How to optimize and evaluate diversity in gynecologic cancer clinical trials: statements from the GCIG Barcelona Meeting.

Findings from clinical trials have led to advancement of care for patients with gynecologic malignancies. However, restrictive inclusion of patients into trials has been widely criticized for inadequate representation of the real-world population. Ideally, patients enrolled in clinical trials should represent a broader population to enhance external validity and facilitate translation of outcomes across all relevant groups.

Real-world outcomes associated with bevacizumab combined with chemotherapy in platinum-resistant ovarian Cancer.

Objectives: The addition of bevacizumab to chemotherapy for platinum-resistant (PL-R) ovarian cancer (OC) improved progression-free (PFS) but not overall survival (OS) in clinical trials. We explored real-world outcomes in Ontario, Canada, and compared survival in the pre- and post-bevacizumab era.

Methods: Administrative databases were utilized to identify all patients treated with bevacizumab for PL-R OC.

Real-world outcomes associated with use of front-line bevacizumab in ovarian cancer.

Background: In the pivotal ICON7 study, addition of bevacizumab to front-line treatment of ovarian cancer (OC) significantly improved overall survival (OS) (p = 0.03) in a high-risk subgroup of patients with suboptimally debulked/unresectable stage III or IV disease, leading to approval in Ontario, Canada in March 2016. Here we describe utilization of bevacizumab for front-line, high-risk OC and determine outcomes in routine clinical practice.

CA-125 Early Dynamics to Predict Overall Survival in Women with Newly Diagnosed Advanced Ovarian Cancer Based on Meta-Analysis Data.

(1) Background: Cancer antigen 125 (CA-125) is a protein produced by ovarian cancer cells that is used for patients' monitoring. However, the best ways to analyze its decline and prognostic role are poorly quantified. (2) Methods: We leveraged individual patient data from the Gynecologic Cancer Intergroup (GCIG) meta-analysis (N = 5573) to compare different approaches summarizing the early trajectory of CA-125 before the prediction time (called the landmark time) at 3 or 6 months after treatment initiation in order to predict overall survival.

Clinical outcome and biomarker assessments of a multi-centre phase II trial assessing niraparib with or without dostarlimab in recurrent endometrial carcinoma.

This multi-centre, non-randomized, open-label, phase II trial (NCT03016338), assessed niraparib monotherapy (cohort 1, C1), or niraparib and dostarlimab (cohort 2, C2) in patients with recurrent serous or endometrioid endometrial carcinoma. The primary endpoint was clinical benefit rate (CBR), with ≥5/22 overall considered of interest. Secondary outcomes were safety, objective response rate (ORR), duration of response, progression free survival and overall survival.

State of the Biomarker Science in Ovarian Cancer: A National Cancer Institute Clinical Trials Planning Meeting Report.

Purpose: Despite therapeutic advances in the treatment of ovarian cancer (OC), 5-year survival remains low, and patients eventually die from recurrent, chemotherapy-resistant disease. The National Cancer Gynecologic Cancer Steering Committee identified the integration of scientifically defined subgroups as a top strategic priority in clinical trial planning.

Methods: A group of experts was convened to review the scientific literature in OC to identify validated predictive biomarkers that could inform patient selection and treatment stratification.

Neoadjuvant and Adjuvant Systemic Therapy for Newly Diagnosed Stage II-IV Epithelial Ovary, Fallopian Tube, or Primary Peritoneal Carcinoma: A Practice Guideline.

Background: This study aims to provide guidance for the use of neoadjuvant and adjuvant systemic therapy in women with newly diagnosed stage II-IV epithelial ovary, fallopian tube, or primary peritoneal carcinoma.

Methods: EMBASE, MEDLINE, and Cochrane Library were investigated for relevant systematic reviews and phase III trials. Articles focusing on consolidation and maintenance therapies were excluded.

The needs of gynecological cancer survivors at the end of primary treatment: A scoping review and proposed model to guide clinical discussions.

Objective: Gynecological cancer (GC) survivors have unmet needs when they complete primary cancer treatment. Despite this, no known research has summarized these needs and survivors' suggestions to address them. We conducted a scoping review to fill these gaps and develop a model useful to guide clinical discussions and/or interventions.

Practice Patterns and Outcomes of Novel Targeted Agents for the Treatment of ERBB2-Positive Metastatic Breast Cancer.

Importance: Clinical trials have shown that the addition of pertuzumab to trastuzumab-based chemotherapy for first-line treatment of ERBB2-positive metastatic breast cancer is associated with considerable improvement in overall survival (OS). In the second-line setting, trastuzumab emtansine (T-DM1) improves OS compared with capecitabine/lapatinib in patients previously treated with trastuzumab-based chemotherapy. However, there are few data describing long-term real-world outcomes with these agents.

Neoadjuvant and adjuvant systemic therapy for newly diagnosed stage II- IV epithelial ovary, fallopian tube, or primary peritoneal carcinoma: A systematic review.

Background: To systematically review neoadjuvant and adjuvant therapy options for women with newly diagnosed stage II-IV ovarian cancer.

Methods: Phase III trials were searched using MEDLINE, EMBASE, and Cochrane Library. Maintenance therapies were excluded.

Influence of the competing risk of death on estimates of disease recurrence in trials of adjuvant endocrine therapy for early-stage breast cancer: A secondary analysis of MA.27, MA.17 and MA.17R.

Background: Many women diagnosed with early-stage hormone-sensitive breast cancer die of causes other than their breast cancer. These competing risks can create challenges in analysing and clearly communicating data on risk of breast cancer recurrence or death. Here, we quantify the impact of competing risks on estimates of disease recurrence and benefit from therapy.

The Voices of Young Women with Breast Cancer: Providing Support and Information for Improved Fertility Preservation Discussions.

Fertility is a concern for young women with breast cancer. We explore patient experiences with fertility discussions at diagnosis to identify barriers and preferences to patient-centered delivery of care. A qualitative study was conducted on consecutive, female breast cancer survivors, 39 years of age or younger at diagnosis and within 2 years of diagnosis, who attended routine outpatient follow-up at a large academic teaching center.

The role of niraparib for the treatment of ovarian cancer.

Epithelial ovarian cancer (EOC) remains a leading cause of cancer death in women. Approximately 10-15% of patients with EOC harbor a genetic predisposition due to mutations in BRCA1/2 genes. In the recurrent setting, prolonging time to platinum-resistance may improve progression-free survival.

Perceived Barriers to Goals of Care Discussions With Patients With Advanced Cancer and Their Families in the Ambulatory Setting: A Multicenter Survey of Oncologists.

Background: Earlier goals of care (GOC) discussions in patients with advanced cancer are associated with less aggressive end-of-life care including decreased use of medical technologies. Unfortunately, conversations often occur late in the disease trajectory when patients are acutely unwell. Here, we evaluate practitioner perspectives of patient, family, physician, and external barriers to early GOC discussions in the ambulatory oncology setting.

Is hormonal therapy effective in advanced endometrial cancer? A systematic review and meta-analysis.

Background: Hormonal therapy (HT) is used commonly in the treatment of advanced endometrial cancer (EC). However, a 2010 Cochrane Review did not show a survival benefit for HT. Here, we quantify its effects and explore the influence of clinico-pathologic factors and hormone receptor (HR) status on overall response rates (ORR).

Capecitabine in early breast cancer: A meta-analysis of randomised controlled trials.

Purpose: Capecitabine is an effective therapy for metastatic breast cancer. Its role in early breast cancer is uncertain due to conflicting data from randomised controlled trials (RCTs).

Methods: PubMed and major conference proceedings were searched to identify RCTs comparing standard chemotherapy with or without capecitabine in the neoadjuvant or adjuvant setting.

Bone Modifier Use as Adjuvant Therapy for Early Breast Cancer.

Purpose Of Review: Many studies have examined the effects of adjuvant bisphosphonates on long-term breast cancer outcomes. However, results have been inconsistent. Here, we review the evidence for their role in early breast cancer.

Is the neutrophil-to-lymphocyte ratio prognostic of survival outcomes in gynecologic cancers? A systematic review and meta-analysis.

Background: Presence of a high neutrophil-to-lymphocyte ratio (NLR) has been associated with increased mortality in several malignancies. Here, we quantify the effect of NLR on survival in patients with gynecologic cancers, and examine the effect of clinico-pathologic factors on its prognostic value.

Methods: A systematic search of electronic databases was conducted to identify publications exploring the association of pre-treatment blood NLR with overall survival (OS) and event-free survival (EFS) among patients with ovarian, endometrial and cervical cancers.

Cardiovascular toxicity of angiogenesis inhibitors in treatment of malignancy: A systematic review and meta-analysis.

Background: The cardiovascular risk of angiogenesis inhibitors is not well-quantified. We hypothesized that, compared to direct vascular endothelial growth factor (VEGF) inhibitors (anti-VEGF antibodies or decoy receptors), small molecule agents have higher risk due to their less specific mechanism.

Methods: We searched the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials for phase III randomised controlled trials comparing angiogenesis inhibitor-based therapy to other systemic therapy.

Prognostic role of neutrophil-to-lymphocyte ratio in breast cancer: a systematic review and meta-analysis.

Background: The presence of a high neutrophil-to-lymphocyte ratio (NLR) has been associated with increased mortality in several malignancies. Here, we quantify the effect of NLR on survival in patients with breast cancer, and examine the effect of clinicopathologic factors on its prognostic value.

Methods: A systematic search of electronic databases was conducted to identify publications exploring the association of blood NLR (measured pre treatment) and overall survival (OS) and disease-free survival (DFS) among patients with breast cancer.

The Role of the 21-Gene Recurrence Score in Breast Cancer Treatment.

Several multi-gene assays have been developed to predict the risk of recurrence in patients with estrogen receptor-positive early breast cancer and in whom endocrine therapy is planned. The 21-gene assay is widely used and its prognostic value has been retrospectively validated, showing significant differences in the risk of distant recurrence for patients at high versus low risk. Its role in predicting chemotherapy benefit has also been established, showing a clear benefit for high-risk patients and minimal benefit in those at low risk.

Influence of companion diagnostics on efficacy and safety of targeted anti-cancer drugs: systematic review and meta-analyses.

Background: Companion diagnostics aim to identify patients that will respond to targeted therapies, therefore increasing the clinical efficacy of such drugs. Less is known about their influence on safety and tolerability of targeted anti-cancer agents.

Methods And Findings: Randomized trials evaluating targeted agents for solid tumors approved by the US Food and Drug Administration since year 2000 were assessed.

Cardiovascular toxicity of multi-tyrosine kinase inhibitors in advanced solid tumors: a population-based observational study.

Background: Treatment with small molecule tyrosine kinase inhibitors (TKIs) has improved survival in many cancers, yet has been associated with an increased risk of adverse events. Warnings of cardiovascular events are common in drug labels of many TKIs. Despite these warnings, cardiovascular toxicity of patients treated with TKIs remains unclear.

Author financial conflicts of interest, industry funding, and clinical practice guidelines for anticancer drugs.

Purpose: Clinical practice guidelines (CPGs) and consensus statements (CSs) are used to apply evidence-based medicine or expert recommendations to clinical practice. Here we explore author financial conflicts of interest (FCOIs), sources of guideline funding, and their relationship with endorsement of specific drugs.

Methods: An electronic search of MEDLINE was conducted to identify CPGs and CSs for common solid cancers published between January 2003 and October 2013.