e18032 Background: PRO enable direct measurement of the experiences of patients with cancer. Anti-programmed death 1 (PD-1) therapies have shown favorable PRO in lung cancer but a data gap remains in EC. Dostarlimab is an investigational anti-PD-1 monoclonal antibody which has shown promising activity in GARNET in advanced mismatch repair deficient (dMMR) EC pts (with an ORR of 42.9% and a disease control rate of 58.6%), and a low incidence of symptomatic grade ≥3 treatment-related adverse events (anemia [2·9%], colitis [1·9%], and diarrhea [1·9%]). Here, we report on PRO measures collected from pts with dMMR/microsattelite instability high (MSI-H) EC in the single-arm GARNET trial. Methods: Pts with dMMR/MSI-H EC confirmed by local tests, with recurrent or advanced disease that progressed on a platinum regimen were enrolled. Pts received 500 mg Q3W of dostarlimab for 4 cycles, then 1000 mg Q6W until disease progression or discontinuation. PRO assessment was an exploratory endpoint and was measured by the EORTC Quality of Life Questionnaire (QLQ-C30), a validated instrument used to evaluate quality of life, functioning, disease symptoms, and treatment-related side effects. PRO were collected at each dose administration, end of treatment, and follow-up. A mixed-model for repeated measures was used to assess change from baseline, accounting for time and baseline ECOG scores. The threshold to determine clinically meaningful group-level change was ±10 points. Results: PRO data were available for 43 pts. Compliance rates were high at 98%. Relative to baseline, pts reported meaningful improvements in pain, insomnia, and social and emotional functioning over the trial duration. Appetite, nausea, vomiting, constipation, diarrhea, and physical and role functioning were stable over the trial duration. Quality of life and global health status were also maintained. Conclusions: PRO from 43 pts enrolled in the GARNET trial show that disease- and treatment-related symptoms and quality of life are improved or maintained while receiving treatment. These data, along with with the efficacy and safety profile of dostarlimab, strongly support the use of dostarlimab in dMMR/MSI-H advanced EC. Clinical trial information: NCT02715284.
5582 Background: Uterine carcinosarcoma (UCS) is subtype of endometrial cancer (EC) with aggressive behavior and poor prognosis. UCS has not traditionally been included in EC clinical trials and treatment options are limited. Immune-oncology (IO) therapy has shown promise UCS, but it is unknown which patients benefit most. We sought to identify immunogenic markers in UCS and explore treatment response to IO therapy. Methods: Tumor samples were analyzed using Nex-Gen sequencing of the DNA (NextSeq, 592 genes or NovaSeq, whole exome sequencing) and RNA (NovaSeq, whole transcriptome sequencing) and immunohistochemistry (IHC) (Caris Life Sciences, Phoenix, AZ).PD-L1 IHC used SP-142 (cut-off >1%). MSI was tested by FA, IHC and NGS. TMB was measured by totaling somatic mutations per tumor (high > 10 mutations per MB). Immune cell fraction was calculated by QuantiSeq. Overall survival (OS) information was obtained from insurance claims data and Kaplan-Meier estimates were calculated for molecularly defined patient cohorts. Statistical significance was determined using chi-square and Wilcoxon rank sum test and p values adjusted for multiple comparisons (q) to be <0.05. Results: A total of 1,144 UCS tumors underwent comprehensive tumor profiling. 68.4% of samples were obtained from primary tumors and 31.6% from metastatic sites. 21.6% of tumors expressed PD-L1, 8.5% were TMB-H and 6.8% were MSI-H/MMRd. UCS patients treated with IO had longer median overall survival than those not treated with IO (months: 31.2 vs 19.4; HR(95% CI): 0.39 (0.17-0.76) p=0.005). Median OS was also increased for dMMR/MSI-H (OS not yet reached vs 18.9 months); HR(95% CI): 0.56 (0.36-0.92) p=0.019) and TMB-H (OS not yet reached vs 18.9 months); HR(95% CI): 0.62 (0.38-0.99) p=0.047). More patients are needed to determine if these markers predict response to IO therapy. The most common mutations in UCS led to pathway dysregulation in the PI3K, RAS, chromatin remodeling, HR, and WNT pathways. dMMR/MSI-H tumors have distinct molecular profiles compared to MSS tumors (table). Additionally, dMMR/MSI-H tumors had higher TMB (96.9% vs 2.2%, q<0.01) and increased frequency of PDL-1 (23.6% vs 13.8%; q=0.04). Immune checkpoint genes were more often expressed in MSI-H tumors, though this was non-significant except for IFNG (4.66-fold increase; q=0.01). Conclusions: IO therapy is associated with improved survival in USC. MSI and TMB are markers of improved OS in patients with UCS. MSI tumors have a distinct molecular profile compared to MSS tumors, and they appear to be more immunogenic, which could contribute to the improved survival seen in patients who received IO therapy.[Table: see text]
Stromal tumors of the ovary represent approximately 3% of ovarian neoplasms and up to 10% of all ovarian malignancies. This encompasses a diverse group of malignancies that vary in clinical presentation, natural history, prognosis, and recommended treatment. This chapter discusses the details of these rare tumors, provides a general treatment schema for such tumors, reviews details of pathological features, and provides a detailed discussion of surgical and nonsurgical treatment recommendations for patients with each specific tumor type. In addition, the issue of conservative management for preservation of fertility is discussed, and new information regarding genomics is presented.
Objective The goals of this study were to describe opioid and benzodiazepine prescribing practices in the gynecologic oncology patient population and determine risks for opioid misuse in these patients. Methods Retrospective study of opioid and benzodiazepine prescriptions for patients treated for cervical, ovarian (including fallopian tube/primary peritoneal), and uterine cancers within a single healthcare system from January 2016 to August 2018. Results A total of 7643 prescriptions for opioids and/or benzodiazepines were dispensed to 3252 patients over 5754 prescribing encounters for cervical (n=2602, 34.1%), ovarian (n=2468, 32.3%), and uterine (n=2572, 33.7%) cancer. Prescriptions were most often written in an outpatient setting (51.0%) compared with inpatient discharge (25.8%). Cervical cancer patients were more likely to have received a prescription in an emergency department or from a pain/palliative care specialist (p=0.0001). Cervical cancer patients were least likely to have prescriptions associated with surgery (6.1%) compared with ovarian cancer (15.1%) or uterine cancer (22.9%) patients. The morphine milligram equivalents prescribed were higher for patients with cervical cancer (62.6) compared with patients with ovarian and uterine cancer (46.0 and 45.7, respectively) (p=0.0001). Risk factors for opioid misuse were present in 25% of patients studied; cervical cancer patients were more likely to have at least one risk factor present during a prescribing encounter (p=0.0001). Cervical cancer was associated with a higher number of risk factors (p<0.001). Conclusions Opioid and benzodiazepine prescribing patterns differ for cervical, ovarian, and uterine cancer patients. Gynecologic oncology patients are overall at low risk for opioid misuse; however, patients with cervical cancer are more likely to have risk factors present for opioid misuse.
Background We conducted a study to assess the feasibility of two comparable dietary interventions in ovarian cancer survivors (OCS). Methods In a parallel‐group trial, 51 women (mean 53 yrs) stage II–IV OCS were randomly assigned to a plant‐based (PB) diet or a modified NCI diet supplemented with a soy‐based beverage and encapsulated fruit & vegetable juice concentrates (FVJCs). Changes in clinical measures, serum carotenoid & tocopherol levels, dietary intake, anthropometry, and quality of life (HRQOL) were assessed with paired t‐tests. Results At baseline, 28% & 45% of women met guidelines for intake of fiber & fruits and vegetables, respectively. After 6 mo, total serum carotenoid levels and α‐ & β‐carotene were significantly increased in both groups ( P < 0.01); β‐carotene was increased more in the FVJC group. Serum β‐cryptoxanthin levels, fiber intake (+5.2 g/day), servings of juice (+0.9 servings/day) & vegetables (+1.3 servings/day) were all significantly increased in the PB group (all P < 0.05). Serum levels of albumin, lutein & zeaxanthin, retinol, and retinyl palmitate were significantly increased in the FVJC group (all P < 0.05). No changes in CA‐125, anthropometry, or HRQOL were observed. Conclusion This study supports the feasibility of designing dietary interventions for OCS and provides preliminary evidence that encapsulated FVJCs provide comparable amounts of nutrients as the PB diet in OCS.
