Abstract Salient to the intent of personalized medicine, hereditary cancer syndromes present significant opportunities in the treatment and prevention of some gynecologic cancers. Mutations in BRCA1 ..., BRCA2 , and DNA mismatch repair genes: MLH1 , MSH2 , MSH6 , and PMS2 are important causal agents in hereditary breast and ovarian cancer (HBOC) and Lynch syndromes. Though they only account for an estimated 10-18% of ovarian, tubal, peritoneal, and endometrial cancer cases, inherited cancers are imminently preventable if mutation carriers are identified in a timely manner. Population level screening is currently impractical due to low prevalence of disease, cost of testing, and ethical issues associated with testing, so diagnosis of these mutations is limited. Being affected by one of the heritable gynecologic malignancies is a logical entry point into the genetic counseling and testing pipeline for the patient and her family members. Thus, gynecologic cancer providers are uniquely positioned to diagnose germline mutations that can inform prognosis and treatment for their patients in addition to enabling prevention for patients’ cancer-unaffected blood relatives, or “previvors”. The purpose of this review is to describe our current perspective on testing for and implications of heritable cancer syndromes in the women with ovarian, tubal, peritoneal, and endometrial cancers.
Abstract Objective To characterize the impact of hospital and physician ovarian cancer case volume on survival for advanced-stage disease and investigate socio-demographic variables associated with ...access to high-volume providers. Methods Consecutive patients with stage IIIC/IV epithelial ovarian cancer (1/1/96–12/31/06) were identified from the California Cancer Registry. Disease-specific survival analysis was performed using Cox-proportional hazards model. Multivariate logistic regression analyses were used to evaluate for differences in access to high-volume hospitals (HVH) (≥ 20 cases/year), high-volume physicians (HVP) (≥ 10 cases/year), and cross-tabulations of high- or low-volume hospital (LVH) and physician (LVP) according to socio-demographic variables. Results A total of 11,865 patients were identified. The median ovarian cancer-specific survival for all patients was 28.2 months, and on multivariate analysis the HVH/HVP provider combination (HR = 1.00) was associated with superior ovarian cancer-specific survival compared to LVH/LVP (HR = 1.31, 95%CI = 1.16–1.49). Overall, 2119 patients (17.9%) were cared for at HVHs, and 1791 patients (15.1%) were treated by HVPs. Only 4.3% of patients received care from HVH/HVP, while 53.1% of patients were treated by LVH/LVP. Both race and socio-demographic characteristics were independently associated with an increased likelihood of being cared for by the LVH/LVP combination and included: Hispanic race (OR = 1.72, 95%CI = 1.22–2.42), Asian/Pacific Islander race (OR = 1.57, 95%CI = 1.07–2.32), Medicaid insurance (OR = 2.51, 95%CI = 1.46–4.30), and low socioeconomic status (OR = 2.84, 95%CI = 1.90–4.23). Conclusions Among patients with advanced-stage ovarian cancer, the provider combination of HVH/HVP is an independent predictor of improved disease-specific survival. Access to high-volume ovarian cancer providers is limited, and barriers are more pronounced for patients with low socioeconomic status, Medicaid insurance, and racial minorities.
The year 2023 was an extraordinary year for the further development and expansion of novel treatments for all patients with cervical cancer, ranging from early stage to later stage and metastatic or ...recurrent disease. Individuals with early‐stage disease will benefit from less invasive surgery with subsequent improvement in quality of life. The effectiveness of immunotherapy has been demonstrated in upfront, locally advanced cervical cancer and confirmed in advanced metastatic disease. Induction chemotherapy will play a role in some patients with locally advanced disease, particularly those in low resource areas of the world. Novel therapeutics including antibody–drug conjugates have shown efficacy even in pretreated patients. As we continue to explore innovative therapeutics in this space, however, we must also continue to improve the diversity of clinical trial accrual to allow for generalizable results. At the same time, we must focus on eradicating this disease with appropriate screening and vaccination.
Over the past few years we have seen the remarkable development, refinement, and implementation of innovative therapies for individuals with cervical cancer, ranging from early stage to late stage and recurrent disease. These novel options offer new and more successful therapies for our patients with cervical cancer that will both prolong life and improve quality.
The adjunctive use of intraoperative molecular imaging (IMI) is gaining acceptance as a potential means to improve outcomes for surgical resection of targetable tumors. This confirmatory study ...examined the use of pafolacianine for real-time detection of folate receptor-positive ovarian cancer.
This phase III, open-label, 11-center study included subjects with known or suspected ovarian cancer, scheduled to undergo cytoreductive surgery. The objectives were to confirm safety and efficacy of pafolacianine (0.025 mg/kg IV), given ≥ 1 hour before intraoperative near-infrared imaging to detect macroscopic lesions not detected by palpation and normal white light.
From March 2018 through April 2020, 150 patients received a single infusion of pafolacianine (safety analysis set); 109 patients with folate receptor-positive ovarian cancer comprised the full analysis set for efficacy. In 33.0% of patients (95% CI, 24.3 to 42.7;
< .001), pafolacianine with near-infrared imaging identified additional cancer on tissue not planned for resection and not detected by white light assessment and palpation, exceeding the prespecified threshold of 10%. Among patients who underwent interval debulking surgery, the rate was 39.7% (95% CI, 27.0 to 53.4;
< .001). The sensitivity to detect ovarian cancer was 83%, and the patient false-positive rate was 24.8%. Investigators reported achieving complete R0 resection in 62.4% (68 of 109) of patients. Drug-related adverse events were reported by 30% of patients (45 of 150) and most commonly included nausea, vomiting, and abdominal pain. No drug-related serious adverse events or deaths were reported.
This phase III study of pafolacianine met its primary efficacy end point, identifying additional cancers not otherwise identified or planned for resection. Pafolacianine may offer an important real-time adjunct to current surgical approaches for ovarian cancer.
Cervical cancer is the most commonly diagnosed gynecologic cancer worldwide. Although the incidence has declined with increased screening and higher uptake of human papillomavirus (HPV) vaccination ...in high-income countries, this disease remains the second highest cause of cancer mortality among women in low- and middle-income countries. In this clinical practice statement, we describe therapies for cervical cancer by treatment setting, as well as quality of life, financial toxicity, and disparities associated with this disease. In addition to chemotherapy and radiation, therapeutic strategies for cervical cancer include immune checkpoint blockade, antiangiogenics, and antibody-drug conjugates. Optimal treatment for recurrent cervical cancer remains an area of unmet need, necessitating further exploration of rational and innovative treatment approaches, including cell and immune-based therapies. Importantly, development of effective therapies for cervical cancer must incorporate strategies to ensure universal equitable access to HPV vaccination, screening, and treatment. Important consequences of the disease and treatment that impact quality of life must also be addressed. Patients with cervical cancer are at increased risk for financial toxicity, which can lead to downstream detrimental effects on physical, financial, and career outcomes. Underrepresentation of racial and ethnic minorities in gynecologic oncology clinical trials highlights the urgent need for collaborative and focused initiatives to bridge the significant divide and alleviate inequalities in the prevention and treatment of cervical cancer.
Highlights • The Society of Gynecologic Oncology convened a multidisciplinary Genetics Summit. • The benefits and challenges of genetic risk assessment were discussed. • Minimum standards for genetic ...risk assessment are suggested. • Suggestions for further research and educational efforts are communicated.
Abstract Objectives The purpose of this review is to discuss the side effect profile of bevacizumab, to discuss proposed mechanisms of these toxicities, and to provide suggestions for management of ...adverse events. Methods A search of MEDLINE and ASCO and SGO abstract databases of articles published between January 1970 and August 2009 addressing the toxicity of bevacizumab in solid tumors was conducted. Reporting was limited to best available evidence including any available phase III studies and ovarian cancer phase II studies. Original publications addressing underlying mechanisms of bevacizumab toxicities were included. Results Extensive experience with bevacizumab has proven the agent to be generally well tolerated, with an adverse event profile distinct from traditional cytotoxic chemotherapy and likely peculiar to its novel mechanism of action. The most common bevacizumab-attributable adverse event, hypertension, can be medically-managed, but more serious adverse events such as bowel perforation require drug discontinuation. Conclusions Current best evidence supports the use of bevacizumab in selected patients, and safe administration of bevacizumab requires an understanding of the management of adverse events attributable to its use.
•KN A-18 led to approval of pembrolizumab plus chemotherapy and radiation in treating locally advanced cervical cancer.•Only a subset of those enrolled in the study were included in the indication ...statement.•Regulatory approvals should focus on primary objectives and sound statistical endpoints.
This phase II clinical trial evaluated the safety and antitumor activity of balstilimab, an anti-PD-1 antibody, in patients with previously-treated, recurrent/metastatic cervical cancer.
Eligible ...patients were 18 years or older with recurrent and/or metastatic cervical cancer and who had relapsed after a prior platinum-based treatment regimen for advanced disease. Balstilimab was administered intravenously at 3 mg/kg once every two weeks, for up to 24 months. The primary endpoint was objective response rate (ORR, RECIST v1.1) as assessed by an independent review committee.
At data cutoff, 161 women (median age, 53 years range 25–81) were enrolled and treated with balstilimab. Of these, 140 had measurable disease at baseline and one prior line of platinum-based therapy in the metastatic, persistent, or recurrent setting; these patients were included in the efficacy analyses. The ORR was 15% (95% CI, 10.0%–21.8%) and included 5 patients with a complete response and 16 with a partial response. The median duration of response was 15.4 months. In patients with PD-L1-positive tumors the ORR was 20%, however patients with PD-L1-negative tumors also responded to balstilimab (ORR, 7.9%). Responses were not restricted to tumors of squamous cell histology, and an ORR of 12.5% was seen in the subset of patients with cervical adenocarcinoma. The disease control rate was 49.3% (95% CI, 41.1%–57.5%). Immune-mediated enterocolitis (3.1%) and diarrhea (1.9%) were the most common grade 3 or higher treatment-related adverse events.
Balstilimab demonstrated meaningful and durable clinical activity, with manageable safety, in patients with previously-treated, recurrent/metastatic cervical cancer.
•Balstilimab elicited promising and durable clinical activity in patients with recurrent/metastatic cervical cancer.•Tumor responses occurred irrespective of tumor PD-L1 status or histology.•Balstilimab is well tolerated, with a safety profile consistent with other PD-1 inhibitors.•These findings highlight balstilimab as an attractive candidate for both single-agent and combination-based immunotherapy.
In patients with high-grade ovarian cancer, predictors of bevacizumab efficacy in first-line setting are needed. In the ICON-7 trial, a poor tumor intrinsic chemosensitivity (defined by unfavorable ...modeled cancer antigen-125 CA-125 ELIMination rate constant K KELIM score) was a predictive biomarker. Only the patients with high-risk disease (suboptimally resected stage III, or stage IV) exhibiting unfavorable KELIM score < 1.0 had overall survival (OS) benefit from bevacizumab (median: 29.7
20.6 months; hazard ratio HR, 0.78). An external validation study in the GOG-0218 trial was performed.
In GOG-0218, 1,873 patients were treated with carboplatin-paclitaxel ± concurrent-maintenance bevacizumab/placebo. Patient KELIM values were calculated with CA-125 kinetics during the first 100 chemotherapy days by the Lyon University team. The association between KELIM score (favorable ≥ 1.0, or unfavorable < 1.0) and bevacizumab benefit for progression-free survival (PFS)/OS was independently assessed by NGR-GOG using univariate/multivariate analyses.
KELIM was assessable in 1,662 patients with ≥ 3 CA-125 available values. An unfavorable KELIM score was associated with bevacizumab benefit compared with placebo (PFS: HR, 0.70; 95% CI, 0.59 to 0.82; OS: HR, 0.87; 95% CI, 0.73 to 1.03), whereas a favorable KELIM was not (PFS: HR, 0.96; 95% CI, 0.79 to 1.17; OS: HR, 1.11; 95% CI, 0.89 to 1.39). The highest benefit was observed in patients with a high-risk disease exhibiting unfavorable KELIM, for PFS (median: 9.1
5.6 months; HR, 0.64; 95% CI, 0.53 to 0.78), and for OS (median: 35.1
29.1 months; HR, 0.79; 95% CI, 0.65 to 0.97).
This GOG-0218 trial investigation validates ICON-7 findings about the association between poor tumor chemosensitivity and benefit from concurrent-maintenance bevacizumab, suggesting that bevacizumab may mainly be effective in patients with poorly chemosensitive disease. Bevacizumab may be prioritized in patients with a high-risk and poorly chemosensitive disease to improve their PFS/OS (patient KELIM score calculator available on the Biomarker Kinetics website).
PDF
