A comprehensive analysis of immunotherapy in advanced endometrial cancer (Review).
Ontology highlight
ABSTRACT:
SUBMITTER: Wang L
PROVIDER: S-EPMC10773226 | biostudies-literature | 2024 Feb
REPOSITORIES: biostudies-literature
Publications
A comprehensive analysis of immunotherapy in advanced endometrial cancer (Review).
Wang Liping L Liu Lin L Huo Da D Zhang Yixiang Y
Oncology letters 20231228 2
The morbidity and mortality rates of endometrial cancer (EC) are increasing yearly. Early-stage EC can be effectively treated through surgery or surgery combined with radiotherapy and chemotherapy. Advanced and recurrent EC is treated with chemotherapy and comprehensive treatment; however, the prognosis for patients at this disease stage is poor. Consequently, novel and effective treatment strategies are urgently required for these patients. Breakthrough progress has been made with the use of im ...[more]
Similar Datasets
Project description:ObjectivePembrolizumab and dostarlimab are immune checkpoint inhibitors that target programmed death receptor 1 (PD-1). Combination anti-PD-1 regimens have been shown to exhibit favorable survival benefits when treating advanced endometrial cancer (EC). Which treatment was preferable will need to be confirmed by a cost-effectiveness comparison between them.MethodsBased on patient and clinical parameters from RUBY and NRG-GY018 phase III randomized controlled trials, the Markov model with a 20-year time horizon was established to evaluate the cost-effectiveness of dostarlimab plus chemotherapy (DC), pembrolizumab plus chemotherapy (PC), and chemotherapy alone (C) treatment for patients with mismatch repair-proficient microsatellite-stable (pMMR-MSS) and mismatch repair-deficient microsatellite instability-high (dMMR-MSI-H) advanced EC from the American payers' perspective. The main results include total cost, life-years (LYs), quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER) at a $150,000/QALY of willingness-to-pay.ResultsIn the pMMR-MSS population, DC, PC, and C produced costs (QALYs) of $99,205 (3.02), $322,530 (3.25), and $421,923 (4.40), resulting in corresponding ICERs of $974,177/QALY (PC vs. C), $234,527/QALY (DC vs. C), $86,671/QALY (DC vs. PC), respectively; In the dMMR-MSI-H population, DC, PC, and C obtained costs (QALYs) of $120,177 (5.73), $691,399 (8.43), and $708,787 (11.26), yielding ICERs of $266,423/QALY (PC vs. C), $135,165/QALY (DC vs. C), $7,866/QALY (DC vs. PC), respectively.ConclusionIn the US, DC was a more cost-effective treatment than PC for patients with advanced EC irrespective of MMR status. However, compared to C, DC was associated with more cost-effectiveness in the dMMR-MSI-H population.
| S-EPMC11790985 | biostudies-literature
Project description:The treatment of advanced stage, metastatic or recurrent endometrial cancer remains a clinically difficult scenario. Although combination carboplatin and paclitaxel is an effective standard-of-care regimen, alternate strategies have shown promise, particularly in biomarker select populations. In an effort to improve oncologic outcomes, investigators are exploring novel immunotherapy combinations. In this review, we discuss the clinical rationale and design of current phase III immuno-oncology clinical trials in patients with advanced stage or recurrent endometrial cancer.
| S-EPMC7970168 | biostudies-literature
Project description:BackgroundWe sought to determine the prevalence of germline pathogenic variants (gPVs) in unselected patients with endometrial cancer (EC), define biallelic gPVs within tumors, and describe their associations with clinicopathologic features.MethodsGermline assessment of at least 76 cancer predisposition genes was performed in patients with EC undergoing clinical tumor-normal Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) sequencing from January 1, 2015, to June 30, 2021. In patients with gPVs, biallelic alterations in ECs were identified through analysis of loss of heterozygosity and somatic PVs. Clinicopathologic variables were compared using nonparametric tests.ResultsOf 1625 patients with EC, 216 (13%) had gPVs, and 15 patients had 2 gPVs. There were 231 gPVs in 35 genes (75 [32%] high penetrance; 39 [17%] moderate penetrance; and 117 [51%] low, recessive, or uncertain penetrance). Compared with those without gPVs, patients with gPVs were younger (P = .002), more often White (P = .009), and less obese (P = .025) and had differences in distribution of tumor histology (P = .017) and molecular subtype (P < .001). Among 231 gPVs, 74 (32%) exhibited biallelic inactivation within tumors. For high-penetrance gPVs, 63% (47 of 75) of ECs had biallelic alterations, primarily affecting mismatch repair (MMR) and homologous recombination related genes, including BRCA1,BRCA2, RAD51D, and PALB2. Biallelic inactivation varied across molecular subtypes with highest rates in microsatellite instability-high (MSI-H) or copy-number (CN)-high subtypes (3 of 12 [25%] POLE, 30 of 77 [39%] MSI-H, 27 of 60 [45%] CN-high, 9 of 57 [16%] CN-low; P < .001).ConclusionsOf unselected patients with EC, 13% had gPVs, with 63% of gPVs in high-penetrance genes (MMR and homologous recombination) exhibiting biallelic inactivation, potentially driving cancer development. This supports germline assessment in EC given implications for treatment and cancer prevention.
| S-EPMC10165491 | biostudies-literature
Project description:ObjectiveEndometrial cancer uncommonly presents at an advanced stage and little prospective evidence exists to guide the management thereof. We aimed to summarize the evidence about primary cytoreductive surgery in the treatment of advanced stage endometrial cancer.Data sourcesMEDLINE, Embase, and Scopus databases were searched from inception to September 11, 2020, using search terms representing the themes "endometrial cancer," "advanced stage," and "primary cytoreductive surgery."Study eligibility criteriaWe included full-text, English reports that included ≥10 patients undergoing primary cytoreductive surgery for advanced stage endometrial cancer and that reported on the outcomes of primary cytoreductive surgery and survival rates based on the residual disease burden.MethodsTwo reviewers independently screened the studies and with disagreements between the reviewers resolved by a third reviewer. Data were extracted using a standardized form. The percentage of cases reaching maximal (no gross residual disease) and optimal (<1 cm or <2 cm residual disease) cytoreduction were assessed by summing binomials proportions, and the association with survival was assessed using an inverse variance-weighted meta-analysis of logarithmic hazard ratios.ResultsFrom 1219 unique records identified, 34 studies were selected for inclusion. Studies consisted of single or multi-institutional cohorts of patients collected over a period of 6 to 24 years and included various mixes of histologies (endometrioid, serous, clear cell, and carcinosarcoma) and disease stages (III or IV). In a meta-analysis of the extent of residual disease after primary cytoreductive surgery, we found that 52.1% of cases reached no gross residual disease status (n=18 studies; 1329 patients) and 75% reached <1 cm residual disease status (n=27 studies; 2343 patients). The proportion of cytoreduction for both thresholds was lower for studies of stage IV vs stage III to IV disease (41.4% vs 69.8% for no gross residual disease; 63.2% vs 82.2% for <1 cm residual disease) but did not vary notably by histology. In a meta-analysis of the reported hazard ratios, submaximal (any gross residual disease vs no gross residual disease) and suboptimal (≥1 cm vs <1 cm) cytoreduction thresholds were associated with worse progression-free survival (submaximal hazard ratio, 2.16; 95% confidence interval, 1.45-3.21; I2=68%; suboptimal hazard ratio, 2.55; 95% confidence interval, 1.93-3.37; I2=63%) and overall survival rates (submaximal hazard ratio, 2.57; 95% confidence interval, 2.13-3.10; I2=1%; suboptimal hazard ratio, 2.62; 95% confidence interval, 2.20-3.11; I2=15%). Sensitivity analyses limited to high-quality studies demonstrated consistent results.ConclusionAmong cases of advanced stage endometrial cancer undergoing primary cytoreductive surgery, a significant proportion of patients are left with residual disease, which is associated with worse survival outcomes. Further investigations about the roles of neoadjuvant chemotherapy and primary cytoreductive surgery in prospective trials is warranted in this population.
| S-EPMC8717361 | biostudies-literature
Project description:ObjectiveWhile primary cytoreductive surgery (PCS) is considered the standard of care for women who present with stage IV endometrial cancer, neoadjuvant chemotherapy (NACT) followed by interval cytoreductive surgery (ICS) has emerged as an alternative treatment strategy. We summarized the literature and compared outcomes of PCS compared to NACT and ICS.MethodsWe conducted a systematic search on PubMed, Embase, Web of Science, and Scopus for articles published from January 1, 1990 to December 31, 2020. Key search terms included multiple descriptors of advanced disease status in combination with "endometrial cancer" and "neoadjuvant chemotherapy". Our review included studies that examined survival and surgical outcomes of patients with stage III or IV endometrial cancer treated with neoadjuvant chemotherapy followed by interval cytoreductive surgery versus those who received primary cytoreductive surgery. We excluded studies examining only patients with leiomyosarcomas, carcinosarcomas, and stromal sarcomas due to the biologic heterogeneity of these malignancies.ResultsThe nine included studies encompassed 5,844 patients, of which 1,317 (22.5%) received NACT and 4,527 received PCS (77.5%). With the exception of a single study, all were retrospective observational studies or case series. Use of NACT in patients with stage IV EC increased from 16.0% in 2010 to 23.9% in 2015. Five studies analyzed median overall survival and all but one reported no significant difference between NACT + ICS vs. PCS. Optimal cytoreduction (<1 cm of residual disease) rates were similar across both treatment groups in three separate analyses, however pooled data suggest improved rates of optimal cytoreduction for NACT + ICS vs. PCS patients (81.9% vs. 51.5% respectively). Patients receiving NACT experienced significantly shorter hospital admissions and lower operative times compared to PCS counterparts.ConclusionsNACT followed by ICS reduces perioperative morbidity while offering similar overall survival.
| S-EPMC8601999 | biostudies-literature
Project description:BackgroundEndometrial cancer (EC) is one of the most prevalent malignancies in the female population. Homeoboxes (HOXs) are a large family of transcription factors that have a variety of functions in biological processes (BPs), including developmental differentiation, and their dysregulated expression has been implicated in tumorigenesis. However, the involvement of HOXs in EC has received little attention. Thus, we aimed to identify the potential role of HOXs in EC from a multi-omics perspective through bioinformatics analysis.MethodsWe obtained transcriptome, mutation, and methylation data and the corresponding clinical data for normal and tumor tissues from The Cancer Genome Atlas (TCGA) database. Abnormal expression of HOXs in EC was identified via differential analysis, and the diagnostic value of HOXs in EC was assessed with the receiver operating characteristic (ROC) method. Univariate and multivariate Cox regression models were employed to evaluate the predictive efficacy of HOXs in EC. Methylation and mutation analyses revealed epigenetic and genetic sequence alterations in HOXs. Single-sample gene set enrichment analysis (ssGSEA) was used to explore the altered immune microenvironment in EC. Moreover, the gene activity and pathway enrichment of downstream key HOX genes were revealed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis in EC.ResultsHOXs were found to be linked to the growth of EC and potentially playing a role in establishing the tumor immune microenvironment in patients with EC. HOXB9 was found to be a vital prognostic molecule in patients with EC and is expected to contribute to a novel treatment approach.ConclusionsWe used bioinformatics techniques to clarify the potential role of HOXs from a multi-omics perspective, and our findings provide a foundation for future investigations into the molecular mechanisms of HOXs in EC.
| S-EPMC10774039 | biostudies-literature
Project description:BackgroundPHGDH (Phosphoglycerate Dehydrogenase) is the first branch enzyme in the serine biosynthetic pathway and plays a vital role in several cancers. However, little is known about the clinical significance of PHGDH in endometrial cancer.MethodsClinicopathological data of endometrial cancer were downloaded from the Cancer Genome Atlas database (TCGA). First, the expression of PHGDH in pan-cancer was investigated, as well as the expression and prognostic value of PHGDH in endometrial cancer. The effect of PHGDH expression on the prognosis of endometrial cancer was analyzed by Kaplan-Meier plotter and Cox regression. The relationship between PHGDH expression and clinical characteristics of endometrial cancer was investigated by logistic regression. Receiver operating characteristic (ROC) curves and nomograms were developed. Possible cellular mechanisms were explored using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, the Gene Ontology (GO), and gene set enrichment analysis (GSEA). Finally, TIMER and CIBERSORT were used to analyze the relationship between PHGDH expression and immune infiltration. CellMiner™ was used to analyze the drug sensitivity of PHGDH.ResultsThe results showed that PHGDH expression was significantly higher in endometrial cancer tissues than in normal tissues at mRNA and protein levels. Kaplan-Meier survival curves showed that patients in the high expression group had shorter overall survival (OS) and disease free survival (DFS) than patients in the low PHGDH expression group. Multifactorial COX regression analysis further supported that high PHGDH expression was an independent risk factor associated with prognosis in patients with endometrial cancer. The results showed estrogen response, mTOR, K-RAS, and epithelial mesenchymal transition (EMT) were differentially elevated in the high-expression group of the PHGDH group. CIBERSORT analysis showed that PHGDH expression is related to the infiltration of multiple immune cells. When PHGDH is highly expressed, the number of CD8+T cells decreases.ConclusionPHGDH plays a vital role in the development of endometrial cancer, which is related to tumor immune infiltration, and can be used as an independent diagnostic and prognostic marker for endometrial cancer.
| S-EPMC9942409 | biostudies-literature
Project description:Immune checkpoint inhibitors (ICIs) targeting the programmed cell death (PD)-1 protein and its ligand, PD-L1, and cytotoxic T-lymphocyte-associated antigen (CTLA)-4, have revolutionized the management of patients with advanced non-small cell lung cancer (NSCLC). Unfortunately, only a small portion of NSCLC patients respond to these agents. Furthermore, although immunotherapy is usually well tolerated, some patients experience severe immune-related adverse events (irAEs). Liquid biopsy is a non-invasive diagnostic procedure involving the isolation of circulating biomarkers, such as circulating tumor cells (CTC), cell-free DNA (cfDNA), and microRNAs (miRNAs). Thanks to recent advances in technologies, such as next-generation sequencing (NGS) and digital polymerase chain reaction (dPCR), liquid biopsy has become a useful tool to provide baseline information on the tumor, and to monitor response to treatments. This review highlights the potential role of liquid biomarkers in the selection of NSCLC patients who could respond to immunotherapy, and in the identification of patients who are most likely to experience irAEs, in order to guide improvements in care.
| S-EPMC8070633 | biostudies-literature
Project description:BackgroundEndometrial cancer (EC) represents the sixth most common female tumor. In the advanced setting, the prognosis is dismal with limited treatment options. Platinum-based chemotherapy represents the actual standard of care in first-line chemotherapy, but no standard second-line chemotherapy is approved, with less than 1/4 of patients responding to second-line chemotherapy. In the last 10 years, immune checkpoint inhibitors (ICIs) have changed the treatment landscape of many solid tumors.MethodsThe review was conducted according to the PRISMA guidelines. We searched EMBASE, MEDLINE, Cochrane Database, and conference abstracts from international societies, up to November 2021. Clinical trials employing ICIs in advanced EC, written in English, were included. Reviews, letters, and commentaries were excluded. The overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety (number and grade of treatment-related adverse events [TRAEs]) were evaluated.Results15 studies, for a total of 1,627 patients, were included: 14 non-randomized phase I/II trials and 1 randomized phase III trial. Anti-PD1 (pembrolizumab, nivolumab, dostarlimab) and anti-PD-L1 agents (avelumab, atezolizumab, durvalumab) were administered as single agents; pembrolizumab and nivolumab were combined with the tyrosine-kinase inhibitors (TKI) lenvatinib and cabozantinib, respectively; and durvalumab was associated with anti-CTLA4 tremelimumab. 4 studies selected only MSI patients. Single agents determined an ORR from 26.7% to 58% among MSI patients, from 3% to 26.7% among MSS patients. DCR ranged from 53.5% to 88.9% in MSI, 31.4% to 35.2% in MSS patients. The combination of TKI and ICIs determined 32% to 63.6% of ORR in all-comers, 32%-36.2% in MSS patients. 54.2% to 76% of patients developed TRAEs. The combination of ICIs and TKI achieved a higher toxicity rate than single agents (≥G3 TRAEs 88.9%).ConclusionICIs represent an effective option for pretreated advanced EC patients with a tolerable profile. Given the encouraging results in MSI patients, every woman diagnosed with EC should be investigated for MS status. In MSS women, the combination of ICIs and TKI is more effective than monotherapy, notwithstanding safety concerns. PD-L1 cannot predict ICI response, whereas other biomarkers such as MSI and tumor mutational burden seem more accurate. Ongoing randomized trials will further clarify the role of these therapeutic options.Systematic review registrationPROSPERO, CRD42021293538.
| S-EPMC9047829 | biostudies-literature
Project description:BackgroundEndometrial cancer is one of the most common gynecological cancer in the world. However, the available adjuvant therapies, chemotherapy (CT) and radiotherapy (RT), demonstrated several limitations when used alone. Therefore, we conducted a meta-analysis to investigate the clinical effectiveness of chemoradiotherapy (CRT) based on overall survival (OS) and disease-free survival (DFS).MethodsA literature search was performed on five databases and one clinical trial registry to obtain all relevant articles. Search for studies was completed on September 9, 2021. A meta-analysis was conducted to determine the overall hazard ratio with the 95% Confidence Interval.ResultsA total of 17 articles with 23,975 patients in the CRT vs RT group and 50,502 patients in the CRT vs CT group were included. The OS Hazard Ratios (HR) of CRT compared to RT was 0.66 (95% CI [0.59-0.75]; P < 0.00001). Compared to CT, the OS HR was 0.70 (95% CI [0.64-0.78]; P < 0.00001). CRT also significantly improved the DFS compared to CT only (HR 0.79, 95% CI [0.64-0.97]; P = 0.02) However, CRT did not improve the DFS compared to RT only, with HR of 0.71 (95% CI [0.46-1.09]; P = 0.12).ConclusionAdjuvant CRT can significantly improve OS compared to CT or RT alone and improve the DFS compared to CT alone in patients with advanced endometrial cancer. Further research is needed to identify the optimal CRT regimen, and to whom CRT will be most beneficial.
| S-EPMC9695495 | biostudies-literature