Annette Hasenburg

Atezolizumab With Bevacizumab and Nonplatinum Chemotherapy for Recurrent Ovarian Cancer: Final Results From the Placebo-Controlled AGO-OVAR 2.29/ENGOT-ov34 Phase III Trial

PURPOSE To evaluate atezolizumab combined with bevacizumab and non–platinum-based chemotherapy for recurrent ovarian cancer. METHODS The double-blind randomized phase III AGO-OVAR 2.29/ENGOT-ov34 trial (ClinicalTrials.gov identifier: NCT03353831 ) enrolled patients with first or second relapse of ovarian cancer ≤6 months after completing platinum-based chemotherapy (or third relapse regardless of treatment-free interval). PD-L1 status was tested centrally (VENTANA SP142 assay) in recent (<3 months) biopsies before random assignment. All patients received bevacizumab and investigator-selected chemotherapy (once weekly paclitaxel or pegylated liposomal doxorubicin) until disease progression or toxicity, plus either atezolizumab 840 mg or placebo once every 2 weeks until progression (maximum 2 years), randomly assigned 1:1, and stratified by number of previous lines, planned chemotherapy, previous bevacizumab, and PD-L1 status. Primary end points were overall survival (OS) and progression-free survival (PFS) in the intention-to-treat population. RESULTS Among 574 patients randomly assigned between September 2018 and July 2022, 72% were bevacizumab-pretreated, 36% had received three previous treatment lines, 26% had PD-L1–positive tumors, and 54% received paclitaxel with study therapy. After 418 patients had died, the hazard ratio for OS was 0.83 (95% CI, 0.68 to 1.01; P = .06; median 14.2 months with atezolizumab and 13.0 months with placebo) and the hazard ratio for PFS was 0.87 (95% CI, 0.73 to 1.04; P = .12; median 6.4 v 6.7 months, respectively). OS hazard ratios were similar regardless of PD-L1 status. Grade ≥3 adverse events occurred in 72% of atezolizumab-treated and 69% of placebo patients. CONCLUSION Combining atezolizumab with bevacizumab and chemotherapy did not significantly improve OS or PFS in patients with recurrent ovarian cancer ineligible for platinum. The safety profile was as expected from previous experience with these drugs.

Patient-Reported Outcome in Metastatic Breast Cancer and Platinum-Resistant Recurrent Ovarian Cancer Patients Treated with Metronomic Cyclophosphamide ± Methotrexate: PROmetronomic

Introduction: Maintenance of subjective well-being and health-related quality of life (HRQoL) play a crucial role in the treatment of metastatic cancer. The metronomic chemotherapy (MCT) may be a favorable treatment option in metastatic breast cancer (MBC) and platinum-resistant recurrent ovarian cancer (ROC). The aim of this study was to evaluate the HRQoL of MBC and ROC patients treated with MCT. Methods: PROmetronomic was a prospective, monocentric study evaluating the HRQoL in MBC and ROC patients treated with oral cyclophosphamide 50 mg daily (+ oral methotrexate 2.5 mg every other day for MBC) from August 2020 to August 2022. The data were obtained using EORTC QLQ-C30, BR23, OV28, and HADS-D via the eHealth-based platform CANKADO. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Results: A total of 5 MBC patients and 9 ROC patients were evaluated. The mean global health status was 47.2 at baseline and 36.1 at the end of MCT (p = 0.350). Functional scales and symptoms remained stable during MCT except for the significant increase of fatigue (51.9 vs. 77.8, p = 0.038). Anxiety and depression were without significant alteration (9.1 and 8.1 at baseline vs. 9.3 and 8.1 after MCT). The median PFS and OS were 10.0 weeks and 28.0 weeks, respectively. No ≥grade 3 toxicities were reported. Conclusion: MCT had no significant impact on HRQoL of our small cohort of heavily pretreated MBC and ROC patients and may represent a valuable treatment option for maintaining HRQoL in selected patients.

Impact of Epidural Anesthesia on the Outcome of Elderly Patients with Endometrial Cancer: Results of a Propensity Score-Matched Analysis

Introduction: Epidural anesthesia is a standard procedure to mitigate pain during surgery for endometrial cancer (EC). Little data exist about the influence of epidural anesthesia on the oncological outcome in elderly patients with EC. This retrospective study aimed to investigate potential correlations between epidural anesthesia and cancer recurrence in patients with EC. Methods: We screened the medical records of patients ≥60 years treated surgically for EC at the University Medical Center Mainz between January 2008 and December 2019. All women underwent general anesthesia (GA) alone or combined with epidural anesthesia (EGA). Cox regression, the Kaplan-Meier method and propensity score matching were used to analyze the prognostic influence of the anesthesiologic regime on survival. Results: A total of 152 women with EC were included. Twenty-nine patients (19.1%) formed the EGA cohort. The median time of follow-up (FU) was 31 months (interquartile range [IQR]: 8–67.5). The EGA cohort showed more in-hospital complications (27.6 vs. 8.9%; p = 0.006), especially thromboembolic events (3 vs. 0 events; p = 0.006), as well as a longer hospital stay (11 [IQR: 8–13] vs. 7 [IQR: 4–9] days; p < 0.001). Twenty-six patients (17.1%) developed a recurrence in the follow-up at a median of 13 months [IQR: 7.75–29.5]. Thirty-two patients died during FU (21.1%). The EGA cohort showed higher FIGO stages and a higher histological grading than the GA cohort. In the Kaplan-Meier analysis, EGA showed a significantly reduced 5-year recurrence-free survival (RFS) (36.5% vs. 72.6%, p < 0.001) and overall survival (OS) (58.6% vs. 79.9%, p = 0.008). However, in multivariate Cox regression analysis including FIGO stages and histological grading, EGA did not influence RFS (HR: 2.02; 95%-CI: [0.99–4.12], p = 0.054), and OS (HR: 1.03; 95%-CI: [0.40–2.66], p = 0.951). This was backed up by the propensity score- matched analysis for survival (RFS: p = 0.604, OS: p = 0.86). Conclusion: Considering risk factors, epidural anesthesia in combination with GA did not differ in recurrence-free and overall survival compared to GA. Prospective randomized trials are warranted in order to further evaluate this topic.

G-8 Geriatric Screening Tool Independently Predicts Progression-Free Survival in Older Ovarian Cancer Patients Irrespective of Maximal Surgical Effort: Results of a Retrospective Cohort Study

Background: We evaluated the prognostic impact of various global health assessment tools in patients older than 60 years with ovarian cancer (OC). Methods: G-8 geriatric screening tool (G-8 score), Lee Schonberg prognostic index, Eastern Cooperative Oncology Group (ECOG) performance status, and Charlson Comorbidity Index (CCI) were determined retrospectively in a consecutive cohort of elderly patients with OC. Univariate and multivariate Cox regression analyses and Kaplan-Meier method were performed to analyze the impact of the preoperative global health status on survival. Results: 116 patients entered the study. In multivariate analysis adjusted for clinical-pathological factors, only the G-8 score retained significance as a prognostic parameter of progression-free survival (PFS) (hazard ratio [HR]: 1.970; 95% confidence interval [CI] [1.056–3.677]; p = 0.033). Fifty-six patients were classified as G-8-nonfrail with an increased PFS compared to 50 G-8-frail patients (53.4% vs. 16.7%; p = 0.010). A higher CCI was associated with decreased PFS (45.1% vs. 22.2%; p = 0.012), but it did not influence the risk of recurrences or death (p = 0.360; p = 0.111). The Lee Schonberg prognostic index, the ECOG, and age were not associated with survival. Conclusions: The G-8 score independently predicted PFS in elderly OC patients regardless of maximal surgical effort. Thus, it could be useful to assess surgical treatment based on frailty rather than age alone.

The effect of fertility-sparing surgery on sexuality and global quality of life in women with malignant ovarian germ cell and sex cord stromal tumors: an analysis of the CORSETT database of the AGO study group

Abstract Purpose Malignant ovarian germ cell (MOGCT) and sex cord stromal tumors (SCST) are ovarian neoplasms that affect disproportionally young women. Little is known about the impact of surgical and adjuvant management of these patient’s sexual life. This study investigated the effect of fertility-sparing surgery on sexual activity and global quality of life (gQoL) in women with MOGCT and SCST. Methods CORSETT was an observational, multicenter, mixed retrospective/prospective cohort study of the AGO study group. Women of any age who had been diagnosed with MOGCTs and SCSTs between 2001 and 2011 were asked to complete the Sexual Activity Questionnaire (SAQ) and the EORTC QLQ-C30. Results In total, 355 patients were included. Of these, 152 patients with confirmed histological diagnosis had completed the questionnaires. A total of 106 patients were diagnosed with SCST and 46 with MOGCT. Totally, 83 women (55%) were sexually active. After fertility-sparing surgery, patients had a 2.6 fold higher probability for being sexually active than after non-fertility-conserving treatment (unadjusted odds ratio (OR) 2.6, p = 0.01). After adjustment for age, time since diagnosis, FIGO stage, histology and phase of disease, the OR dropped to 1.8 (p = 0.22). Of the sexually active patients, 35 (42%) reported high levels of discomfort during intercourse; 38% after fertility-sparing; and 58% after non-fertility-sparing surgery (adjusted OR 2.8, p = 0.18). Women with fertility-conserving treatment reported a significantly better global QoL (Fadj 2.1, 6.2 points difference, p = 0.03) but not more pleasure during intercourse than women without fertility-sparing surgery (Fadj 0.4, p = 0.52). Conclusion Fertility preserving approaches should be offered to every patient, when oncologically acceptable.

Atezolizumab With Bevacizumab and Chemotherapy vs Bevacizumab and Chemotherapy in Early Relapse Ovarian Cancer

This is a phase III, randomized, partially blinded, multicenter trial to evaluate the efficacy and safety of atezolizumab plus bevacizumab and chemotherapy compared to placebo plus bevacizumab and chemotherapy in patients with recurrent ovarian-, fallopian tube, or primary peritoneal cancer with 1st or 2nd relapse within 6 months after platinum based chemotherapy or 3rd relapse.