Browsing by Subject "female"

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    Translational randomized phase II trial of cabozantinib in combination with nivolumab in advanced, recurrent, or metastatic endometrial cancer
    (BMJ, 2022-03) Lheureux, Stephanie; Matei, Daniela E.; Konstantinopoulos, Panagiotis A.; Wang, Ben X.; Gadalla, Ramy; Block, Matthew S.; Jewell, Andrea; Gaillard, Stephanie L.; McHale, Michael; McCourt, Carolyn; Temkin, Sarah; Girda, Eugenia; Backes, Floor J.; Werner, Theresa L.; Duska, Linda; Kehoe, Siobhan; Colombo, Ilaria; Wang, Lisa; Li, Xuan; Wildman, Rachel; Soleimani, Shirin; Lien, Scott; Wright, John; Pugh, Trevor; Ohashi, Pamela S.; Brooks, David G.; Fleming, Gini F.; Obstetrics and Gynecology, School of Medicine
    Background Combining immunotherapy and antiangiogenic agents is a promising treatment strategy in endometrial cancer. To date, no biomarkers for response have been identified and data on post-immunotherapy progression are lacking. We explored the combination of a checkpoint inhibitor (nivolumab) and an antiangiogenic agent (cabozantinib) in immunotherapy-naïve endometrial cancer and in patients whose disease progressed on previous immunotherapy with baseline biopsy for immune profiling. Patients and methods In this phase II trial (ClinicalTrials.gov NCT03367741, registered December 11, 2017), women with recurrent endometrial cancer were randomized 2:1 to nivolumab with cabozantinib (Arm A) or nivolumab alone (Arm B). The primary endpoint was Response Evaluation Criteria in Solid Tumors-defined progression-free survival (PFS). Patients with carcinosarcoma or prior immune checkpoint inhibitor received combination treatment (Arm C). Baseline biopsy and serial peripheral blood mononuclear cell (PBMC) samples were analyzed and associations between patient outcome and immune data from cytometry by time of flight (CyTOF) and PBMCs were explored. Results Median PFS was 5.3 (90% CI 3.5 to 9.2) months in Arm A (n=36) and 1.9 (90% CI 1.6 to 3.4) months in Arm B (n=18) (HR=0.59, 90% CI 0.35 to 0.98; log-rank p=0.09, meeting the prespecified statistical significance criteria). The most common treatment-related adverse events in Arm A were diarrhea (50%) and elevated liver enzymes (aspartate aminotransferase 47%, alanine aminotransferase 42%). In-depth baseline CyTOF analysis across treatment arms (n=40) identified 35 immune-cell subsets. Among immunotherapy-pretreated patients in Arm C, non-progressors had significantly higher proportions of activated tissue-resident (CD103+CD69+) ɣδ T cells than progressors (adjusted p=0.009). Conclusions Adding cabozantinib to nivolumab significantly improved outcomes in heavily pretreated endometrial cancer. A subgroup of immunotherapy-pretreated patients identified by baseline immune profile and potentially benefiting from combination with antiangiogenics requires further investigation.
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    Validating the Postdischarge Surgical Recovery Scale 13 as a Measure of Perceived Postoperative Recovery After Laparoscopic Sacrocolpopexy
    (Wolters Kluwer, 2017-03) Carpenter, Janet S.; Heit, Michael; Chen, Chen X.; Stewart, Ryan; Hamner, Jennifer; Rand, Kevin L.; School of Nursing
    Objectives No postoperative recovery measurement tools have been validated among women undergoing laparoscopic sacrocolpopexy for pelvic organ prolapse, which impedes development and testing of strategies to improve recovery. The purpose of this study was to evaluate the performance of the Postdischarge Surgical Recovery Scale (PSR) as a measure of perceived recovery in laparoscopic sacrocolpopexy patients. Methods Women (N = 120) with stage 2 or higher pelvic organ prolapse undergoing laparoscopic sacrocolpopexy completed a 15-minute postoperative survey (days 7, 14, 42, and 90 [each ± 3 days]) which included the 15-item PSR. A confirmatory factor analysis was conducted using data from 14 days postsurgery, when patients would have begun to recover, but there was likely to be substantial variability in recovery across patients. We also assessed validity and explored sensitivity to change over time and minimally important difference values. Results Confirmatory factor analysis indicated a good fitting model for a reduced version of the PSR (ie, PSR13). Regressions showed that the PSR13 prospectively predicted single-item recovery scores. The PSR13 recovery significantly improved from days 7 to 42, suggesting the PSR13 is sensitive to change. Descriptive statistics including minimally important differences are reported. The minimally important difference was estimated to be around 5 points. Conclusions The PSR13 is a psychometrically sound tool for measuring recovery over time in this population. Its short length makes it an ideal postoperative recovery measure in clinical practice or research.