Recurrent Endometrial Cancer Research Articles

Fertility-sparing treatment outcomes using immune checkpoint inhibitors in endometrial cancer patients with Lynch syndrome.

To evaluate the efficacy of immune checkpoint inhibitors (ICIs) for fertility-sparing treatment in Lynch syndrome-associated endometrial cancer (LS-EC). Four LS-EC cases received programmed cell death protein 1 (PD-1) inhibitors for fertility preservation at the Obstetrics and Gynecology Hospital of Fudan University from 2017 to 2023. The clinical data and long-term outcomes were retrospectively reviewed. Case 1, carrying germline MLH1 mutation, was diagnosed with Stage IIAmMMRd (International Federation of Gynecology and Obstetrics 2023) endometrial cancer (EC) at 38 years old. She received PD-1 inhibitor treatment and achieved a pathological complete response (CR) at 42 weeks. Case 2, carrying MLH1 mutation, underwent colorectal cancer surgery at 22 years and was diagnosed with EC and synchronous ovarian cancer at 39 years. After 24-week PD-1 treatment, CR of EC and ovarian cancer was achieved. Case 3, carrying MSH2 mutation, was diagnosed with endometrial atypical hyperplasia (EAH) at 35 years. After receiving 7-month progestin, she had the progressed disease with Stage IA2mMMRd EC and colon cancer was found soon after. She received PD-1 treatment for 18 weeks and achieved a CR of EC. She conceived naturally with full term delivery. Case 4, carrying MSH2 mutation, had a recurrence of Stage IBmMMRd EC 15 months after CR from EAH treated with progestin at 40 years. She received PD-1 treatment for 18 weeks and achieved CR. No recurrence was found in all cases after 3-41 months of follow-up after CR. ICIs might be an effective choice for LS-EC patients desiring fertility preservation.

Salvage interstitial brachytherapy for treatment of recurrent endometrial cancers in the vagina: Seven-year single institution experience and review of second recurrence patterns

Salvage interstitial brachytherapy for treatment of recurrent endometrial cancers in the vagina: Seven-year single institution experience and review of second recurrence patterns

Laparoscopic discoid rectal resection as surgical treatment of endometrial cancer recurrence

Laparoscopic discoid rectal resection as surgical treatment of endometrial cancer recurrence

Mismatch repair, p53, and L1 cell adhesion molecule status influence the response to chemotherapy in advanced and recurrent endometrial cancer

ObjectiveThis study aimed to identify the recurrence and survival rates according to the mismatch repair (MMR), p53, and L1 cell adhesion molecule (L1CAM) status in patients with advanced and recurrent endometrial cancer (EC) receiving systemic chemotherapy.MethodsThis single-center retrospective cohort study included chemotherapy-naïve patients with advanced-stage (III/IV) or recurrent EC between January 2015 and June 2022 (n = 156), who were administered chemotherapy as adjuvant therapy or first-line palliative treatment. MMR and p53 status were assessed, and L1CAM was tested using immunohistochemistry in the p53-wild and MMR-proficient (p53wt/pMMR) group. The primary outcomes were progression-free survival (PFS) and overall survival (OS).ResultsOf the 156 patients, 62 (39.7%), 53 (34.0%), and 41 (26.3%) had p53wt/pMMR, abnormal p53 (p53abn), and MMR-deficient (dMMR) tumors, respectively. PFS and OS were longest in dMMR, followed by p53wt/pMMR, and were the least in p53abn tumors (PFS: p = 0.0006, OS: p = 0.0013). After p53wt/pMMR was classified according to positive or negative L1CAM status, the L1CAM negative group exhibited significantly shorter survival rates than the L1CAM positive group (PFS: p = 0.0001, OS: p = 0.0027). p53abn tumors were independent prognostic factors for poor PFS (PFS: p = 0.039 on multivariable analysis).ConclusionIn chemotherapy-naïve patients with advanced and recurrent EC, there was a better prognosis in the order of MMR-D, p53wt/pMMR, and p53abn tumors after chemotherapy. L1CAM status is useful as a new marker to stratify p53wt/pMMR in advanced and recurrent groups.

A novel prognostic score of recurrence for endometrial cancer patients with staging surgery

BackgroundRecently, there have been an increasing number of reports on the association between inflammatory markers and the prognosis of malignant tumors. However, the current inflammatory indicators have limited accuracy. We aimed to develop a new scoring system for predicting endometrial cancer recurrence using inflammatory markers, tumor markers, and histological diagnoses.MethodsPatients with primary, previously untreated, and suspected endometrial cancer who underwent surgery at the Nara Medical University Hospital between January 2007 and December 2020 were included and followed up until March 2024. Items were divided into positive and negative using scores based on cutoff values and placed into the new scoring system, the endometrial tumor-related (ETR) score.ResultsWe found that positive postoperative histological examination of lymph node metastasis and myometrial invasion, high levels of carcinoembryonic antigen and D-dimer in preoperative blood tests, and a large difference in preoperative and postoperative white blood cell counts were significantly associated with recurrence. The sensitivity and specificity of recurrence prediction using the ETR score were not inferior to those using the International Federation of Gynecology and Obstetrics staging system, which is considered the best prognostic factor for survival.ConclusionsThe ETR score is a significant prognostic marker of recurrence in patients who have undergone staging surgery, with complete surgical tumor removal.

Surgical treatment of recurrent endometrial cancer with a pelvic abscess: a clinical case

The article presents a clinical case of a patient with stage IA endometrial cancer, who, at a later date following specialized treatment conducted according to established standards, was diagnosed with disease progression complicated by an abscess in the pelvic area. The treatment strategy involved radical surgical intervention, which included pelvic sanitation, abscess resolution, and simultaneous complete cytoreduction – resection of the sigmoid colon, ureteral ligation, creation of a single-barrel colostomy, and extended pelvic lymphadenectomy. A key factor in implementing the treatment plan was an interdisciplinary approach involving specialists from various fields to address both the oncological process and the resulting complications, which led to the effectiveness of the procedures performed.

Efficacy and safety of lenvatinib plus pembrolizumab in patients with endometrial cancer: data from an extended study of routine clinical practice in Russia

Aim. To assess the efficacy and safety of lenvatinib plus pembrolizumab for the treatment of mismatch repair-proficient (pMMR) endometrial cancer (EC) in routine clinical practice in Russia.Materials and methods. This multicenter, retrospective, cohort study included 114 patients with recurrent and metastatic EC from 37 cancer centers in Russia treated between December 2020 and November 2024. Patients with histologically verified EC without microsatellite instability were included. The primary endpoint was progression-free survival; the clinical characteristics of the patients were additionally analyzed; the objective response rate and the toxicity profile of therapy were assessed.Results. Median patients’ age was 66.5 (33–83) years. The most common histologic tumor subtype was endometrioid adenocarcinoma (72.8 %); serous adenocarcinoma was diagnosed in 18.4 % of cases, other subtypes – in 8.8 %. The median progression-free survival was 8.15 months (95 % confidence interval 0.4–41.1). Objective response rate was 38.0 %. The median overall survival was not achieved with a median follow-up of 12.23 months. During treatment, dose reduction rate due to adverse events was 50 %. The most frequent adverse events were hypertension (n = 64; 56.1 %), fatigue (n = 45; 39.5 %), and diarrhea (n = 20; 17.5 %).Conclusion. In the conducted study of routine clinical practice in Russian patients with recurrent and metastatic EC without mismatch repair system deficiency (pMMR/MSS), lenvatinib plus pembrolizumab showed good efficacy with a manageable safety profile.

Extended Survival and Prognostic Factors in Endometrial Cancer: A Multivariate Cox Regression Analysis

Background: Endometrial cancer (EC) is the third most prevalent neoplasm among women in Spain and the most frequent malignancy of the female genital tract. The primary risk factors are associated with increased estrogen levels. The objective of our study is to determine the current specific progression-free survival (PFS) and overall survival (OS) in patients with EC at the University Hospital of Puerto Real. Additionally, we aim to understand the independent role of specific factors in the risk of recurrence and mortality from EC through a multivariate analysis. Methods: A retrospective observational survival analysis of a case series was conducted. The study population included all women diagnosed and treated for EC in Spain between January 2010 and December 2021. The Kaplan-Meier method and Cox regression analysis were performed to evaluate survival based on patient age, tumor stage, histological type, and degree of differentiation, and to quantify survival probabilities for each factor. Results: A total of 324 patients were included. The PFS was 86.6% at 5 years and 81.1% at 10 years. The OS was 91.3% at 5 years and 84.8% at 10 years. The tumor-related mortality rate was 9.3% (N = 30) and the tumor recurrence rate was 5.6% (N = 18). The estimated median follow-up using the inverse Kaplan-Meier method was 4.33 years (95% confidence interval (95% CI): 3.72–4.94) for OS and 4.57 years (95% CI: 4.05–5.09) for PFS. The statistically significant factors affecting PFS and OS were age ≥60 years at diagnosis, advanced International Federation of Gynecology and Obstetrics (FIGO) stage (II–IV), non-endometrioid tumor, high tumor grade, and lymphovascular space invasion. Multivariate Cox regression analysis shows that being 60 years or older at the time of diagnosis, advanced FIGO stages, high tumor grade, and serous-papillary tumors are independent risk factors for recurrence or death in EC. Conclusions: Our study shows that being 60 years or older at the time of diagnosis, advanced FIGO stages (II–IV), non-endometrioid EC, higher histological tumor grade, and lymphovascular space invasion are associated with lower OS and PFS. Additionally, multivariate Cox analysis suggests that age ≥60 years at diagnosis, advanced FIGO stages, high tumor grade, and serous-papillary histological type are independent prognostic factors influencing survival and recurrence in EC. This study should serve as a foundation for further research, incorporating relevant aspects of the molecular biology of EC to refine patient prognosis.

A Phase II Study of Fulvestrant plus Abemaciclib in Hormone Receptor-Positive Advanced or Recurrent Endometrial Cancer.

Inhibition of the cyclin D-cyclin dependent kinase (CDK)4/6-INK4-retinoblastoma pathway can overcome acquired or de novo treatment resistance to endocrine monotherapy. Responses to endocrine monotherapy in advanced endometrial cancer (EC) are suboptimal, perhaps due to genomic alterations that promote estrogen receptor (ER)-independent cyclin D1-CDK4/6 activation. We hypothesized that addition of abemaciclib, a CDK4/6 kinase inhibitor, to antiestrogen therapy with fulvestrant will be an effective therapeutic strategy in patients with advanced or recurrent EC. In this phase II study, patients with advanced or recurrent EC received 150 mg of abemaciclib orally twice daily with 500 mg of fulvestrant intramuscularly monthly with a 2-week loading dose. Eligibility included ER or progesterone receptor expression ³1% by immunohistochemistry, measurable disease, £2 prior lines of chemotherapy, and £1 prior line of hormonal therapy. The primary endpoint was objective response rate (ORR) by RECIST v1.1. Twenty-seven patients initiated therapy and 25 were evaluable for efficacy. Eleven patients achieved partial response; 10 responses (91%) were in copy number-low/no specific molecular profile tumors, 1 (9%) was in a microsatellite instability-high tumor, and no responses were observed in copy number-high/TP53abnormal tumors. The ORR was 44% (90% CI, 27.0%-62.1%). Median duration of response was 15.6 months. Median progression-free survival was 9.0 months (90% CI: 1.8-20.4). The most common grade ³3 treatment-related adverse events were neutropenia (26%) and anemia (19%); no new safety signals were identified. The combination of abemaciclib and fulvestrant has promising activity with durable responses in advanced or recurrent EC; a randomized trial is planned.

The efficacy and safety of lenvatinib plus pembrolizumab in vulnerable patients with metastatic or recurrent endometrial cancer: a single institution experience.

Effective management with second-line therapy with the lenvatinib + pembrolizumab regimen for patients with advanced endometrial cancer is necessary. This retrospective study enrolled patients with endometrial cancer treated with the lenvatinib + pembrolizumab regimen. We evaluated progression-free survival (PFS), overall survival (OS), safety for patients non-eligible for the KEYNOTE775 trial, aged ≥65years, or with ECOG performance status 1-2. Forty-five patients were analyzed: 21 (47%) were aged ˃ 65years, 16 (36%) had performance status 1-2, and 15 (33%) were non-eligible for KEYNOTE775 trial participation. Overall, the median PFS was 8.5months (95% confidence interval [CI] 4.6-12.4), and the median OS was 15.6months (95% CI 9.4-NA). Median PFS was significantly shorter in patients not eligible for KEYNOTE775 participation and with performance status 1-2. The median OS was significantly shorter in patients with performance status 1-2. Grade ˃3 adverse events (AEs) occurred in 78% of patients who received the lenvatinib + pembrolizumab regimen. AEs resulted in lenvatinib dose reductions in 35 patients (78%) and lenvatinib and pembrolizumab discontinuation in 3 (7%) and 5 (11%), respectively. The median time to the first lenvatinib dose reduction was 1.5 (0.92-2.3) months in all patients and was significantly shorter in patients aged >65years. The current regimen has favorable efficacy and manageable safety with appropriate dose reduction of lenvatinib in the real world. However, the efficacy may be inferior in patients with performance status 1 or 2, heavily treated patients, and those with organ dysfunction. The current treatment status should reflect real-world data relative to the medical environment and management.

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

The purpose of this study was to establish a predictive model for endometrial cancer (EC) recurrence based on commonly used molecular markers and clinicopathologic parameters. This was a double-center retrospective study. The data of patients were retrospectively collected from two tertiary hospitals in Chongqing, China. The patients were divided into training and validation cohorts according to the ratio of 7:3. In the training cohort, the factors related to the recurrence were screened through uni- and multivariate Cox regression analysis, and a nomogram was constructed based on this. Internal and external validation of the model was performed in two cohorts, respectively. In the training cohort, the optimal risk threshold of the model was determined by using the receiver operating characteristic (ROC) curve and the maximum value of the Youden index. A total of 1348 patients were included, including 944 in the training cohort and 404 in the validation cohort. Multivariate analysis suggested that ER expression, P53 expression and other clinicopathologic parameters, were significantly related to recurrence. On this basis, a nomogram was constructed to predict 1-, 3-, and 5-year recurrence-free survival (RFS) rate. The model had good predictive accuracy in both cohorts through the validation. The ROC curve and Youden index suggested that the optimal risk threshold of 3-year RFS rate predicted by the model was 0.83, and there was a significant survival difference between the high- and low-risk groups. Compared to traditional prediction models, the model proposed in this study that combined molecular indicators and clinicopathologic parameters can better predict the prognosis of EC patients.

HTA12 The Cost-Effectiveness of Immunotherapies for Advanced or Recurrent Endometrial Cancer: A Systematic Review

HTA12 The Cost-Effectiveness of Immunotherapies for Advanced or Recurrent Endometrial Cancer: A Systematic Review

Nomogram Based on Immune-Inflammatory Score and Classical Clinicopathological Parameters for Predicting the Recurrence of Endometrial Carcinoma: A Large, Multi-Center Retrospective Study.

Surgery is the best approach to treat endometrial cancer (EC); however, there is currently a deficiency in effective scoring systems for predicting EC recurrence post-surgical resection. This study aims to develop a clinicopathological-inflammatory parameters-based nomogram to accurately predict the postoperative recurrence-free survival (RFS) rate of EC patients. A training set containing 1068 patients and an independent validation set consisting of 537 patients were employed in this retrospective study. The prognostic factors for RFS were identified by univariable and multivariable Cox proportional hazards regression analyses, and integrated into nomogram. The C-index, area under the curves (AUC), and calibration curves were employed to determine the predictive discriminability and accuracy of nomogram. Utilizing the nomogram, patients were stratified into low- and high-risk groups, and the Kaplan-Meier survival curve was further employed to assess the clinical efficacy of the model. Cox regression analyses revealed that age (HR = 1.769, P = 0.002), FIGO staging (HR = 1.790, P = 0.018), LVSI (HR = 1.654, P = 0.017), Ca125 (HR = 1.532, P = 0.023), myometrial invasion (HR = 1.865, P = 0.001), cervical stromal invasion (HR = 1.655, P = 0.033), histology (HR = 2.637, P < 0.001), p53 expression (HR = 1.706, P = 0.002), PLR (HR = 1.971, P = 0.003), SIRI (HR = 2.187, P = 0.003), and adjuvant treatment (HR = 0.521, P = 0.003) were independent prognostic factors for RFS in patients with EC. A combined clinicopathologic-inflammatory parameters model was constructed, which outperformed the single-indicator model and other established models in predicting the 1-, 3-, and 5-year RFS rates in patients with EC. The nomogram demonstrated sufficient accuracy in predicting the RFS probabilities of EC, enabling personalized clinical decision-making for future clinical endeavors.

Murine Xenograft Models as Preclinical Tools in Endometrial Cancer Research.

Murine xenograft models are valuable and increasingly used preclinical tools in cancer research to understand disease pathogenesis and guide treatment options. The aim of this narrative review is to summarize the studies that employed mouse xenograft models, using cell lines, patient-derived tumors, or organoids, in endometrial cancer (EC) research, detailing their methodology and main findings. We identified 27 articles reporting on heterotopic EC xenografts, including subcutaneous, subrenal capsule, intraperitoneal, and retro-orbital models, and 18 articles using orthotopic xenografts. Subcutaneous xenografts generated using either cell lines or patient tumors have been widely used; however, their low engraftment rates and the inability to recapitulate main clinical features such as metastases limit their translational value. Subrenal capsule models showed improved engraftment rates compared to subcutaneous models, but tumors exhibited slower and constrained tumor growth. Orthotopic models are technically more challenging to generate and monitor, but tumor growth occurs in a relevant microenvironment and EC ortho-xenografts exhibit high engraftment rates and metastases to clinically relevant sites. Cell line-based xenograft (CDX) models are attractive tools because they are convenient, easy to use, and amenable to genetic modifications, making them suitable for proof-of-concept approaches and large-scale studies. EC xenografts developed from patient tumors (PDTXs) are more labor/cost-intensive for their establishment but can capture the genetic and molecular heterogeneity within and across histologic subtypes and can inform personalized patient treatment. EC organoid-based xenograft (PDOX) models combine the advantages of both CDXs and PDTXs since they are more time- and cost-effective, faithfully maintain tumor characteristics and therapeutic responses, and can be genetically modified. Despite substantial progress in EC management, there are still several unmet needs. Efficient targeted treatments are currently indicated only for a small subgroup of patients, while women with recurrent or advanced-stage EC have very few therapeutic options and their prognosis remains unfavorable. Novel (targeted) drugs, combinational regimens and tools to predict the real drug response in patients are urgently needed. Xenograft models are expected to inform about disease mechanisms and to help identify novel therapeutic options and suitable target patients.

Epidemiology, Real-World Treatment Patterns, and Patient Outcomes of Primary Advanced or Recurrent Endometrial Cancer in Germany between 2015 and 2021

Introduction: The aim of this study was to describe the epidemiology of primary advanced or recurrent endometrial cancer and the outcomes from real-world treatment patterns of patients affected in Germany between 2015 and 2021. Methods: In this retrospective cohort study covering the period from 1 January 2015 to 31 December 2021, data from patients with primary advanced or recurrent endometrial cancer who initiated systemic treatment for their disease were extracted from an anonymized claims dataset from a regional health insurance fund in the German states of Saxony and Thuringia. Epidemiologic outcomes were cumulative incidence of endometrial cancer and point prevalence. Overall survival after the index date was assessed, with all-cause death used as an event. Endometrial cancer-related real-world treatment patterns were described for the post-index period. Results: The incidence of primary advanced or recurrent endometrial cancer in 2021 was 4.77 cases/100,000 persons, with no substantial change over time (4.63 in 2018; 4.93 in 2019; 4.45 in 2020). The point prevalence on 1 January 2022 was 0.023%, with a slight increase in prevalence observed from 1 January 2019 onwards. Among 466 patients with confirmed endometrial cancer, the mean (standard deviation) age was 68.0 (11.6) years; the tumor material from 86 patients (18.5%) underwent immunohistochemistry or polymerase chain reaction testing. Median overall survival was estimated to be 47.5 months (95% CI: 35.1–70.4) and the 5-year survival probability was 46.2%. The most frequent first-line systemic therapies were carboplatin (45.7%) and paclitaxel (43.1%). Second-line therapy was received by 153 patients (32.8%). Conclusion: The analysis of the German claims data produced contemporary epidemiologic estimates for advanced or recurrent endometrial cancer. Treatments were aligned with guideline recommendations during the study period, with tumor testing yet to enter mainstream practice. Introduction: The aim of this study was to describe the epidemiology of primary advanced or recurrent endometrial cancer and the outcomes from real-world treatment patterns of patients affected in Germany between 2015 and 2021. Methods: In this retrospective cohort study covering the period from 1 January 2015 to 31 December 2021, data from patients with primary advanced or recurrent endometrial cancer who initiated systemic treatment for their disease were extracted from an anonymized claims dataset from a regional health insurance fund in the German states of Saxony and Thuringia. Epidemiologic outcomes were cumulative incidence of endometrial cancer and point prevalence. Overall survival after the index date was assessed, with all-cause death used as an event. Endometrial cancer-related real-world treatment patterns were described for the post-index period. Results: The incidence of primary advanced or recurrent endometrial cancer in 2021 was 4.77 cases/100,000 persons, with no substantial change over time (4.63 in 2018; 4.93 in 2019; 4.45 in 2020). The point prevalence on 1 January 2022 was 0.023%, with a slight increase in prevalence observed from 1 January 2019 onwards. Among 466 patients with confirmed endometrial cancer, the mean (standard deviation) age was 68.0 (11.6) years; the tumor material from 86 patients (18.5%) underwent immunohistochemistry or polymerase chain reaction testing. Median overall survival was estimated to be 47.5 months (95% CI: 35.1–70.4) and the 5-year survival probability was 46.2%. The most frequent first-line systemic therapies were carboplatin (45.7%) and paclitaxel (43.1%). Second-line therapy was received by 153 patients (32.8%). Conclusion: The analysis of the German claims data produced contemporary epidemiologic estimates for advanced or recurrent endometrial cancer. Treatments were aligned with guideline recommendations during the study period, with tumor testing yet to enter mainstream practice.

A nomogram model to predict recurrence of early-onset endometrial cancer after resection based on clinical parameters and immunohistochemical markers: a multi-institutional study.

This study aimed to investigate the prognosis value of the clinical parameters and immunohistochemical markers of patients with early-onset endometrial cancer (EC) and establish a nomogram to accurately predict recurrence-free survival (RFS) of early-onset EC after resection. A training dataset containing 458 patients and an independent testing dataset consisting of 170 patients were employed in this retrospective study. The independent risk factors related to RFS were confirmed using Cox regression models. A nomogram model was established to predict RFS at 3 and 5 years post-hysterectomy. The C-index, area under the curve (AUC) of the receiver operating characteristic (ROC) curve, and calibration curve were calculated to assess the predictive accuracy of the nomogram. In all early-onset EC patients, more than half (368/628, 58.6%) were diagnosed in the age range of 45-49 years. Meanwhile, the recurrence rate of early-onset EC is approximately 10.8%. Multivariate Cox regression analyses showed that histological subtype, FIGO stage, myometrial invasion, lymphovascular space invasion (LVSI), P53 expression, and MMR status were independent prognostic factors related to RFS (all P < 0.05) and established the nomogram predicting 3- and 5-year RFS. The C-index and calibration curves of the nomogram demonstrated a close correlation between predicted and actual RFS. Patients were divided into high- and low-risk groups according to the model of RFS. Combining clinical parameters and immunohistochemical markers, we developed a robust nomogram to predict RFS after surgery for early-onset EC patients. This nomogram can predict prognosis well and guide treatment decisions.

Population pharmacokinetics and exposure-response relationships of dostarlimab in primary advanced or recurrent endometrial cancer in part 1 of RUBY.

Dostarlimab-gxly is a humanized monoclonal antibody of the IgG4 isotype that binds to the programmed cell death protein-1 (PD-1) receptor and blocks its ligands. RUBY (NCT03981796) is a two-part multicentre study in patients with recurrent or primary advanced endometrial cancer. The overall aims were to characterise the population pharmacokinetics (PopPK) from Part 1 of this study, identify relevant covariates of interest, and assess exposure-efficacy/safety (ER) relationships. A PopPK model developed using GARNET (NCT02715284) study data for dostarlimab monotherapy was externally validated with RUBY Part 1 study data. Subsequently, the model was updated with data across the two studies. Exposure-safety analyses for adverse events related to dostarlimab alone or in combination with standard of care (SOC) were modelled using logistic regression. Exposure-efficacy analysis included Cox proportional hazards analysis of the primary efficacy endpoint of progression-free survival (PFS). For the model update, 7957 pharmacokinetics observations from 868 patients pooled from both RUBY and GARNET studies were available. The model was consistent with the previous model. Dostarlimab clearance was estimated to be 7.79% lower when dostarlimab was given as SOC combination therapy. However, no significant covariates were clinically relevant. Hepatic or renal impairment did not affect pharmacokinetics. Among the safety endpoints, only rash showed a small yet statistically significant effect (P < .05) in all subjects; however, this was not not deemed clinically relevant. There were no other clinically significant exposure-safety or exposure-PFS relationships. The addition of chemotherapy to dostarlimab had limited effect on dostarlimab PopPK, with no clinically significant covariates or clinically relevant exposure-safety or exposure-PFS relationships.

The long-term clinical efficacy and safety of lenvatinib plus pembrolizumab in endometrial cancer: data from routine clinical practice in Russia

Background. Endometrial cancer (EC) treatment outcomes need to be improved. Immunotargeted therapy lead to long-term and delayed effects compared to chemotherapy. Estimation of long-term efficacy and quality of life are crucial when we are talking about efficacy in whole.Aim. To evaluate the long-term clinical efficacy of lenvatinib plus pembrolizumab therapy in patients with EC.Materials and methods. The study included 43 patients with stages I-IV EC with mismatch repair-proficient tumors and treatment duration of more than 9 months. We evaluated median progression-free survival, objective response, duration of treatment depending on the line of therapy, prevalence and type of adverse events, and correction regimens. Results. Lenvatinib plus pembrolizumab treatment was safe and efficacious in recurrent EC. Median of progression-free survival (patients with response or stabilization more than 9 months) is 10.2 months (95 % confidence interval 9.1-13.0), median of follow up is 9.7 (1.4-33.8) months. There were no complete responses, partial response was in 12 (28 %) patients, disease stabilization was in 31 (72 %) patients. Regarding safety, the overall rate of any-grade adverse events was 56.3 %. The most common treatment-related adverse events were fatigue (32.6 %), hypertension (23.3 %), and hypothyroidism (18.6 %). Dose reduction was performed in 22 (51.2 %) patients.Conclusion. The combination of lenvatinib plus pembrolizumab has long-term efficacy and manageable profile of safety. The presence of a significant pool of patients with durable response allows improving the survival rate of such patients in Russia.

Application and evaluation of minimally invasive surgical treatment options for early endometrial cancer.

Laparoscopic and robotic-assisted techniques have gained popularity, and endometrial cancer (EC) remains a significant health problem among women. Minimally invasive surgical (MIS) therapy options for early endometrial cancer will be evaluated for their effectiveness and safety is the aim of this paper. We also investigate the differences in oncologic outcomes between MIS and open surgery (OS) for individuals with early-stage EC. The patient was diagnosed with early-stage EC and treated with laparoscopic surgery and was the focus of a retrospective analysis. 162 patients with early EC were analyzed, with diagnoses occurring between 2002 and 2022. The patients were fragmented into two groups, one for OS and another for laparoscopic procedures. The total tumor excision and recurrence rates were identical across the two methods, indicating similar oncologic results. Rates of complications were likewise comparable across the two groups. The quality of life ratings of patients with robotic-assisted surgery was higher than those with laparoscopic surgery. Sixty-two (62.2%) of the 162 patients in this research had OS, whereas Fifty-six (57.8%) had MIS. The probability of recurrence of EC from stages III to IV was significanitly higher in women who had OS. Minimally invasive procedures were shown to be effective in treating early-stage EC, and while these findings provide support for their usage, larger multicenter randomized controlled studies are required to verify these results and further examine possible long-term advantages. Patients with early-stage EC, regardless of histologic type, had superior survival rates with MIS compared to OS.

Relationship Between p53 and Recurrence in Endometrial Cancer

Objective: Tumor protein 53 (p53), were included in the new FIGO 2023 staging system. Tumor protein 53 (p53) was incorporated into the new FIGO 2023 staging system. This study aimed to assess recurrence rates, overall survival (OS), and progression-free survival (PFS) in endometrial cancer patients with p53 mutations treated in the radiation oncology clinic. Material and Method: 260 patients were included in the study. The patients were divided into 2 groups according to the p53 mutation: p53 abnormal (p53 mutant) and p53 wild type. The Kaplan-Meier method was used to evaluate OS and PFS. Survival rates; were compared in terms of p53 mutations. Patients who underwent surgery for EC between January 1, 2008, and January 1, 2023, were included if their postoperative pathology reports evaluated p53 mutations, and they were referred to the radiation oncology clinic. Results: In our study; OS of EC was 84.2%, PFS was 88.8%. Total of 29 patients (%11.2) with recurrence were detected in the follow-up of the patients. The OS of p53 wild type patients was 88.6% and p53 mutant patients was 61% (p