Anti-Angiogenesis Therapy in Ovarian Cancer: Which Patient is It Most Likely to Benefit?

Angiogenesis is known to play an important role in normal ovarian physiology as well as in growth and progression of ovarian cancer. The first FDA approval of bevacizumab in 2004 was for metastatic colorectal cancer in combination with chemotherapy; this was a key point for several subsequent approvals of antiangiogenic drugs. The efficacy of bevacizumab treatment is modest, however, and most ovarian cancer patients eventually develop acquired resistance, which highlights the need for new targeted therapies and/or combination strategies.

Prospective pilot trial with combination of propranolol with chemotherapy in patients with epithelial ovarian cancer and evaluation on circulating immune cell gene expression.

Objective: To determine the feasibility of pharmacologic beta-adrenergic blockade in women with newly diagnosed stage II-IV epithelial ovarian cancer (EOC) throughout primary treatment.

Methods: Patients initiated propranolol prior to beginning chemotherapy or surgery. Feasibility was assessed as proportion able to complete 6 chemotherapy cycles while on adrenergic suppression.

Final Overall Survival of a Randomized Trial of Bevacizumab for Primary Treatment of Ovarian Cancer.

Purpose: We report the final, protocol-specified analysis of overall survival (OS) in GOG-0218, a phase III, randomized trial of bevacizumab in women with newly diagnosed ovarian, fallopian tube, or primary peritoneal carcinoma.

Methods: A total of 1,873 women with incompletely resected stage III to IV disease were randomly assigned 1:1:1 to six 21-day cycles of intravenous carboplatin (area under the concentration time curve 6) and paclitaxel (175 mg/m) versus chemotherapy plus concurrent bevacizumab (15 mg/kg, cycles 2 to 6) versus chemotherapy plus concurrent and maintenance bevacizumab (cycles 2 to 22). Inclusion criteria included a Gynecologic Oncology Group performance status of 0 to 2 and no history of clinically significant vascular events or evidence of intestinal obstruction.

Estimation of Actual and Ideal Bodyweight Using Morphometric Measurements of Miniature, Saddle-Type, and Thoroughbred Horses.

Adding breed type, height, and neck circumference to body length and girth circumference improves bodyweight (BW) estimation in different breeds of horses; however, equations have not been developed for all breed types. The objectives were to develop BW estimation equations for Miniature, saddle-type, and Thoroughbred horses using morphometric measurements. Measurements were collected on adult (≥3 years, nonpregnant) saddle-type (n = 209), adult (n = 249) and juvenile (<3 years, n = 61) Miniatures, and adult Thoroughbreds (n = 100).

Adaptive responses in a PARP inhibitor window of opportunity trial illustrate limited functional interlesional heterogeneity and potential combination therapy options.

Poly (ADP-ribose) polymerase inhibitor (PARPi)-based combination therapies are demonstrating efficacy in patients, however, identifying the right combination for the right patient remains a critical challenge. Thus, it is urgent to develop approaches able to identify patients likely to benefit from specific combination therapies. Several groups, including ours, have demonstrated that targeting adaptive responses induced by PARPi increases depth and duration of response.

Equine Fecal Microbiota Changes Associated With Anthelmintic Administration.

The gastrointestinal microbiota (GIM) plays an essential role in maintaining intestinal homeostasis with disruptions having profound effects on the wellbeing of the host animal. Parasitic infection is a long-standing issue for the equine industry, and the use of anthelmintic drugs for parasite control has long been standard practice. The impact of anthelmintic treatment on the GIM in healthy horses is not well known.

Advancing Drug Development in Gynecologic Malignancies.

Gynecologic malignancies continue to be a major cause of morbidity and mortality in the United States despite recent advances in oncologic therapies. To realize the promise of immunotherapy and biomarker-driven approaches to improve clinical outcomes for patients, better communication among stakeholders in the drug development and approval pathways is needed. To this end, the FDA-AACR-SGO Drug Development in Gynecologic Malignancies Workshop brought together clinicians, patient advocates, researchers, industry representatives, and regulators in June 2018, to review the state of the science in gynecologic cancers and explore how scientific advances impact approval processes.

Poly-ADP-ribose polymerase inhibitor use in ovarian cancer: expanding indications and novel combination strategies.

The use of poly(ADP-ribose) polymerase (PARP) inhibition is transforming care for the treatment of ovarian cancer, with three different PARP inhibitors (PARPi) gaining US Food and Drug Administration approval since 2014. Given the rapidly expanding use of PARPi, this review aims to summarize the key evidence for their use and therapeutic indications. Furthermore, we provide an overview of the development of PARPi resistance and the emerging role of PARPi combination therapies, including those with anti-angiogenic and immunotherapeutic agents.

Department of Defense end-of-season influenza vaccine effectiveness estimates for the 2017-2018 season.

The Department of Defense (DoD) generates influenza vaccine effectiveness (VE) estimates each season. The Armed Forces Health Surveillance Branch Air Force (AFHSB-AF) satellite, Naval Health Research Center Operational Infectious Disease Directorate at the Naval Health Research Center (NHRCOID), and the Armed Forces Health Surveillance Branch (AFHSB) all conduct influenza surveillance and perform test-negative case-control analyses to estimate seasonal influenza VE for DoD populations. The mid-season estimates contribute to the aggregate data utilized by the Food and Drug Administration's Vaccine and Related Biological Products Advisory Committee to select the composition of the influenza vaccine for the next influenza season.

Comparison of risedronate versus placebo in preventing anastrozole-induced bone loss in women at high risk of developing breast cancer with osteopenia.

Anastrozole has been shown to prevent breast cancer in postmenopausal women at high risk of the disease, but has been associated with substantial accelerated loss of bone mineral density (BMD) and increased fractures. Here, we investigate the effect of risedronate on BMD after 5 years of follow-up in the IBIS-II prevention trial. 1410 women were enrolled in the bone sub-study and stratified into three strata according to the lowest baseline T-score at spine or femoral neck.

A Highly Effective and Ultra-Long-Acting Anti-Glaucoma Drug, with a Novel Periorbital Delivery Method.

Two features define the future of glaucoma therapeutics: (1) greatly improved ocular hypotensive efficacy and (2) a delivery method that improves patient convenience and compliance. A highly efficacious and extraordinarily long-acting ocular hypotensive agent PGN 9856-isopropyl ester represents a potential next-generation anti-glaucoma drug. A new periorbital drug delivery route was also investigated.

Metastatic bone disease: Pathogenesis and therapeutic options: Up-date on bone metastasis management.

Bone metastases (BM) are a common complication of cancer, whose management often requires a multidisciplinary approach. Despite the recent therapeutic advances, patients with BM may still experience skeletal-related events and symptomatic skeletal events, with detrimental impact on quality of life and survival. A deeper knowledge of the mechanisms underlying the onset of lytic and sclerotic BM has been acquired in the last decades, leading to the development of bone-targeting agents (BTA), mainly represented by anti-resorptive drugs and bone-seeking radiopharmaceuticals.

GnRH-R-Targeted Lytic Peptide Sensitizes Wild-type Ovarian Cancer to PARP Inhibition.

EP-100 is a synthetic lytic peptide that specifically targets the gonadotropin-releasing hormone receptor on cancer cells. To extend the utility of EP-100, we aimed to identify effective combination therapies with EP-100 for ovarian cancer and explore potential mechanisms of this combination. A series of (MTT assay, immunoblot analysis, reverse-phase protein array, comet assay, and immunofluorescence staining) and experiments were carried out to determine the biological effects of EP-100 alone and in combination with standard-of-care drugs.

TOP: Time-to-Event Bayesian Optimal Phase II Trial Design for Cancer Immunotherapy.

Background: Immunotherapies have revolutionized cancer treatment. Unlike chemotherapies, immune agents often take longer to show benefit, and the complex and unique mechanism of action of these agents renders the use of multiple endpoints more appropriate in some trials. These new features of immunotherapy make conventional phase II trial designs, which assume a single binary endpoint that is quickly ascertainable, inefficient and dysfunctional.

Microsatellite instability in endometrial cancer: New purpose for an old test.

Historically, microsatellite instability testing has been used to identify endometrial cancer patients with Lynch Syndrome. Now, it is also being used to identify those who may be immunotherapy candidates.

Olaparib and α-specific PI3K inhibitor alpelisib for patients with epithelial ovarian cancer: a dose-escalation and dose-expansion phase 1b trial.

Background: Based on preclinical work, we found that combination of poly (ADP-ribose) polymerase (PARP) inhibitors with drugs that inhibit the homologous recombination repair (HRR) pathway (such as PI3K inhibitors) might sensitise HRR-proficient epithelial ovarian cancers to PARP inhibitors. We aimed to assess the safety and identify the recommended phase 2 dose of the PARP inhibitor olaparib in combination with the PI3K inhibitor alpelisib in patients with epithelial ovarian cancer and in patients with breast cancer.

Methods: In this multicentre, open-label, phase 1b trial following a 3 + 3 dose-escalation design, we recruited patients aged 18 years or older with the following key eligibility criteria: confirmed diagnosis of either recurrent ovarian, fallopian tube, or primary peritoneal cancer of high-grade serous histology; confirmed diagnosis of either recurrent ovarian, fallopian tube, or primary peritoneal cancer of any histology with known germline BRCA mutations; confirmed diagnosis of recurrent breast cancer of triple-negative histology; or confirmed diagnosis of recurrent breast cancer of any histology with known germline BRCA mutations.

Critical questions in ovarian cancer research and treatment: Report of an American Association for Cancer Research Special Conference.

Substantial progress has been made in understanding ovarian cancer at the molecular and cellular level. Significant improvement in 5-year survival has been achieved through cytoreductive surgery, combination platinum-based chemotherapy, and more effective treatment of recurrent cancer, and there are now more than 280,000 ovarian cancer survivors in the United States. Despite these advances, long-term survival in late-stage disease has improved little over the last 4 decades.

Phase III trials in ovarian cancer: The evolving landscape of front line therapy.

Introduction: Ovarian cancer has a high mortality to case ratio. To improve the initial response to therapy, trials of biologic agents in combination with primary chemotherapy and as maintenance after completing chemotherapy are being conducted. Multiple trials are ongoing and this strategy has great promise.

Heterotypic CAF-tumor spheroids promote early peritoneal metastatis of ovarian cancer.

High-grade serous ovarian cancer (HGSOC) is hallmarked by early onset of peritoneal dissemination, which distinguishes it from low-grade serous ovarian cancer (LGSOC). Here, we describe the aggressive nature of HGSOC ascitic tumor cells (ATCs) characterized by integrin α5 (ITGA5) ATCs, which are prone to forming heterotypic spheroids with fibroblasts. We term these aggregates as metastatic units (MUs) in HGSOC for their advantageous metastatic capacity and active involvement in early peritoneal dissemination.

Endogenous Production of IL1B by Breast Cancer Cells Drives Metastasis and Colonization of the Bone Microenvironment.

Purpose: Breast cancer bone metastases are incurable, highlighting the need for new therapeutic targets. After colonizing bone, breast cancer cells remain dormant, until signals from the microenvironment stimulate outgrowth into overt metastases. Here we show that endogenous production of IL1B by tumor cells drives metastasis and growth in bone.