Real-world use of immune checkpoint inhibitors in advanced or recurrent endometrial cancer.

Objective: The aim of this study was to describe real-world use of immune checkpoint inhibitors for women with advanced or recurrent endometrial cancer.

Methods: Adult women with advanced or recurrent endometrial cancer who received at least one line of systemic treatment between January 1, 2014 and November 1, 2020, then followed to May 31, 2021 in a nationwide electronic health record-derived de-identified database. Chi-Squared test or Welch's 2-sample t-tests were used to compare patient and clinical factors associated with immune checkpoint inhibitor treatment.

The association of histopathologic features after neoadjuvant chemo-immunotherapy with clinical outcome: Sub-analyses from the randomized double-blinded, placebo-controlled, Phase III IMagyn050/GOG3015/ENGOT-ov39 study.

Objective: Histopathologic characteristics after neoadjuvant chemotherapy (NACT) may correlate with outcome. This study evaluates histopathologic features after immunotherapy and NACT/bevacizumab, and associated clinical outcomes.

Methods: Evaluable tissue from IMagyn050/GOG3015/ENGOT-ov39 patients from prespecified anatomic sites from interval cytoreductive surgery (ICS) after NACT/bevacizumab plus atezolizumab/placebo underwent central histopathologic scoring and analyzed with clinical outcomes.

Overall survival and patient-reported outcome results from the placebo-controlled randomized phase III IMagyn050/GOG 3015/ENGOT-OV39 trial of atezolizumab for newly diagnosed stage III/IV ovarian cancer.

Objective: To determine the impact on overall survival (OS) and patient-reported outcomes (PROs) of combining atezolizumab with standard therapy for newly diagnosed stage III/IV ovarian cancer.

Methods: The placebo-controlled double-blind randomized phase III IMagyn050/GOG 3015/ENGOT-OV39 trial (NCT03038100) assigned eligible patients to 3-weekly atezolizumab 1200 mg or placebo for 22 cycles with platinum-based chemotherapy and bevacizumab. Coprimary endpoints were progression-free survival (already reported) and OS in the PD-L1-positive and intent-to-treat (ITT) populations, tested hierarchically.

Temporal Patterns and Adoption of Germline and Somatic BRCA Testing in Ovarian Cancer.

Objective: To describe the testing rate, patient characteristics, temporal trends, timing, and results of germline and somatic BRCA testing in patients with ovarian cancer using real-world data.

Methods: We included a cross-sectional subset of adult patients diagnosed with ovarian cancer between January 1, 2011, and November 30, 2018, who received frontline treatment and were followed for at least 1 year in a real-world database. The primary outcome was receipt of BRCA testing, classified by biosample source as germline (blood or saliva) or somatic (tissue).

Atezolizumab, Bevacizumab, and Chemotherapy for Newly Diagnosed Stage III or IV Ovarian Cancer: Placebo-Controlled Randomized Phase III Trial (IMagyn050/GOG 3015/ENGOT-OV39).

Purpose: To evaluate the addition of the humanized monoclonal antiprogrammed death ligand-1 (PD-L1) antibody, atezolizumab, to platinum-based chemotherapy and bevacizumab in newly diagnosed stage III or IV ovarian cancer (OC).

Methods: This multicenter placebo-controlled double-blind randomized phase III trial (ClinicalTrials.gov identifier: NCT03038100) enrolled patients with newly diagnosed untreated International Federation of Gynecology and Obstetrics (FIGO) stage III or IV OC who either had undergone primary cytoreductive surgery with macroscopic residual disease or were planned to receive neoadjuvant chemotherapy and interval surgery.

Immune Activation in Patients with Locally Advanced Cervical Cancer Treated with Ipilimumab Following Definitive Chemoradiation (GOG-9929).

Purpose: A phase I clinical trial (GOG-9929) examined the safety and efficacy of adjuvant immune-modulation therapy with the checkpoint inhibitor ipilimumab [anti-CTL antigen-4 (anti-CTLA-4)] following chemoradiation therapy (CRT) for newly diagnosed node-positive human papillomavirus (HPV)-related cervical cancer. To better understand the mechanism of action and to identify predictive biomarkers, immunologic and viral correlates were assessed before, during, and after treatment.

Patients And Methods: Twenty-one patients who received CRT and ≥2 doses of ipilimumab and 5 patients who received CRT only were evaluable for translational endpoints.

Safety and Clinical Activity of Atezolizumab Plus Bevacizumab in Patients with Ovarian Cancer: A Phase Ib Study.

Purpose: Atezolizumab has shown antitumor activity in patients with ovarian cancer. Dual blockade of programmed death-ligand 1 (PD-L1) and VEGF enhances anticancer immunity and augments antitumor activity in several cancers. The safety and efficacy of atezolizumab plus bevacizumab were evaluated in patients with ovarian cancer.

Non-coding somatic mutations converge on the PAX8 pathway in ovarian cancer.

The functional consequences of somatic non-coding mutations in ovarian cancer (OC) are unknown. To identify regulatory elements (RE) and genes perturbed by acquired non-coding variants, here we establish epigenomic and transcriptomic landscapes of primary OCs using H3K27ac ChIP-seq and RNA-seq, and then integrate these with whole genome sequencing data from 232 OCs. We identify 25 frequently mutated regulatory elements, including an enhancer at 6p22.

Clinicopathological significance of endoplasmic reticulum stress proteins in ovarian carcinoma.

Epithelial ovarian cancer (EOC) is a leading cause of cancer-related mortality in the United States due to the late-stage disease at diagnosis. Overexpression of GRP78 and PDI following endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) promote growth and invasion in cancer. To identify novel prognostic biomarkers in EOC, here we determined the expression of ER stress-associated proteins (GRP78, ATF6 and PERK) and correlated with clinical outcome in EOC.

A Study of High-Grade Serous Ovarian Cancer Origins Implicates the SOX18 Transcription Factor in Tumor Development.

Fallopian tube secretory epithelial cells (FTSECs) are likely the main precursor cell type of high-grade serous ovarian cancers (HGSOCs), but these tumors may also arise from ovarian surface epithelial cells (OSECs). We profiled global landscapes of gene expression and active chromatin to characterize molecular similarities between OSECs (n = 114), FTSECs (n = 74), and HGSOCs (n = 394). A one-class machine learning algorithm predicts that most HGSOCs derive from FTSECs, with particularly high FTSEC scores in mesenchymal-type HGSOCs (p < 8 × 10).

Sequential Ipilimumab After Chemoradiotherapy in Curative-Intent Treatment of Patients With Node-Positive Cervical Cancer.

Importance: Despite standard chemoradiotherapy (CRT), most women with lymph node (LN)-positive cervical cancer experience disease recurrence. Immunotherapy is being investigated in the up-front treatment setting.

Objectives: To assess the safety of sequential immunotherapy after CRT and to investigate human papillomavirus (HPV) genotype and HLA allele status on survival and programmed cell death 1 (PD-1) expression before and after CRT and sequential immunotherapy.

Safety, clinical activity and biomarker assessments of atezolizumab from a Phase I study in advanced/recurrent ovarian and uterine cancers.

Objective: Patients with advanced/recurrent epithelial ovarian and uterine cancers have limited treatment options beyond platinum chemotherapy. Both tumor types can express programmed death-ligand 1 (PD-L1), providing a potential therapeutic target for these patients. Here we present data from the ovarian and uterine cancer cohorts of the Phase I atezolizumab monotherapy study (PCD4989g).

Predictive Value of FDG PET/CT to Detect Lymph Node Metastases in Cervical Cancer.

Purpose: The aim of this study was to determine the prognostic significance of PET/CT findings in women with cervical cancer and describe the normalization of lymph node SUVmax (nSUVmax).

Materials And Methods: A retrospective review was performed of 113 patients with cervical cancer who underwent a PET/CT before receiving definitive therapy. SUVmax measurements were normalized to the SUV of the pelvic blood pool.

Expression of protein disulfide isomerase family members correlates with tumor progression and patient survival in ovarian cancer.

Objective: Protein disulfide isomerase (PDI) is an oxidoreductase that is overexpressed in several cancers. PDI family members (PDIs) play a role in various diseases including cancer. Select PDIs were reported as useful markers in other cancers but their expression in ovarian cancer has not been thoroughly assessed.

Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial.

Background: HER2-targeted treatments have improved outcomes in patients with HER2-positive breast cancer in the neoadjuvant, adjuvant, and metastatic settings; however, some patients remain at risk of relapse or death for many years after treatment of early-stage disease. Therefore, new strategies are needed. We did a phase 3 trial to assess a neoadjuvant regimen for HER2-positive breast cancer that replaces traditional systemic chemotherapy with targeted treatment.

Endoplasmic reticulum stress in complex atypical hyperplasia as a possible predictor of occult carcinoma and progestin response.

Unlabelled: Glucose-regulated protein (GRP)-78, the key regulator of endoplasmic reticulum (ER) stress, is associated with endometrial cancer (EC) development and progression. However, its role in the continuum from complex atypical hyperplasia (CAH) to EC is unknown and the focus of this study.

Methods: 252 formalin-fixed, paraffin-embedded endometrial biopsies from patients with CAH diagnosed between 2003 and 2011 were evaluated for GRP78 expression by immunohistochemistry.

Glucose-regulated protein 94 deficiency induces squamous cell metaplasia and suppresses PTEN-null driven endometrial epithelial tumor development.

Endometrial carcinoma is the most prevalent gynecologic cancer in the United States. The tumor suppressor gene Pten (phosphatase and tensin homolog) is commonly mutated in the more common type 1 (endometrioid) subtype. The glucose-regulated protein 94 (GRP94) is emerging as a novel regulator for cancer development.

Dual Metronomic Chemotherapy with Nab-Paclitaxel and Topotecan Has Potent Antiangiogenic Activity in Ovarian Cancer.

There is growing recognition of the important role of metronomic chemotherapy in cancer treatment. On the basis of their unique antiangiogenic effects, we tested the efficacy of nab-paclitaxel, which stimulates thrombospondin-1, and topotecan, which inhibits hypoxia-inducible factor 1-α, at metronomic dosing for the treatment of ovarian carcinoma. In vitro and in vivo SKOV3ip1, HeyA8, and HeyA8-MDR (taxane-resistant) orthotopic models were used to examine the effects of metronomic nab-paclitaxel and metronomic topotecan.