Leah McNally

Cediranib and Olaparib Combination Compared With Cediranib or Olaparib Alone, or Chemotherapy in Platinum-Resistant or Primary Platinum-Refractory Ovarian Cancer: NRG-GY005

PURPOSE We assessed the efficacy of cediranib, olaparib, and cediranib/olaparib compared with standard-of-care chemotherapy (SOC) in platinum-resistant or platinum-refractory epithelial ovarian cancer (PROC). PATIENTS AND METHODS NRG-GY005 is an open-label, four-arm, phase II/III superiority trial enrolling patients with high-grade serous/endometrioid PROC and one to three previous therapies. Key exclusion criteria included previous receipt of poly(ADP-ribose) polymerase inhibitor or receipt of antiangiogenic therapy in the recurrent setting. Treatment arms (SOC [once weekly paclitaxel, topotecan, or pegylated liposomal doxorubicin], cediranib, olaparib, or cediranib/olaparib) were equally randomized. A preplanned interim futility analysis on the basis of progression-free survival (PFS) selected treatment arms to advance to phase III. PFS and overall survival (OS) were phase III coprimary end points, with hierarchical testing of PFS followed by OS to preserve type 1 error control, designed to have 90% power for a 0.625 PFS hazard ratio (HR). OS was tested after PFS in the multiple hierarchical testing procedure. Secondary end points included objective response rate (ORR) and patient-reported outcomes. RESULTS Five hundred sixty-two eligible patients were enrolled for phase II/III. Three arms met PFS criteria to carry forward to phase III (SOC, cediranib/olaparib, and cediranib). Median PFS was 3.4, 5.2, and 4 months with SOC, cediranib/olaparib, and cediranib, respectively, with a median follow-up duration of 42.2 months. PFS HR estimates for cediranib/olaparib and cediranib ( v SOC) were 0.796 (98.3% CI, 0.597 to 1.060) and 0.972 (98.3% CI, 0.726 to 1.300), respectively. Median OS was 13.6, 12.8, and 10.5 months, and of 443 patients with measurable disease, ORR was 8.6%, 24.7%, and 13.1% for SOC, cediranib/olaparib, and cediranib, respectively. No new safety signals were identified. In patients receiving cediranib/olaparib, no statistically significant difference was observed on the NFOSI-DRS-P subscale compared with SOC (98.3% CI, –1.3 to 1.5, P = .8725). CONCLUSION The cediranib-containing arms demonstrated clinical activity on the basis of PFS but were not superior compared with SOC.

Use of the Frailty “Timed Up and Go” Test to Predict Perioperative Complications in Patients Undergoing Gynecologic Cancer Surgery

To assess the predictive value of frailty measured by the timed up and go (TUG) test on perioperative outcomes versus other perioperative screening methods. Retrospective cohort study SETTING: Duke University Hospital and Duke Raleigh Hospital PATIENTS: Patients who underwent surgery with gynecologic oncologists at our institution from October 2019 to October 2023 with a preoperative TUG time recorded were included. TUG times were recorded preoperatively. TUG time >12 seconds was considered frail. American Society of Anesthesiologists scores were extracted from the medical record. Modified frailty index (mFI) was calculated using 11 variables extracted from the medical record. Outcomes included postoperative complications, length of stay, and postoperative disposition. Comparisons between TUG times dichotomized at 8 and 12 seconds were made using Wilcoxon rank sum or chi-square; logistic regression was used to predict TUG time using these dichotomizations. Overall, 174 patients were included; 39 (22.4%) underwent laparotomy, 123 (70.6%) underwent laparoscopy, and 12 (6.9%) underwent other minor surgeries. Frail patients (TUG time > 12 seconds) were older and had higher mFI scores and lower preoperative albumin than nonfrail patients. There were no differences in major or minor complication rates after laparoscopic surgery between frail and nonfrail patients. American Society of Anesthesiologists and mFI were not associated with the need for transfusion (p > .05). Frail patients were more likely to receive a perioperative blood transfusion compared to nonfrail patients in the overall cohort (19.2% vs 4.1%, p = .0034). TUG time did not predict length of stay or postoperative disposition. Slower TUG times were associated with comorbidities, older age, and malnutrition. Frailty was not associated with complications in those who underwent laparoscopic surgery. Our findings support the use of this easy-to-administer practical frailty screening tool compared to more traditional methods.

Testing the Combination of Cediranib and Olaparib in Comparison to Each Drug Alone or Other Chemotherapy in Recurrent Platinum-Resistant Ovarian Cancer

This randomized phase II/III trial studies how well cediranib maleate and olaparib work when given together or separately, and compares them to standard chemotherapy in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that has returned (recurrent) after receiving chemotherapy with drugs that contain platinum (platinum-resistant) or continued to grow while being treated with platinum-based chemotherapy drugs (platinum-refractory). Cediranib maleate and olaparib may stop the growth of tumor cells by blocking enzymes needed for cell growth. Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving cediranib maleate and olaparib together may cause more damage to cancer cells when compared to either drug alone or standard chemotherapy.