Fallopian Tube Cancers, Fallopian Tube Cancer Stage III, Fallopian Tube Cancer Stage IV, Ovarian Cancer by FIGO Stage, Ovarian Cancer Stage III, Ovarian Cancer Stage IV
Conditions
Keywords
Peritonial Cancer
Brief summary
This is a multicentric observational study conducted at selected sites across Latin America. Eligible participants will be identified through the medical records of participating institutions. The study aims to describe overlap of expression of folate receptor alpha (FRα), HER2 and PD-L1 using immunohistochemistry (IHC) and HRD and BRCA (somatic and germline) by NGS. Additionally, to describe clinical demographic and socioeconomic variables, as well as treatment patterns, pathological characteristics, outcomes, and genetic and molecular testing part of clinical practice. All data (including patient characteristics, treatment patterns, outcomes and available tests) will be collected once, retrospectively from medical records, ensuring adherence to ethical standards and participant confidentiality. Biomarkers analysis (including FRα, HER2 and PD-L1) will be performed prospectively, a Formalin-Fixed Paraffin-Embedded (FFPE) tumor block will be collected to evaluate and describe the expression of folate receptor alpha (FRα) and HER2, using immunohistochemistry (IHC) with the Roche Ventana kit (FOLR1 and HER2 4B5) and Dako's 22C3 for PD-L1. The study will analyze samples collected between 1st January 2018 to 31 December 2024 (analysis of historically collected samples). The study comprises a retrospective data collection from medical charts. Participants will continue to receive treatment and clinical evaluations according to what is determined by their medical team, according to the usual standards of treatment and clinical practice of each center. No intervention or prospective follow-up is proposed in this study.
Detailed description
The study combines a retrospective collection of clinical, sociodemographic, pathological, and treatment history data from medical records with a prospective laboratory analysis of archived tumor tissue samples collected between 2018 and 2024. Biomarker Evaluation & Central Pathology: Archival formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks or unstained slides will undergo centralized digital pathology review and immunohistochemical (IHC) evaluation to assess expression levels: * Folate Receptor Alpha (FRa): Assessed using the Roche Ventana FOLR1 assay. * HER2: Evaluated using the Roche Ventana HER2 (4B5) assay. * PD-L1: Evaluated using Dako 22C3. * Additional exploratory IHC markers (ER, PR, MLH1, MSH2, MSH6, PMS2) will also be evaluated. Genetic and molecular status for BRCA1/2 mutations and Homologous Recombination Deficiency (HRD) obtained via Next-Generation Sequencing (NGS) will be extracted retrospectively from medical records as available in routine clinical practice. All clinical and historical data will be abstracted once retrospectively from participant charts and recorded electronically using a validated REDCap Electronic Data Capture (EDC) system. The study design involves no prospective clinical follow-up or therapeutic interventions; all participants continue standard-of-care treatment as dictated by their treating physicians. An interim statistical analysis is planned after 50% of the target sample in Brazil has completed baseline assessments, followed by a final analysis upon full study completion.
Interventions
None listed
Sponsors
Latin American Cooperative Oncology Group
AbbVie
EVA - Grupo Brasileiro de Tumores Ginecológicos
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participants ≥18 years-old. 2. Patients diagnosed with ovarian, fallopian tube or peritoneal cancer: 1. advanced stages stage III or IV by FIGO disease stage 2. new diagnosis and persistent or recurrent disease 3. Diagnosed from 2018 to 2024. 4. Histologically confirmed diagnosis of serous (low or high grade), endometrioid, mucinous or clear cell ovarian carcinoma. 5. Accept to participate in the project and sign the informed consent (if applicable). 6. An archived representative formalin-fixed paraffin-embedded (FFPE) tumor specimen in tumor tissue blocks (preferred) or freshly sectioned unstained slides (at least 20) from biopsy/surgery is mandatory.
Exclusion criteria
1. Histological ambiguous diagnosis upon review. 2. Diagnosis based on cytology and without any biopsy or surgical specimen. 3. Patients diagnosed and staged but not receiving any treatment. 4. Patients without medical records available (lost, empty or irretrievable clinical information).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of high-grade serous advanced ovarian cancer (AOC) cases overlapping FRα, HER2, PD-L1 positive expression and aberration positives for HRD and BRCA. | Data is extracted from retrospective medical records covering cases diagnosed from 2018 to 2024, with no prospective clinical follow-up or therapeutic interventions proposed. | The percentage of high- grade serous AOC cases which are overlapping FRα, HER2, PD-L1 positive expression by IHC according to established clinical cut-offs and aberration positives for HRD and BRCA: FRα: ≥75% of viable tumour cells with 2+ and 3+ scoring intensity. HER2: ≥10% of viable tumour cells with 3+ staining intensity by IHC using current CAP guidelines for scoring HER2 in gastric cancer. PD-L1: positive expression is combined positive score (CPS) ≥1 and ≥10. BRCA mutational status: mutated. HRD: positive. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Socio-demographic and clinicopathologic characteristics of Latin American advanced ovarian cancer (AOC) patients. | Baseline | Description and summarization of socio-demographic and clinicopathologic characteristics (including histological subtypes) of the study population, presented as frequencies and percentages. |
| Treatment patterns of high-grade serous advanced ovarian cancer (AOC). | Baseline | Description of treatment patterns by absolute numbers and percentages of patients, including type of treatment (surgery procedures, chemotherapy regimens, target therapies such as bevacizumab-based or PARP inhibitor-based, and best supportive care \[BSC\]) stratified by line of treatment (first line \[1L\] and second line \[2L\] or more) to define the median number of therapies. It also evaluates the time to first treatment, defined as the duration from the high-grade serous AOC diagnosis until the administration of the first treatment. |
| Folate receptor alpha (FRα), HER2, and PD-L1 expression by histologic advanced ovarian cancer (AOC) subtype. | Baseline | Evaluation of the percentage (absolute numbers) of ovarian cancer cases expressing FRα, HER2, and PD-L1 by immunohistochemistry (IHC) across different histological groups (Serous \[low and high grade\], endometrioid, clear cell, and mucinous). FRα expression will be evaluated using the VENTANA FOLR1 kit at two thresholds of viable tumor cells (TC) with membrane staining at moderate (2+) and/or strong (3+) intensity levels: ≥50% and ≥75%. |
| Mutational status of HRD and BRCA in high-grade serous advanced ovarian cancer (AOC). | Baseline | Evaluation of the percentage (absolute number) of Latin American patients with high-grade serous AOC exhibiting alterations in homologous recombination deficiency (HRD) status (positive/deficiency vs. negative/proficiency) and BRCA mutational status (mutated vs. wild-type) collected from Next-Generation Sequencing (NGS) data available in medical records. |
Countries
Argentina, Brazil, Colombia, Mexico
Contacts
CONTACTProject Manager
CONTACTLaura Voelcker
PRINCIPAL_INVESTIGATORAngélica Rodrigues
Oncocentro de Minas Gerais
Outcome results
None listed