Nivolumab for mismatch-repair-deficient or hypermutated gynecologic cancers: a phase 2 trial with biomarker analyses.

Programmed death-1 (PD-1) inhibitors are approved for therapy of gynecologic cancers with DNA mismatch repair deficiency (dMMR), although predictors of response remain elusive. We conducted a single-arm phase 2 study of nivolumab in 35 patients with dMMR uterine or ovarian cancers. Co-primary endpoints included objective response rate (ORR) and progression-free survival at 24 weeks (PFS24).

Carboplatin dosing in the treatment of ovarian cancer: An NRG oncology group study.

Objective: To determine the effects of using National Comprehensive Cancer Network (NCCN) guidelines to estimate renal function on carboplatin dosing and explore adverse effects associated with a more accurate estimation of lower creatinine clearance (CrCl).

Methods: Retrospective data were obtained for 3830 of 4312 patients treated on GOG182 (NCT00011986)-a phase III trial of platinum-based chemotherapy for advanced-stage ovarian cancer. Carboplatin dose per patient on GOG182 was determined using the Jelliffe formula.

The effect of older age on treatment outcomes in women with advanced ovarian cancer receiving chemotherapy: An NRG-Oncology/Gynecologic Oncology Group (GOG-0182-ICON5) ancillary study.

Objective: To assess the effect of age on overall survival (OS) in women with ovarian cancer receiving chemotherapy. Secondary objectives were to describe the effect of age on treatment compliance, toxicities, progression free survival (PFS), time from surgery to chemotherapy, and rates of optimal cytoreduction.

Methods: Women enrolled in GOG 0182-ICON5 with stage III or IV epithelial ovarian cancer (EOC) who underwent surgery and chemotherapy between 2001 and 2004 were included.

Missed Opportunities in Geriatric Oncology Research.

The field of geriatric oncology has made significant progress in recent decades, but there are still missed opportunities in important areas of research. One issue is the underrepresentation of older patients, especially those aged 75 years and older, in clinical trials. This has resulted in a lack of high-quality data for the care of this population, and the American Society of Clinical Oncology has called for an increase in the evidence base for older patients with cancer.

Feasibility of a Geriatric Oncology Longitudinal End to End (GOLDEN) Program in a Tertiary Cancer Center in Singapore.

Introduction: In the National University Cancer Institute, Singapore (NCIS), 2 pilot programs providing (i) surgical prehabilitation before cancer surgery and (ii) geriatric oncology support for older adults planned for chemotherapy and/or radiotherapy were merged to form the Geriatric Oncology Longitudinal End to eNd (GOLDEN) program in 2019 to support patients from the time of their cancer diagnosis, through their treatment process, to cancer survivorship.

Methods And Materials: Older adults aged ≥65 years were enrolled in either surgical prehabilitation, the geriatric medical oncology (GO) arm, or both. All patients undergo a geriatric assessment.

Durvalumab with or without tremelimumab in patients with persistent or recurrent endometrial cancer or endometrial carcinosarcoma: A randomized open-label phase 2 study.

Introduction: Our understanding of the biologic heterogeneity of endometrial cancer has improved, but which patients benefit from single-agent versus combination immune checkpoint blockade remains unclear.

Methods: We conducted a single-center, randomized, open-label, phase 2 study of durvalumab 1500 mg (Arm 1) versus durvalumab 1500 mg plus tremelimumab 75 mg every 4 weeks (Arm 2) in patients with endometrial carcinoma. The primary endpoints were overall response rate (ORR) and progression-free survival (PFS) at 24 weeks.

Improving Cancer Care for Patients With CKD: The Need for Changes in Clinical Trials.

Chemotherapeutic agents used to treat cancer generally have narrow therapeutic indices along with potentially serious adverse toxicities. Many cancer drugs are at least partially excreted through the kidney and, thus, the availability of accurate data on safe and effective dosing of these drugs in patients with chronic kidney disease (CKD) is essential to guide treatment decisions. Typically, during drug development, initial clinical studies only include patients with normal or only mildly impaired kidney function.

Chemotherapy and gene expression profiling in older early luminal breast cancer patients: An International Society of Geriatric Oncology systematic review.

Background: The benefit of chemotherapy for older patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer (EBC) is a key area of debate. Gene expression profiling (GEP) may identify patients deriving benefit, but their predictive role has not been established for older adults. We summarise evidence on efficacy, safety, and quality-of-life impacts of chemotherapy and on GEP use and impact in older HR-positive, HER2-negative EBC patients.

Metastatic Colorectal Cancer Outcomes by Age Among ARCAD First- and Second-Line Clinical Trials.

Background: We evaluated the time to progression (TTP) and survival outcomes of second-line therapy for metastatic colorectal cancer among adults aged 70 years and older compared with younger adults following progression on first-line clinical trials.

Methods: Associations between clinical and disease characteristics, time to initial progression, and rate of receipt of second-line therapy were evaluated. TTP and overall survival (OS) were compared between older and younger adults in first- and second-line trials by Cox regression, adjusting for age, sex, Eastern Cooperative Oncology Group Performance Status, number of metastatic sites and presence of metastasis in the lung, liver, or peritoneum.

Clinical Trial Endpoints in Metastatic Cancer: Using Individual Participant Data to Inform Future Trials Methodology.

Meta-analysis based on individual participant data (IPD) is a powerful methodology for synthesizing evidence by combining information drawn from multiple trials. Hitherto, its principal application has been in questions of clinical management, but an increasingly important use is in clarifying trials methodology, for instance in the selection of endpoints, as discussed in this review. In oncology, the Aide et Recherche en Cancérologie Digestive (ARCAD) Metastatic Colorectal Cancer Database is a leader in the use of IPD-based meta-analysis in methodological research.

Phase II study of enzalutamide in androgen receptor positive, recurrent, high- and low-grade serous ovarian cancer.

Objectives: We sought to determine the safety and efficacy of the oral androgen receptor antagonist enzalutamide in patients with previously treated, recurrent, AR-positive (AR+) ovarian cancer.

Methods: This was a single-institution phase II study of patients with AR+ ovarian cancer with measurable disease with 1-3 prior lines of chemotherapy; patients were screened for enrollment from 11/2013-7/2018. Following consent, archival tissue was evaluated for AR+.

The association of age with acute toxicities in NRG oncology combined modality lower GI cancer trials.

Purpose: Expected toxicity from chemoradiation (CRT) is an important factor in treatment decisions but is poorly understood in older adults with lower gastrointestinal (GI) malignancies. Our objective was to compare acute adverse events (AAEs) of older and younger adults with lower GI malignancies treated on NRG studies.

Methods: Data from 6 NRG trials, testing combined modality therapy in patients with anal or rectal cancer, were used to test the hypothesis that older age was associated with increased AAEs.

Targeted Agents for HER2-Positive Breast Cancer: Optimal Use in Older Patients.

The human epidermal growth factor-2 (HER2) gene is overexpressed in 15-20 % of all breast cancers. HER2 overexpression is a predictive factor in breast cancer and is associated with high rates of disease recurrence and death in the absence of adjuvant systemic therapy. With the advent of HER2-directed therapies, there has been a significant improvement in the outcome of HER2-positive (HER2+) breast cancer in all clinical settings.

Disparities in older adult accrual to cancer trials: Analysis from the alliance for clinical trials in oncology (A151736).

Background: Older adults are under-represented in cancer clinical trials. However, it remains unclear which types of trials under-enroll aging patients. We aimed to identify associations between trial characteristics and disparate enrollment of older adults onto trials sponsored by the Alliance for Clinical Trials in Oncology (Alliance).

Secondary Cytoreduction and Carboplatin Hyperthermic Intraperitoneal Chemotherapy for Platinum-Sensitive Recurrent Ovarian Cancer: An MSK Team Ovary Phase II Study.

Purpose: The purpose of this phase II study was to evaluate hyperthermic intraperitoneal chemotherapy (HIPEC) with carboplatin for recurrent ovarian cancer during secondary cytoreductive surgery.

Materials And Methods: Patients were intraoperatively randomly assigned to carboplatin HIPEC (800 mg/m for 90 minutes) or no HIPEC, followed by five or six cycles of postoperative IV carboplatin-based chemotherapy, respectively. Based on a binomial single-stage pick-the-winner design, an arm was considered winner if ≥ 17 of 49 patients were without disease progression at 24 months post-surgery.

Predictors of Unplanned Hospitalizations Among Older Adults Receiving Cancer Chemotherapy.

Purpose: Hospitalizations during cancer treatment are costly, can impair quality of life, and negatively affect therapy completion. Our objective was to identify risk factors for unplanned hospitalization among older adults receiving chemotherapy.

Methods: This is a secondary analysis of a multisite cohort study (N = 750) of patients ≥ 65 years of age evaluated with a geriatric assessment (GA) to predict chemotherapy toxicity.