-deficient endometrial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3839.

Abstract 4020: Review of literature on the effect of stress and anxiety among African-American breast and endometrial cancer patients

Abstract African American women face disproportionately higher rates of breast and endometrial cancer recurrence compared to their Caucasian counterparts, highlighting an urgent need to explore the role of stress in cancer progression and recurrence. This study conducts a systematic review of the literature to evaluate the efficacy of stress and anxiety interventions in reducing cancer risk among African American survivors. By analyzing 25 articles from 2014-2024, this review examines the correlation between psychological stress, biological stress markers, and cancer outcomes. The findings emphasize the significant impact of stress on health outcomes, particularly in the context of cortisol's role in metabolism and immune response. The review also explores coping mechanisms, including social support, diet, and exercise, tailored to African American women's cultural and socioeconomic needs. The results underscore the critical need for targeted interventions to address stress in this population, with implications for improving cancer survivorship and advancing healthcare equity. Citation Format: Gabrielle Ford, Zakirah L. Abdul-Hameed, Amirah Burton, Brian M. Rivers, Desiree Rivers. Review of literature on the effect of stress and anxiety among African-American breast and endometrial cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4020.

Evaluation of early chemotherapy response by combining static- and dynamic [18F]FDG-PET with diffusion-weighted MRI in subcutaneous patient-derived endometrial cancer mouse models

BackgroundThe combination of carboplatin and paclitaxel is the standard chemotherapy for treatment of high-risk and recurrent endometrial cancer. Evaluation of treatment response by diagnostic imaging is routinely carried out months after start of treatment, and is based on changes in tumor size or appearance of new metastases. The aim of this study was to evaluate early chemotherapeutic response in two subcutaneous endometrial cancer mouse models generated from patient-derived organoids using static- and dynamic [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) and diffusion-weighted (DW) magnetic resonance imaging (MRI). Mice were injected bilaterally with endometrioid endometrial cancer grade 3 (EEC G3), International Federation of Gynaecology and Obstetrics (FIGO) stage 3C1 (Model A) or stage 1B (Model B) organoids (n = 15 mice). The mice were randomized into treatment (combined carboplatin and paclitaxel, nA=8 / nB=6 tumors) or control (saline, nA=8 / nB=8 tumors) groups. During tumor progression, the mice underwent T2-weighted (T2w) MRI, DW-MRI and dynamic [18F]FDG-PET at baseline/Day 0 (start of treatment), Day 3 (early) and Day 10 (endpoint) using a sequential PET-MRI small-animal scanner.ResultsAt endpoint, tumor volumes at T2w-MRI (vMRI) were lower in the treatment groups in both models (p ≤ 0.029). The tumor metabolic rate (MRFDG) from dynamic PET, was significantly lower in the treatment group at the early timepoint (Day 3) and at the endpoint in Model A (p ≤ 0.042). In Model B, MRFDG was similar for both groups at Day 3 and at endpoint (p≥0.217). The 10 tumor voxels with the highest standardised uptake value (SUV10) from static [18F]-FDG-PET was significantly lower at endpoint in the treatment groups in both models (p ≤ 0.041), but not at the early timepoint (p≥0.083). Similarly, the tumor apparent diffusion coefficient (ADCmean) was significantly higher indicating treatment response at endpoint for treatment groups in both models (p ≤ 0.036).ConclusionsMultimodal imaging is feasible for evaluation of early signs of treatment response in preclinical subcutaneous endometrial cancer models. The novel MRFDG dynamic PET imaging parameter seems most promising for detecting very early treatment response following chemotherapy.

A randomized phase II/III study of paclitaxel/carboplatin/metformin versus paclitaxel/carboplatin/placebo as initial therapy for measurable stage III or IVA, stage IVB, or recurrent endometrial cancer: An NRG oncology/GOG study.

A randomized phase II/III study of paclitaxel/carboplatin/metformin versus paclitaxel/carboplatin/placebo as initial therapy for measurable stage III or IVA, stage IVB, or recurrent endometrial cancer: An NRG oncology/GOG study.

Effect of substantial lymphovascular space invasion on location of first disease recurrence in surgical stage I endometrioid endometrial adenocarcinoma.

Lymphovascular invasion can predict nodal spread and recurrence in endometrioid endometrial cancer; however, the impact of lymphovascular invasion quantification on local versus distant recurrence in surgically staged patients has not yet been established. This multicenter, retrospective cohort study included surgically staged patients with International Federation of Obstetrics and Gynecology 2009 stage I node-negative endometrioid endometrial cancer. Patients were treated between January 2012 and December 2019 at 2 tertiary cancer centers. Staging included a total hysterectomy and lymph node assessment. The extent of lymphovascular invasion was defined using the World Health Organization criteria as focal (<5 vessels involved on at least 1 pathology slide) or substantial (≥5 vessels involved). Recurrence and death were considered as events. A competing risk analysis was performed and controlled for multicenter clustering. Overall, 1555 patients met the inclusion criteria: 65 (4.2%) had substantial invasion, 119 (7.7%) had focal, and 1371 (88.2%) had no invasion. The median follow-up was 61.5 months (range; 0.8-133.9). There were 173 evaluable events among the 1554 patients: 56 local recurrences, 43 distant recurrences, and 74 deaths without recurrence. Deep (>50%) myoinvasion and grade 3 histology were more frequently observed in patients with substantial myoinvasion. Overall, 323 patients (20.8%) received adjuvant therapy. The 5-year cumulative incidence failure rates for any recurrence were 6.0% for no, 19.5% for focal, and 19.0% for substantial invasion. Compared to no lymphovascular invasion, substantial invasion was associated with an increased risk of distant recurrence (adjusted HR 2.29, 95% CI 1.17 to 4.46). In patients with surgical stage I endometrioid endometrial cancer, the focal and substantial lymphovascular invasion was associated with a 3-fold increased risk of cumulative incidence failure versus no lymphovascular invasion. Patients with substantial invasion had more deeply invasive and grade 3 tumors and appeared to experience more distant than local recurrences. These findings challenge the International Federation of Obstetrics and Gynecology 2023 staging classification that combines no lymphovascular invasion and focal lymphovascular invasion into a single risk category.

Serial Circulating Tumor DNA Sequencing to Monitor Response and Define Acquired Resistance to Letrozole/Abemaciclib in Endometrial Cancer.

In a phase II study, letrozole/abemaciclib demonstrated an objective response rate of 30% and a median progression-free survival (PFS) of 9.1 months in recurrent estrogen receptor-positive endometrial cancer (EC). While tissue-based tumor profiling revealed several mechanistically relevant candidate baseline genomic predictors of response, circulating tumor DNA (ctDNA) is a less invasive alternative to monitor therapeutic efficacy and define acquired resistance. Serial plasma specimens were obtained at baseline, C2D1, C3D1, C8D1, the time of objective response, and the time of progression. Samples were analyzed using the Guardant Reveal assay to assess methylation-based tumor fraction (TF), with the Guardant360 assay providing genotyping of >700 genes in samples with detectable ctDNA. Treatment response was assessed using a measure of the relative change in TF pre- versus on-treatment. A total of 99 of 102 (97%) samples from 28 patients were successfully analyzed. Patients with above median baseline TF exhibited worse median PFS (2.0 months v 16.5 months, P < .005, hazard ratio [HR], 24.1) and worse overall survival (OS) (10.7 months v not yet reached, P < .005, HR, 14.8). Patients with molecular response (MR) after the first or second cycle of letrozole/abemaciclib therapy had significantly better median PFS and OS regardless of the cutoff used for definition of MR. ctDNA analysis of postprogression specimens identified several acquired genomic alterations associated with resistance to letrozole/abemaciclib therapy in more than half of the patients, including PI3K pathway, receptor tyrosine kinase (FGFR1,2 and ERBB2 alterations), cell cycle pathway (RB1 and CCNE1 alterations), and ESR1 and MAPK pathway alterations. Two of the three patients with mismatch repair-deficient ECs acquired ESR1 mutations at the time of progression. Baseline and on-treatment ctDNA dynamics may provide an early indication of benefit from letrozole/abemaciclib in EC. ctDNA at the time of progression may identify resistance alterations that may inform subsequent therapy.

Real-world treatment patterns and clinical outcomes in patients with advanced or recurrent endometrial cancer re-challenged with platinum-based chemotherapy in Europe.

Although platinum re-challenge is a treatment option for patients with advanced/recurrent endometrial cancer, real-world outcomes for these patients in Europe are not well-documented. Thus, this study aimed to evaluate real-world treatment patterns and outcomes for platinum re-challenge in patients with advanced/recurrent endometrial cancer. Endometrial Cancer Health Outcomes-Europe (ECHO-EU) is a multi-center, retrospective, medical record review conducted in France, Germany, Italy, Spain, and the United Kingdom, evaluating treatment patterns and outcomes. Patients with advanced/recurrent endometrial cancer treated with first-line systemic therapy and experiencing disease progression between July 2016 and June 2019 were eligible for inclusion in ECHO-EU. This analysis used data from a subset of patients, the platinum re-challenge cohort, who received platinum-based chemotherapy as second-line therapy after previous adjuvant/neoadjuvant and/or first-line platinum therapy. Kaplan-Meier analyses since initiation of second-line therapy estimated real-world progression-free survival and overall survival. Of the 475 ECHO-EU patients, 70 patients (15%) were platinum re-challenged and had a median age of 67 years (range; 44-81). The platinum-free interval (PFI) was <6 months for 27 patients (38.6%) and >6 months for 43 patients (61.4%). Complete or partial response to second-line therapy were achieved in 37.1% of patients, with similar overall response rates reported for patients with PFI <6 months (33.3%) and PFI ≥6 months (39.5%). The median (95% CI) overall survival from second-line therapy was 12 months (11-not estimable [NE]) overall and 14.1 (8.7-NE) and 12.0 (10.5-NE) months for patients with PFI <6 months and PFI >6 months, respectively. The median real-world progression-free survival from initiation of second-line therapy was 8.1 months (95% CI 7.6 to 10.0) overall and 7.6 (95% CI 5.3 to 19.8) and 8.5 (95% CI 7.9 to 12.0) months for patients with PFI <6 months and PFI ≥6 months, respectively. Patients with advanced/recurrent endometrial cancer who were re-challenged with a platinum-based therapy had similar outcomes, irrespective of their PFI, indicating that further research is needed to assess the value of PFI in endometrial cancer. The findings also suggest an unmet medical need and scope for novel treatments that may improve the overall survival for these patients.

Randomized study evaluating optimal dose, efficacy, and safety of E7386 plus lenvatinib versus treatment of physician's choice in advanced/recurrent endometrial carcinoma previously treated with platinum-based chemotherapy and immune checkpoint inhibitors.

Randomized controlled trial data for patients with endometrial cancer who experience disease progression after anti-programmed cell death [ligand] 1 (PD-[L]1) therapy are lacking. E7386, a novel small-molecule inhibitor, has been shown to enhance anti-angiogenesis when combined with lenvatinib. The escalation and expansion parts of Study 102 showed preliminary anti-tumor activity and manageable safety of E7386 plus lenvatinib in patients with advanced, un-resectable, or recurrent endometrial cancer previously treated with anti-PD-(L)1. This study aimed to determine the optimal dose of E7386 in combination with lenvatinib. E7386 plus lenvatinib will show a manageable safety profile and clinically meaningful anti-tumor activity in patients with advanced, un-resectable, or recurrent endometrial carcinoma previously treated with chemotherapy and anti-PD-(L)1 therapy. Study 102 is an open-label, global, phase 1b/2 trial. Patients with endometrial carcinoma will be randomized 1:1:1:1 to E7386 120 mg twice daily plus lenvatinib 14 mg once daily, E7386 60 mg twice daily plus lenvatinib 14 mg once daily, lenvatinib 24 mg once daily monotherapy, or treatment of physician's choice (doxorubicin 60 mg/m2 once every 3 weeks or paclitaxel 80 mg/m2 once weekly [3 weeks on/1 week off]). Eligible patients are aged ≥18 years with Eastern Cooperative Oncology Group performance status of 0 to 1 and must have advanced, un-resectable, or recurrent endometrial carcinoma that has progressed on/after prior platinum-based chemotherapy and PD-(L)1-directed therapy. Up to 3 previous lines of therapy are permitted. Individuals with prior treatment with lenvatinib or E7386 or known intolerance and/or known hypersensitivity to E7386, lenvatinib, doxorubicin, or paclitaxel, or any of their excipients, are not eligible to participate. The primary end points are safety and the objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 by investigator assessment at week 24. The study aims to include 120 patients across approximately 80 investigational sites in North America, Europe, and Asia-Pacific regions. Estimated Dates for Completing Accrual and Presenting Results: Enrollment is expected to take approximately 9 months, with presentation of results in 2026. The trial is registered at ClinicalTrials.gov, NCT04008797.

Advancements in Endometrial Cancer Research in 2024

Endometrial cancer is one of the most common gynaecological cancers in high-income countries and, for many years, has been associated with poor outcomes for patients with advanced-stage disease. The results from the Phase III studies, RUBY Part 1 with dostarlimab, NRG-GY018 with pembrolizumab, and DUO-E with durvalumab, in patients with advanced or recurrent endometrial cancer in 2023 were practice-changing. The addition of immunotherapy to carboplatin–paclitaxel chemotherapy, followed by immunotherapy maintenance, led to a marked improvement in progression-free survival (PFS), particularly in patients with mismatch repair deficient, microsatellite stability-high (dMMR/MSI-H) disease, and has transformed the treatment landscape for these patients. This article discusses the latest advancements in endometrial cancer research in 2024, including highlights from the Society for Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer 2024 in March, the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting in May and June, the European Society for Medical Oncology (ESMO) Congress 2024 in September, and the Annual Global Meeting of the International Gynecologic Cancer Society (IGCS) 2024 in October. The article highlights the pivotal research conducted in 2024 in the chemotherapy–immunotherapy space, including the statistically significant and clinically meaningful overall survival (OS) benefit with dostarlimab in the overall population in RUBY Part 1. The PFS benefit with pembrolizumab, regardless of mismatch repair (MMR) status, and the early OS data in NRG-GY018 are also discussed. Additional topics covered in this year-in-review article include the effect of adding a poly adenosine diphosphate ribose polymerase (PARP) inhibitor to chemotherapy–immunotherapy combinations in DUO-E and RUBY Part 2, the unmet need in patients with MMR proficient/microsatellite stable (pMMR/MSS) disease, and the potential importance of adding PARP inhibitor for the pMMR/MSS population. 2024 was a pivotal year in endometrial cancer research, building on the first-line data that emerged in 2023 from key studies including RUBY, NRG-GY018, and DUO-E, and firmly establishing chemotherapy–immunotherapy combinations as the new standard of care for patients with dMMR disease. Other important developments in the endometrial cancer space in 2024 include the data from LEAP-001, which further support the use of chemotherapy-free combination treatment in patients with pMMR advanced or recurrent endometrial cancer after progression on systemic adjuvant or neoadjuvant chemotherapy.

HSR25-176: Efficacy of Immunochemotherapy in Primary Advanced or Recurrent Endometrial Cancer: A Systematic Review and Meta-Analysis of Phase II/III Randomized Controlled Trials (RCTs).

HSR25-176: Efficacy of Immunochemotherapy in Primary Advanced or Recurrent Endometrial Cancer: A Systematic Review and Meta-Analysis of Phase II/III Randomized Controlled Trials (RCTs).

HSR25-150: Meta-Analysis of Randomized Controlled Trials (RCTs) to Evaluate the Incidence of Health-Related Quality of Life (HRQOL) Events in Patients with Primary Advanced or Recurrent Endometrial Cancer Treated With First-Line Immunochemotherapy.

HSR25-150: Meta-Analysis of Randomized Controlled Trials (RCTs) to Evaluate the Incidence of Health-Related Quality of Life (HRQOL) Events in Patients with Primary Advanced or Recurrent Endometrial Cancer Treated With First-Line Immunochemotherapy.

HSR25-175: Meta-Analysis of Randomized Controlled Trials (RCTs) to Evaluate the Incidence of Venous Thromboembolism (VTE) and Immune-Related Adverse Events (iRAEs) in Patients With Primary Advanced or Recurrent Endometrial Cancer Treated With Immunochemotherapy.

HSR25-175: Meta-Analysis of Randomized Controlled Trials (RCTs) to Evaluate the Incidence of Venous Thromboembolism (VTE) and Immune-Related Adverse Events (iRAEs) in Patients With Primary Advanced or Recurrent Endometrial Cancer Treated With Immunochemotherapy.