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Global Trends In Ovarian Cancer Incidence Highlight Regional, Histological Variations
Between 1988 and 2017, there were significant global variations and trends in ovarian cancer incidence and its subtypes, influenced by genetic, reproductive, and socioeconomic factors.
Variations in global patterns and trends of ovarian cancer (OC) incidence and its subtypes were observed between 1988 and 2017, with potential influence from genetic and reproductive factors, according to a study published in eClinicalMedicine.1
Despite declining OC incidence rates over the past few decades, particularly in high-income countries, OC prognosis remains dismal, with age-standardized 5-year net survival rates varying between 30% and 50% in most countries.2 However, only 3 studies have investigated the global patterns or trends of OC incidence, both overall and by histological subtype.1
Due to the limited scope of these studies and the changes in OC diagnostic techniques and risk factors, the researchers of the present analysis stressed the need for up-to-date comprehensive epidemiological data on global patterns and trends of OC incidence and its histological subtypes. They aimed to provide this update by computing annual percent changes (APCs) to describe global trends in age-standardized rates (ASRs) of OC and its subtypes. They also calculated the proportions of ASR for each subtype relative to the ASR of OC for individual countries.
Between 1988 and 2017, there were significant global variations and trends in ovarian cancer incidence and its subtypes.Image Credit: flashmovie - stock.Adobe.Com
To do so, the researchers extracted all data from the most recent entry into the Cancer Incidence in 5 Continents database (C15 Volume XII) and the C15plus database. Published every 5 years since the 1960s by regional and national cancer registries worldwide, the C15 series contains high-quality information on new cancer cases by site, registry, sex, 5-year age group, and histology (if available), together with age-specific populations.
They obtained historical data (1988-2012) from the C15plus database and the most recent data (2013-2017) from the C15 database. Based on available registries in the C15 Volume XII database, international patterns for OC incidence and its histological subtypes were described by country, world region, and human development index (HDI) from 2013 through 2017.
The HDI is based on 3 fundamental characteristics of human development: being knowledgeable, having a long and healthy life, and having a decent standard of living. Based on their HDI values between 2013 and 2017, countries were divided into 4 groups (very high, high, medium, and low) to examine the patterns of OC incidence vs human development.
International trends of OC incidence and its histological subtypes also were calculated every 5 years between 1988 and 2017. Eligible countries were included in C15 Volume XII and had at least 15 consecutive years of data. Therefore, 65 and 40 countries from 5 continents were eligible for pattern description and trend analysis, respectively.
The researchers categorized the world regions as Africa, Asia, North America, South America, Eastern Europe, Western Europe, Southern Europe, Northern Europe, Central Europe, and Oceania. Also, they categorized the OC histology subtypes as serous carcinoma, endometrioid carcinoma, mucinous carcinoma, clear cell carcinoma, adenocarcinoma not otherwise specified (NOS), other epithelial OC (EOC), germ cell tumor (GCT), sex cord-stromal tumor (SCST), and other tumors.
In the most recent period (2013-2017), the researchers detected the highest ASRs of OC in Eastern Europe, followed by Central and Southern Europe. More specifically, the highest ASRs occurred in Latvia (15.53 per 100,000 person-years) and Lithuania (13.28 per 100,000 person-years). Conversely, they detected the lowest ASRs in Africa and Asia, with the lowest recorded in Benin (3.26 per 100,000 person-years).
Also, the highest ASR occurred in very high HDI regions (8.22 per 100,000 person-years), while the lowest ASR was seen in areas with medium HDI values (5.52 per 100,000 person-years).
As for OC incidence trends, significant decreases in ASRs were found in 19 of 40 countries between 1988 and 2017, with the APC ranging from −0.46 to −2.87. Within all countries examined in Northern Europe, Western Europe, and Oceania, ASRs decreased from high to intermediate rates. The largest declines occurred in Iceland (APC, −2.87; 95% CI, −4.80 to −0.90), the Netherlands (APC, −1.75; 95% CI, −2.86 to −0.63), and New Zealand (APC, −1.66; 95% CI, −2.35 to −0.96).
Similarly, the ASRs in Eastern Europe, North America, and South America steadily decreased, with substantial reductions in Estonia (APC, −0.56; 95% CI, −1.04 to −0.09), Canada (APC, −0.80; 95% CI, −1.03 to −0.56), the US (APC, −1.47; 95% CI, −1.71 to −1.23), and Colombia (APC, −1.00; 95% CI, −1.91 to −0.08).
As for Southern and Central Europe, some countries maintained a steady trend while others experienced significant declines. The researchers observed noteworthy decreases in Austria (APC, −2.40; 95% CI, −3.22 to −1.57), Germany (APC, −1.15; 95% CI, −1.93 to −0.37), and Switzerland (APC, −1.22; 95% CI, −1.58 to −0.86). Although most Asian regions exhibited stable temporal trends, several countries, like Japan (APC, 1.90; 95% CI, 1.32-2.50) and South Korea (APC, 1.18; 95% CI, 0.82-1.53), showed significant upward trends.
In terms of OC histological subtypes, serous carcinomas consistently exhibited the highest ASRs among most countries assessed, especially in Europe; Lithuania recorded the highest ASR at 6.59 per 100,000 person-years. However, the ASRs of mucinous carcinomas were particularly high the Asian countries of Brunei (2.59 per 100,000 person-years), the Philippines (1.12 per 100,000 person-years), and Singapore (1.12 per 100,000 person-years); Asian regions also had higher ASRs of endometrioid and clear cell carcinomas.
Globally, serous carcinomas constituted 37.66% of the total OC ASR, followed by other tumors (13.17%), adenocarcinoma NOS (12.77%), other EOC (8.64%), endometrioid carcinomas (7.76%), mucinous carcinomas (7.00%), clear cell carcinomas (5.94%), GCT (4.78%, and SCST (2.25%).
The researchers acknowledged their study's limitations, including the absence of national cancer registries in several countries. Consequently, they combined regional cancer registries to approximate the national profiles of these countries; this may have resulted in relative underrepresentation. Despite their limitations, the researchers suggested areas for further research based on their findings.
"Further research is necessary to definitively identify the specific factors driving these variations in OC incidence across different countries, ultimately enabling the development of region-specific prevention and control strategies to effectively mitigate the global burden of this disease," the authors concluded.
References
1. Wei YF, Ning L, Xu YL, et al. Worldwide patterns and trends in ovarian cancer incidence by histological subtype: a population-based analysis from 1988 to 2017. EClinicalMedicine. 2024;79:102983. Doi:10.1016/j.Eclinm.2024.102983
2. Allemani C, Matsuda T, Di Carlo V, et al. Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37,513,025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet. 2018;391(10125):1023-1075. Doi:10.1016/S0140-6736(17)33326-3
NXP-800 By Nuvectis Pharma For Ovarian Cancer: Likelihood Of Approval
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Novel CAR T-Cell Therapy Trial Advances To Third Cohort In Ovarian Cancer
A phase 1 trial evaluating FSHR-targeting CAR T cells for patients with ovarian cancer has dosed the first patient in its third cohort.
Illustration of ovarian cancer: © blueringmedia - stock.Adobe.Com
The first patient has been dosed with a novel chimeric antigen receptor (CAR) T-cell therapy in the third cohort of an ongoing phase 1 trial for patients with ovarian cancer.1
The first-in-human study, which is being conducted through a research partnership with Moffitt Cancer Center, is evaluating the safety of treatment with autologous T cells genetically modified to express a chimeric endocrine receptor (CER) targeting the follicle-stimulating hormone receptor (FSHR), with or without conditioning chemotherapy, in patients with ovarian cancer.1,2
In the initial cohort which included 3 patients, there were no dose-limiting toxicities (DLT) reported.The same was true for the second 3-patient cohort, where patients were given a CAR T-cell dose triple that of the first cohort.1
Following the required 1-month observation period to evaluate DLT and review all safety data, the trial has progressed to dosing its first patient in the third cohort. Here, investigators are administering a tenfold increase over the initial dose.
"With no dose-limiting safety issues observed in the first and second patient cohorts, we have advanced to the next cohort to evaluate a 10x higher dose compared with the starting dose. As the trial continues, our aim is to demonstrate the tolerability of our CAR T but we are optimistic and hopeful about seeing efficacy in this solid tumor—a challenging area for traditional CAR T therapies, which have shown efficacy mainly in hematologic tumors and lymphomas. We are very encouraged how the trial has progressed and our observation in one patient from the first cohort who had relative stability and even some mild improvement for well over a year after her infusion," said Robert Wenham, MD, principal investigator of the study and chair of the Department of Gynecologic Oncology at Moffitt, in a press release.
Patients will receive 1 infusion of FSHR T cells at varying dose levels and through different administration methods. For the intraperitoneal treatment arms, patients are being given these T cells at 5 dose levels, with the first group receiving a dose of 1 x 105. The infusion will be delivered through a thin membrane of the abdominal cavity. The second dose level will involve 3 x 105 FSHR T cells, again administered intraperitoneally. The third dose level will increase to 1 x 106 FSHR T cells, followed by a fourth dose level of 3 x 106 FSHR T cells. The fifth dose level will involve the highest dose of 1 x 107 FSHR T cells, all via intraperitoneal infusion.2
In the intravenous (IV) treatment arms, patients will receive the FSHR T cells in a similar fashion, given at the same dose levels but administered via IV infusion. Dose Level 1 will involve 1 x 105 FSHR T cells, followed by 3 x 105 at dose level 2. The third dose level will be 1 x 106 FSHR T cells, with the fourth dose level at 3 x 106 cells. The final dose level will consist of 1 x 107 FSHR T cells administered IV.2
Enrollment in the study is open to patients 18 years of age and older with a pathologically confirmed diagnosis of high-grade epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube carcinoma. Patient's disease must be serous, endometrioid, clear cell, mucinous, mixed epithelial, or undifferentiated and those with tumors that are substantially high-grade carcinoma and have focal elements of lower grade tumors or sarcomatous elements are eligible for enrollment. Further, patients are required to have measurable or detectable disease, carcinoma that expresses the FSHR antigen, an ECOG performance status of 2 or better, a life expectancy of at least 3 months, and adequate bone marrow, renal, and hepatic function.
Additional inclusion criteria requires patients to have had 1 previous platinum-based chemotherapeutic regimen for the management of ovarian, primary peritoneal, or fallopian tube carcinoma and at least 2 prior chemotherapy regimens, be considered platinum- refractory or resistant, deemed unlikely to have significant benefit from any standard therapies by the treating investigator, and have received no anticancer therapy in the 3 weeks prior to infusion with the T-cell. Patients must not have received prior immunotherapy with checkpoint blockade in the 6 months before the T-cell infusion, and those with a known germline or somatic BRCA pathogenic mutation should have received a prior PARP inhibitor and subsequent progression, unless they have a documented history of intolerance or inability to swallow oral medications.
While not required, patients are allowed to receive up to 6 additional prior chemotherapy treatment regimens or biologic/targeted therapy alone or as part of their treatment regimens. Further, patients must agree to undergo the placement of an interventional radiologically placed or surgically placed peritoneal port.
The primary end point is to determine the maximum tolerated dose of FSHR T cells and secondary end points include duration of response, duration of stable disease, and overall survival.
"This is highly unusual for a platinum resistant multiply treated ovarian cancer. A tumor biopsy showed necrosis and T-cell infiltration. Based on these findings, we recently submitted an amendment to the trial protocol to allow patients who may benefit from an additional dose. Generally, we expect higher cell doses to increase efficacy, although we also anticipate a second dose may further improve response rates and durability. We are proud of the progress to date and look forward to treating additional patients in the third cohort," added Wenham in the press release.1
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