Mariam AlHilli

Comparing Durvalumab, Olaparib, and Cediranib Monotherapy, Combination Therapy, or Chemotherapy in Patients with Platinum-Resistant Ovarian Cancer with Prior Bevacizumab: The Phase II NRG-GY023 Trial

Abstract Purpose: We assessed the efficacy of anti–PD-L1 durvalumab in combination with olaparib and cediranib (DOC), compared with the standard-of-care chemotherapy (SOC) in patients with platinum-resistant ovarian cancer (PROC), who had prior bevacizumab. Patients and Methods: NRG-GY023 was the first randomized four-arm superiority phase II trial enrolling patients with high-grade serous/endometrioid or clear-cell PROC with prior bevacizumab exposure. Patients were randomized 1:2:2:2 to SOC (weekly paclitaxel, topotecan, or pegylated liposomal doxorubicin), DOC, durvalumab + cediranib (DC), or olaparib + cediranib (OC). The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival, overall response rate, and safety. The design had 80% power to detect an HR of 0.5 using a one-sided, α = 0.1-level test for each comparison with the SOC with a preplanned interim analysis. Experimental arms with HR estimates (vs. SOC) >0.87 could be discontinued. Results: A total of 153 patients were enrolled between April 4, 2021, and February 1, 2023. Accrual was permanently closed on February 1, 2023, due to futility. With a data cutoff of September 9, 2024, the median PFS was 3.4, 2.9, 2.5, and 2.8 months, and median overall survival was 7.5, 8.3, 5.7, and 10.2 months for SOC, DOC, DC, and OC, respectively. The overall response rate was 4.3% [95% confidence interval (CI), 0.00–0.19], 15.9% (95% CI, 0.07–0.29), 11.9% (95% CI, 0.05–0.24), and 9.1% (95% CI, 0.03–0.20) for SOC, DOC, DC, and OC, respectively. Compared with SOC, the PFS HR estimates were 1.003 (95% CI, 0.56–1.80), 1.108 (95% CI, 0.63–1.96), and 1.021 (95% CI, 0.57–1.82) for DOC, DC, and OC, respectively. No new safety signals were observed. Conclusions: In patients with PROC with prior bevacizumab, all experimental arms failed to reach the primary objective of improving PFS compared with SOC.

Comprehensive Care of Women With Genetic Predisposition to Breast and Ovarian Cancer

Women at risk for hereditary breast and ovarian cancer syndromes are frequently seen in primary care and gynecology clinics. They present with a distinctive set of clinical and emotional needs that revolve around complex risk management discussions and decision making. The care of these women calls for the creation of individualized care plans that facilitate adjustment to the mental and physical changes associated with their choices. This article provides an update on comprehensive evidence-driven care of women with hereditary breast and ovarian cancer. The aim of this review is to aid clinicians in identifying those at risk for hereditary cancer syndromes and provide practical advice on patient-centered medical and surgical risk management. Topics of discussion include enhanced surveillance, preventive medications, risk-reducing mastectomy and reconstruction, risk-reducing bilateral salpingo-oophorectomy, fertility, sexuality, and menopausal management, with attention to the importance of psychological support. High-risk patients may benefit from a multidisciplinary team that provides realistic expectations with consistent messaging. The primary care provider must be aware of the special needs of these patients and the consequences of their risk management interventions.

Radiofrequency Ablation for the Treatment of Uterine Fibroids: A Systematic Review and Meta-Analysis by the AAGL Practice Committee

To systematically review clinical and patient-reported outcomes after radiofrequency ablation (RFA) for the treatment of uterine fibroids. We searched Medline, EMBASE, Cochrane Registry of Controlled Trials (CENTRAL) on September 8, 2023, and requested additional data from industry sources. We included published, peer-reviewed studies of patient-centered outcomes of RFA when used for symptomatic fibroids. Abstracts and potentially relevant full-text articles were screened and data were extracted regarding study characteristics, arms, outcomes, and results, together with risk of bias assessment. We included 30 studies published in 49 articles (3 randomized controlled trials, 1 nonrandomized comparative study, and 26 single-group studies, as well as 4 publications from the TRUST Study) with variable risks of bias. The study populations were demographically diverse and clinically heterogeneous. Across studies, RFA treatment was associated with fibroid volume reduction of 46.0% (95% confidence interval [CI] 52.1, 40.0; 11 studies) at 3 months and 65.4% (95% CI 74.7, 56.1; 10 studies) at 12 months. All studies reported a decrease in proportion of patients experiencing abnormal, heavy, or prolonged menstrual bleeding, with the most substantial improvement within the first 3 months. Meta-analyses of health-related quality of life scores demonstrated significant improvements in scores from baseline for Uterine Fibroid Symptoms and Quality of Life (53.4, 95% CI 48.2, 58.5; 19 studies), EuroQol-5 dimension (71.6, 95% CI 65.0, 78.1; 4 studies), and Symptom Severity Score (52.2, 95% CI 46.4, 58.1; 17 studies), with a peak at 6 months on the Uterine Fibroid Symptoms and Quality of Life scale (88.0, 95% CI 83.0, 92.9; 11 studies), a peak at 24 months on the EuroQol-5 dimension scale (88.3, 95% CI 86.0, 90.6; 2 studies), and a trough at 12 months for Symptom Severity Score (12.8, 95% CI 7.0, 18.6; 11 studies). Studies mostly demonstrated return to work and normal activities within 2 weeks. Reported unplanned hospitalizations were infrequent, and durations of hospital stay were generally short. Postprocedure complications were inconsistently reported but assessed overall to be infrequent. Long-term need for medical and surgical re-intervention varied. Post-RFA hysterectomy rates ranged from 2/205 (1.0%) to 15/62 (24.1%) with variable follow-up periods ranging from 45 days to 74 months. Most studies did not include patients who desired to maintain fertility; thus, reproductive data are insufficient for interpretation. There is a paucity of comparative studies, and the small number of RCTs are limited by lack of blinding. Few studies had the long-term follow-up time required to draw definitive conclusions regarding the durability of symptom relief. However, despite these limitations, there is overall agreement on several important clinical measures following RFA, such as decreased fibroid volume, improved uterine bleeding, and improved quality of life. Future high-quality randomized controlled trials with standardized outcomes measures are required to better characterize the use of RFA among fibroid patients.