Brian M. Slomovitz

Phase II Trial of Ribociclib Plus Letrozole in Women With Recurrent Low-Grade Serous Carcinoma of the Ovary, Fallopian Tube, or Peritoneum: A GOG Partners Trial (GOG 3026)

PURPOSE Low-grade serous carcinoma (LGSOC) of the ovary, fallopian tube, or peritoneum is a hormonally driven, relatively chemoresistant malignancy with limited treatment options in the recurrent setting. Given frequent estrogen receptor (ER) expression and dysregulation of the cyclin-dependent kinases 4 and 6 (CDK4/6)–p16–Rb pathway, features shared with hormone receptor–positive breast cancer, dual endocrine, and CDK4/6 inhibition is a biologically rational strategy. This phase II trial evaluated ribociclib plus letrozole in recurrent LGSOC. METHODS This open-label, single-arm, multicenter phase II study enrolled women with measurable, recurrent LGSOC. Patients received ribociclib (600 mg orally, once daily, days 1-21 of a 28-day cycle) and letrozole (2.5 mg orally, once daily). The primary end point was investigator-assessed objective response rate (ORR) per RECIST 1.1. Secondary end points included clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS Of 74 patients screened, 51 were enrolled and 49 treated. The confirmed ORR was 30.6% (90% CI, 19.9 to 43.2), including one complete and 14 partial responses. Among responders, the median duration of response was 21.2 months. The CBR was 84% (90% CI, 72.5 to 91.6). The median PFS was 14.5 months (90% CI, 10.1 to 28.8), and the median OS was 44.5 months (90% CI, 31.8 to not reached). The most common grade ≥3 adverse event (AE) was neutropenia (47%), managed with dose modifications. Three grade 5 events (6%) occurred but were unrelated to treatment. Treatment discontinuation because of AEs occurred in 4%. No dose-limiting toxicities were observed. CONCLUSION Ribociclib plus letrozole met the primary end point, achieving meaningful response rates and durable disease control in recurrent LGSOC. The safety profile was consistent with prior CDK4/6 inhibitor studies. This combination represents a therapeutic option in this rare and genomically distinct subtype.

Repurposing Food and Drug Administration-approved cancer therapies: exploring endocrine and targeted pathways in low-grade serous ovarian cancer treatment

Low-grade serous ovarian cancer is a rare epithelial ovarian cancer with limited responsiveness to conventional chemotherapy, particularly, in advanced or recurrent settings. Low-grade serous ovarian cancer is characterized by an indolent growth pattern and a high prevalence of mitogen-activated protein kinase pathway alterations (KRAS, BRAF, NRAS) and hormone receptor positivity, highlighting the potential for targeted therapies. MEK inhibitors (eg, trametinib, binimetinib) specifically target the mitogen-activated protein kinase pathway, whereas endocrine therapies and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors exploit hormone-driven pathways. This review explores the repurposing of the therapeutic potential of both MEK inhibitors and breast cancer therapies, as endorsed by the National Comprehensive Cancer Network, to improve outcomes in low-grade serous ovarian cancer. This review synthesizes evidence supporting the repurposing of MEK inhibitors and breast cancer therapies (endocrine therapies, CDK4/6 inhibitors, and mammalian target of rapamycin inhibitors) as treatment approaches for low-grade serous ovarian cancer. Trametinib significantly improved progression-free survival in the GOG 281 trial, establishing MEK inhibition as a key therapeutic option. In addition, molecular similarities in estrogen receptor/progesterone receptor, phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin, and CDK4/6 pathways between low-grade serous ovarian cancer and breast cancer provide a strong rationale for therapeutic crossover. Endocrine therapies demonstrated efficacy in low-grade serous ovarian cancer, particularly when combined with targeted agents to address resistance mechanisms. CDK4/6 inhibitors showed promise by blocking cell cycle progression and enhancing the response to endocrine therapies. In addition, mammalian target of rapamycin inhibitors have yielded clinical benefits in selected patients, emphasizing the importance of biomarker-driven treatment. Repurposing MEK inhibitors and endocrine-based approaches is shaping the treatment landscape for low-grade serous ovarian cancer, particularly in recurrent or advanced cases with limited treatment options. However, the variability in pathway alterations necessitates precise molecular profiling and optimized combination strategies. Future studies leveraging patient-derived models and advanced profiling techniques are critical for refining these approaches. These efforts may help expand National Comprehensive Cancer Network-endorsed options, and provide new hope for patients with hormone-sensitive low-grade serous ovarian cancer.

Updates in the Use of Targeted Therapies for Gynecologic Cancers

Targeted therapies have changed the treatment landscape in gynecologic cancer. Studies released over the past year have led to the incorporation of immunotherapy (IO) into the treatment for all patients with endometrial and cervical cancers at some point during their disease course. Poly(ADP-ribose) polymerase (PARP) inhibitors continue to play a role in women with ovarian carcinoma, particularly in homologous repair deficient tumors. Furthermore, the benefit of PARP inhibitors in challenging subgroups continues to be elucidated. Biomarker identification has led to the approval or compendium listing of several antibody-drug conjugates (ADCs). This review will update on IO, ADCs, and PARP inhibition for the treatment of gynecologic cancers.

Adding immunotherapy to first-line treatment of advanced and metastatic endometrial cancer

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. 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. 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. 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.

ENGOT-EN20/GOG-3083/XPORT-EC-042 – A phase III, randomized, placebo-controlled, double-blind, multicenter trial of selinexor in maintenance therapy after systemic therapy for patients with p53 wild-type, advanced, or recurrent endometrial carcinoma: rationale, methods, and trial design

Patients with advanced/recurrent endometrial cancer have a poor prognosis and limited treatment options. Biomarkers such as tumor protein 53 ( To evaluate the efficacy of selinexor compared with placebo as maintenance therapy in patients with advanced or recurrent Selinexor administered at 60 mg weekly as maintenance therapy will show manageable safety and maintain efficacy in patients with This is a prospective, multicenter, double-blind, placebo-controlled, randomized phase III study designed to evaluate the efficacy and safety of selinexor as a maintenance therapy in patients with advanced or recurrent Eligible patients must have histologically confirmed endometrial cancer, The primary endpoint is investigator-assessed progression-free survival per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in the intent-to-treat population. A total of 220 patients will be enrolled. Accrual is expected to be completed in 2024 with presentation of results in 2025. NCT05611931.

The promise of combining CDK4/6 inhibition with hormonal therapy in the first-line treatment setting for metastatic or recurrent endometrial adenocarcinoma

Metastatic or recurrent endometrioid adenocarcinoma of the uterine corpus is often incurable with limited treatment options. First-line treatment often includes cytotoxic chemotherapy, which incurs significant toxicities for many patients. Endometrial cancer, specifically endometrioid cancer, is a hormone-sensitive disease and, while single-agent hormonal therapies have demonstrated clinical benefit, resistance to these agents often leads to the use of chemotherapy. There is a lack of approved endocrine treatment options in the metastatic setting for most recurrent endometrial cancers, representing an unmet clinical need. Emerging evidence suggests that hormonal therapy in combination with other targeted treatments, such as cyclin dependent kinase (CDK)4/6 inhibitors, is well tolerated and effective in select patient populations. We discuss the clinical evidence suggesting that the combination of CDK4/6 inhibitors and hormonal therapy has the potential to represent an important addition to the first-line treatment options for patients with low-grade advanced or recurrent endometrial cancer.

Homologous recombination deficiency in endometrial cancer: shedding light on recent clinical findings

Endometrial cancer is the most common gynecologic malignancy in the United States, with rising incidence and high recurrence rates. Immune checkpoint inhibitors (ICIs) benefit patients with mismatch repair-deficient (dMMR) tumors, but options remain limited for those with mismatch repair-proficient (pMMR) disease. Homologous recombination deficiency (HRD), a genomic instability phenotype, has emerged as a therapeutic target. Poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPis) are being investigated in endometrial cancer, with studies exploring whether HRD predicts response, particularly in combination with ICIs or chemotherapy. This review examines HRD in endometrial cancer, focusing on its molecular basis, clinical implications, and emerging therapeutic strategies. HRD occurs in a sub-set of endometrial cancers, particularly non-endometrioid sub-types, and is linked to genomic instability and platinum sensitivity. The Cancer Genome Atlas (TCGA) molecular classification has improved understanding of HRD prevalence across sub-types. HRD testing remains challenging due to a lack of standardization, with current methods including genomic-scar assays, next-generation sequencing, and functional assays. Clinical trials, such as DUO-E and RUBY-2, suggest that PARPi combined with ICIs or chemotherapy may improve outcomes in pMMR tumors, whereas PARPi monotherapy offers limited benefits. Resistance to PARPi is common, driven by the restoration of homologous recombination repair, replication fork stabilization, and drug efflux. HRD is a promising biomarker and therapeutic target in endometrial cancer. Evidence supports the integration of PARPi for select populations, although further research is needed to refine testing, optimize patient selection, and overcome resistance. Future trials should prioritize predictive biomarkers and novel combinations to maximize the benefits of PARPi in HRD endometrial cancer.

Checkpoint inhibitor rechallenge in advanced endometrial cancer: revisiting the immune landscape beyond first-line therapy

The integration of immune checkpoint inhibitors into frontline therapy for advanced or recurrent endometrial cancer has transformed treatment paradigms, particularly for patients with mismatch repair-deficient (dMMR) tumors. However, this advancement has introduced a pressing clinical challenge: how to manage patients who experience disease progression following exposure to a prior immune checkpoint inhibitor. Despite the absence of prospective guidance, immune checkpoint inhibitor rechallenge is already occurring in clinical practice. Notably, 35% of patients in the dostarlimab arm of the RUBY trial received subsequent immunotherapy off-protocol, highlighting the gap between evolving clinical behavior and available evidence. Emerging retrospective data suggest that retreatment with immune checkpoint inhibitors may be clinically and biologically plausible, particularly in biomarker-enriched populations. In a study, 54.5% of patients with dMMR endometrial cancer responded to second-line immune checkpoint inhibitor rechallenge, including complete responses. Additional reports indicate that combining immune checkpoint inhibitors with anti-vascular endothelial growth factors or multi-kinase inhibitors, such as lenvatinib or cabozantinib, may enhance immune reactivation even in microsatellite-stable or carcinosarcoma histologies. Nonetheless, toxicity remains a concern, with grade 3 to 4 immune-related adverse events and high rates of dose modification reported. Mechanistic insights point to immune escape pathways, including vascular endothelial growth factor-driven immunosuppression, MLH1 methylation, and high subclonal neoantigen burden, as contributors to immune checkpoint inhibitor resistance. These findings support the use of rational combinations and novel targets. Prospective trials such as NRG-GY025 are now evaluating dual checkpoint blockade in immune checkpoint inhibitor-pretreated dMMR endometrial cancer. In contrast, synthetic lethality strategies, such as the Werner helicase inhibitor HRO761 in high microsatellite instability tumors, represent promising non-immune-based rechallenge approaches. As immune checkpoint inhibitor exposure becomes commonplace in earlier treatment settings, there is an urgent need for biologically informed, individualized strategies to guide post-immune checkpoint inhibitor management. Future progress will depend on refining rechallenge criteria, optimizing combination regimens, and developing predictive biomarkers to identify patients most likely to benefit from retreatment.

Evolving treatment paradigms in metastatic or recurrent low-grade endometrial cancer: When is hormonal-based therapy the preferred option?

Endometrial cancer is the most common gynecologic malignancy in developed countries, with increasing incidence and mortality rates worldwide. While most cases are successfully treated with surgery, first-line treatment options for metastatic or recurrent endometrial cancer involve significant toxicities. Imprecise classification of heterogeneous subgroups further complicates treatment decisions and interpretation of clinical trial results. Recent advances in molecular classification are guiding treatment decisions for metastatic or recurrent endometrial cancers. Integrating molecular characteristics with traditional clinicopathology can both reduce overtreatment or undertreatment and help guide the appropriate choice of therapies and effective design of future studies. Here we discuss the treatment of metastatic or recurrent low-grade endometrioid adenocarcinoma of the uterine corpus, which is distinct from high-grade tumors histologically, molecularly, and in treatment response.

Immunotherapy in endometrial cancer

The Cancer Genome Atlas (TCGA) endometrial cancer data expanded our knowledge about the role of different immunotherapeutic approaches based on molecular subtypes. Immune checkpoint inhibitors demonstrated distinct antitumor activities as monotherapy or in combination. In microsatellite unstable (microsatellite instability-high) endometrial cancer, immunotherapy with immune checkpoint inhibitors showed promising single agent activity in recurrent settings. Different strategies are needed to enhance the response or reverse resistance to immune checkpoint inhibitors, or both, in microsatellite instability-high endometrial cancer. On the other hand, single immune checkpoint inhibitors showed underwhelming efficacy in microsatellite stable endometrial cancer but this was significantly improved using a combination approach. Furthermore, studies are also needed to improve response along with ensuring safety and tolerability in microsatellite stable endometrial cancer. This review summarizes the current indications of immunotherapy for the treatment of advanced and recurrent endometrial cancer. We also outline potential future strategies for an immunotherapy based combination approach in endometrial cancer to combat resistance or enhance response to immune checkpoint inhibitors, or both.

Low-grade serous ovarian cancer: expert consensus report on the state of the science

Compared with high-grade serous carcinoma, low-grade serous carcinoma of the ovary or peritoneum is a less frequent epithelial ovarian cancer type that is poorly sensitive to chemotherapy and affects younger women, many of whom endure years of ineffective treatments and poor quality of life. The pathogenesis of this disease and its management remain incompletely understood. However, recent advances in the molecular characterization of the disease and identification of novel targeted therapies with activity in low-grade serous carcinoma offer the promise of improved outcomes. To update clinicians regarding recent scientific and clinical trial advancements and discuss unanswered questions related to low-grade serous carcinoma diagnosis and treatment, a panel of experts convened for a workshop in October 2022 to develop a consensus document addressing pathology, translational research, epidemiology and risk, clinical management, and ongoing research. In addition, the patient perspective was discussed. The recommendations developed by this expert panel-presented in this consensus document-will guide practitioners in all settings regarding the clinical management of women with low-grade serous carcinoma and discuss future opportunities to improve research and patient care.

Comprehensive management of vulvovaginal cancers

AbstractVulvar and vaginal cancers represent rare malignancies, with an incidence of 2.7 per 100,000 women for vulvar cancer, predominantly affecting women older than 60 years, although rising rates are observed in younger demographics. Approximately 90% of vulvar cancers are squamous cell carcinoma and frequently are associated with human papillomavirus (HPV) infection. Vaginal cancer, constituting less than 1% of all female cancers, similarly exhibit HPV‐related trends. This review delineates the etiology, histopathology, and treatment strategies for carcinomas and vulvovaginal melanomas and sarcomas. Surgical intervention remains the primary treatment modality for vulvar cancer, involving tumor resection and inguinofemoral lymph node staging. For locally advanced vulvar carcinoma, chemoradiation is advised when exenterative surgery would be indicated. Recurrence rates within 2 years after diagnosis range from 12% to 37%. Unfortunately, systemic treatments for recurrent or metastatic disease are limited, with 5‐year survival rates at approximately 20%. Current evidence primarily derives from retrospective studies or small phase 2 trials or otherwise is extrapolated from the treatment of cervical cancer. Enrollment in clinical trials is strongly advocated, along with prompt access to best supportive care to mitigate the effect of locoregional progression on quality of life. Moreover, the psychosocial implications of treatment on body image and sexuality necessitate careful consideration. Future HPV vaccination initiatives may reduce cancer incidence, although significant effects of such vaccination will manifest over decades, underscoring the urgent need to enhance treatment efficacy and minimize morbidity in vulvar and vaginal cancers.

First-line lenvatinib plus pembrolizumab versus chemotherapy for advanced endometrial cancer: 1-Year follow-up after final analysis of the ENGOT-en9/LEAP-001 phase 3 trial

The phase 3 ENGOT-en9/LEAP-001 trial (NCT03884101) comparing first-line lenvatinib+pembrolizumab with carboplatin+paclitaxel did not meet pre-specified statistical criteria for overall survival or progression-free survival in participants with advanced/recurrent endometrial cancer. We report results after an additional year of follow-up (overall median 54.5 [range; 46.5-69.0] months). Eligible participants were adult females with stage III to IV or recurrent, histologically confirmed endometrial cancer. Measurable or non-measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and radiographically apparent disease per blinded independent central review was required. Participants were randomly allocated 1:1 to lenvatinib+pembrolizumab or chemotherapy (paclitaxel+carboplatin). The primary end points were overall survival and progression-free survival per RECIST version 1.1 by blinded independent central review. Secondary end points included objective response rate per RECIST version 1.1 by blinded independent central review and safety. The median overall survival (95% confidence interval [CI]) was 30.9 (range; 25.4-37.6) months with lenvatinib+pembrolizumab versus 29.4 (range; 26.2-34.8) months with chemotherapy in mismatch repair-proficient endometrial cancer (hazard ratio [HR] 0.99, 95% CI 0.82 to 1.21), 37.9 (range; 32.2-43.0) versus 32.3 (range; 27.2-35.7) months in all-comers (HR 0.91, 95% CI 0.77 to 1.09), and not reached in either treatment group in mismatch repair-deficient endometrial cancer (HR 0.60, 95% CI 0.39 to 0.93]). Corresponding results for progression-free survival were 9.6 (range; 8.2-11.9) versus 10.2 (range; 8.4-10.5) months (HR 1.01, 95% CI 0.83 to 1.22), 12.5 (range; 10.3-15.1) versus 10.2 (range; 8.4-10.4) months (HR 0.92, 95% CI 0.77 to 1.10]), and 31.8 (22.5 to not reached) versus 9.0 (range; 8.2-17.1) months (HR 0.62, 95% CI 0.41-0.93). Objective response rates were 50.6% versus 54.7%, 55.7% versus 55.5%, and 72.0% versus 58.0%, respectively. No new safety signals were identified. The results were consistent with those at the final analysis. The mismatch repair-proficient, all-comer, and mismatch repair-deficient populations continued to demonstrate antitumor activity for lenvatinib+pembrolizumab after an additional year of follow-up. These results should be interpreted with caution due to the exploratory nature of the analysis. ClinicalTrials.gov No. NCT03884101.

Validation of comprehensive genomic profiling for prognostic and potential therapeutic molecular classification of endometrial cancer

We sought to validate the prognostic utility of comprehensive genomic profiling (CGP)-based molecular stratification for patients with endometrial carcinoma and to assess co-occurring biomarkers across subtypes. This study included patients from a de-identified nationwide (US-based) endometrial cancer clinicogenomic database who underwent CGP testing as part of routine care. Molecular subtypes were classified as POLE mutated (POLEmut), MSI-H, TP53 mutated (TP53mut), and no specific molecular profile (NSMP). Time to next treatment and overall survival were compared between molecular subtypes, with multivariable Cox models adjusted for relevant covariables. Of 1,139 evaluated patients with advanced or recurrent endometrial carcinoma, the prevalence of the 4 molecular subtypes was 1% POLEmut, 22% high microsatellite instability, 47% TP53mut, and 31% NSMP. Compared with NSMP patients, POLEmut patients had numerically more favorable time to next treatment (HR 0.50, 95% CI 0.21 to 1.21) and overall survival (HR 0.52, 95% CI 0.17 to 1.66). High microsatellite instability patients had similar time to next treatment (HR 1.08, 95% CI 0.89 to 1.30) and overall survival (HR 0.91, 95% CI 0.71 to 1.19) relative to NSMP patients. TP53mut patients had the least favorable outcomes for time to next treatment (compared with NSMP, HR 1.39, 95% CI 1.19 to 1.62) and overall survival (HR 2.15, 95% CI 1.77 to 2.61). In multivariable analysis, TP53mut status was associated with less favorable time to next treatment and overall survival. Frequencies of other biomarkers varied by molecular subtype. The Cancer Genome Atlas (TCGA)/Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) molecular classifier for endometrial carcinoma can be recapitulated using CGP and provides prognostic stratification even within an advanced or recurrent disease cohort. CGP for molecular subclassification could support trial design and enrollment and inform treatment escalation or selection.

Pembrolizumab or Placebo Plus Adjuvant Chemotherapy With or Without Radiotherapy for Newly Diagnosed, High-Risk Endometrial Cancer: Results in Mismatch Repair-Deficient Tumors

Mismatch repair-deficient (dMMR) endometrial cancer (EC) is an inflamed phenotype with poor outcomes when meeting high-risk criteria and limited treatment options in the adjuvant setting. We report protocol-prespecified subgroup analysis of patients with dMMR tumors from the phase III ENGOT-en11/GOG-3053/KEYNOTE-B21 study (ClinicalTrials.gov identifier: NCT04634877 ) in newly diagnosed, high-risk EC after surgery with curative intent. Patients were randomly assigned to pembrolizumab 200 mg or placebo (six cycles) plus carboplatin-paclitaxel (four to six cycles) once every 3 weeks, then pembrolizumab 400 mg or placebo once every 6 weeks (six cycles), respectively. MMR status was a stratification factor. Patients received radiotherapy at investigator discretion. Investigator-assessed disease-free survival (DFS) was a primary end point. No formal hypothesis testing was performed for subgroup analysis. In the intention-to-treat population, 141 patients in the pembrolizumab arm and 140 in the placebo arm had dMMR tumors. At this interim analysis, hazard ratio for DFS favored pembrolizumab (0.31 [95% CI, 0.14 to 0.69]); median DFS was not reached in either group. Two-year DFS rates were 92.4% (95% CI, 84.4 to 96.4) and 80.2% (95% CI, 70.8 to 86.9), respectively. No new safety signals occurred. Longer-term follow-up of outcomes will be evaluated at final analysis. Preplanned subgroup analysis on the basis of the study's stratification factors suggests that pembrolizumab plus chemotherapy improves DFS and is clinically relevant for patients with dMMR tumors in the curative-intent setting.

Tisotumab vedotin in Japanese patients with recurrent or metastatic cervical cancer: results from the innovaTV 301/ENGOT-cx12/GOG-3057 trial

Tisotumab vedotin resulted in significantly longer overall survival compared with chemotherapy as second- or third-line therapy for recurrent or metastatic cervical cancer in the phase III, multi-national, open-label innovaTV 301/ENGOT-cx12/GOG-3057 trial. We report the results of a sub-group analysis of enrolled Japanese patients. Patients were randomized 1:1 to tisotumab vedotin or investigator-choice chemotherapy (topotecan [nogitecan hydrochloride], vinorelbine, gemcitabine, irinotecan, or pemetrexed). The primary end point was overall survival. Among 502 randomized patients, 101 were Japanese (tisotumab vedotin, n = 50; chemotherapy, n = 51). With 13.7 months of median follow-up in Japanese patients, median overall survival was 15.0 months (95% confidence interval [CI] 9.7 to not estimable) with tisotumab vedotin and 8.5 months (95% CI 6.8 to 10.6) with chemotherapy, representing a 55% lower risk of death with tisotumab vedotin than chemotherapy (hazard ratio 0.45, 95% CI 0.27 to 0.77). Median progression-free survival was 4.0 months (95% CI 3.0 to 4.4) with tisotumab vedotin and 2.0 months (95% CI 1.5 to 3.0) with chemotherapy (hazard ratio 0.63, 95% CI 0.42 to 0.95). The confirmed objective response rate was 24.0% (95% CI 13.1 to 38.2) with tisotumab vedotin and 2.0% (95% CI 0.0 to 10.4) with chemotherapy. All patients in the tisotumab vedotin and chemotherapy arms had ≥1 treatment-emergent adverse event; grade ≥3 events occurred in 42.9% and 66.0%, respectively. Six patients (12.2%) discontinued tisotumab vedotin due to treatment-emergent adverse events. Consistent with global findings, tisotumab vedotin resulted in clinical improvement compared with chemotherapy across all efficacy end points, and demonstrated a manageable adverse event profile in Japanese patients with recurrent or metastatic cervical cancer.

Selinexor in Maintenance Therapy After Systemic Therapy for Participants With p53 Wild-Type, Advanced or Recurrent Endometrial Carcinoma

The purpose of this study is to evaluate the efficacy and safety of selinexor as a maintenance treatment in patients with p53 wt endometrial carcinoma (EC), who have achieved a partial response (PR) or complete response (CR) (per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v 1.1\]) after completing at least 12 weeks of platinum-based therapy. A total of 276 participants will be enrolled in the study and randomized in a 1:1 ratio to maintenance therapy with either selinexor or placebo.

Durvalumab With or Without Olaparib as Maintenance Therapy After First-Line Treatment of Advanced and Recurrent Endometrial Cancer

A study to assess the efficacy and safety of durvalumab in combination with platinum-based chemotherapy (paclitaxel + carboplatin) followed by maintenance durvalumab with or without olaparib for patients with newly diagnosed advanced or recurrent endometrial cancer.

Atezolizumab Trial in Endometrial Cancer - AtTEnd

Atezolizumab is an engineered humanised monoclonal immunoglobulin G1 antibody that binds selectively to PD-L1 and prevents its interaction with PD-1 and B7-1. In May 2016 atezolizumab was approved by the FDA for patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following any platinum-containing chemotherapy, or within 12 months of receiving chemotherapy before surgery (neoadjuvant) or after surgery (adjuvant); in October 2016 it was approved by the FDA for patients with metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following platinum-containing chemotherapy, and have progressed on an appropriate FDA-approved targeted therapy if their tumor has EGFR or ALK gene abnormalities. Finally, in April 2017 atezolizumab was granted accelerated approval by FDA for the first-line treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin chemotherapy. Combinations of atezolizumab with chemotherapeutic agents and/or targeted therapies were studied in different solid tumors such as melanoma, NSCLC, renal cell carcinoma and colorectal carcinoma. From these studies the AE profile of atezolizumab combinations were consistent with that of the individual agents. Finally, preliminary results of a Phase Ia study of Atezolizumab (NCT01375842) monotherapy in relapsed endometrial cancer were reported as abstract at ASCO 2017. Fifteen patients were evaluated for safety and efficacy with a minimum follow-up of 11.2 months. No G4-5 related AEs occurred. Regarding efficacy ORR was 13% \[2/15\] by RECIST. Atezolizumab seemed to have a favorable safety profile, with durable clinical benefit in some patients. Further studies with atezolizumab are warranted given its promising results in advanced endometrial cancer and the limited efficacy of current treatment options.