Search

Lack of patient diversity in clinical trial enrollment remains an obstacle to achieving equitable healthcare outcomes. Under-representation has resulted in non-generalizable clinical knowledge, inequitable access to treatment, and health disparities among minority and disadvantaged groups. A multidisciplinary panel was convened to consider the challenges of diverse patient accrual and provide actionable solutions to improve representation in clinical trials. The panel was comprised of participants with knowledge in gynecologic oncology and included physician, advanced practice nurse, patient navigator, patient advocate, and pharmaceutical industry representation. Focus was given to recruitment barriers for Asian and Hispanic patients. The panel identified several areas of concern, including explicit and implicit biases for the physician and care teams, language and cultural nuances, inadequate inclusion of family in the decision-making process, and under-representation of women in clinical trials. The panel also identified the important role patient navigators, nurses, and advanced practice providers have in patient recruitment from under-represented populations. The role of study sponsors, and global and regional initiatives, to address historic disparities in clinical trial recruitment were also considered critical. The actionable solutions proposed should enable study sponsors and clinical trial sites to achieve greater diversity in enrollment globally., Competing Interests: Competing interests: BP has received grants from Tesaro/GSK, Merck, Astra Zeneca, Karyopharm Therapeutics, Incyte, Toray, VBL Therapeutics, InxMed, Agenus, Clovis Oncology, Roche/Genentech, Mersana, Celsion/Immunon, I-Mab, Takeda, Onconova, Celgene, Sutro Biopharma, Novocure, Seagen, NRG Oncology, Duality Bio, Xencor, Immunogen, Eisai, Acrivon, and Alkermes; consulting fees from Tesaro/GSK, Astra Zeneca, Merck, Immunogen, GOG Foundation, Seagen, Lilly, Eisai, Signatera, Celsion, Sutro Biopharma, Imvax, Incyte, InxMed, Onconova Therapeutics, R-Pharm, Regeneron, and Duality Bio; honoraria from Bioascend, PERS, Vanium, Curio, OncLive, Yale University, and PeerView; support for attending meetings and/or travel from GOG Partners; participated on data safety monitoring boards (DSMBs) or advisory boards for Sutro Biopharma, Astra Zeneca, GOG Foundation, Celsion/Immunon, Toray, InxMed, Onconova, Imvaz, I-Mab, Tesaro/GSK, Merck, Mersana, Nuvation, and BioNTech; and served as SGO Clinical Practice Committee Chair, SGO Board of Directors, SGO COVID-19 Taskforce Co-chair, GOG Partners, and NYOB Society Second Vice President. PT has received grants (paid to the institution) from Merck and GSK; participated on DSMBs or advisory boards for Iovance, Astra Zeneca, Verastem, GSK, Seagen, Immunon, Immunogen, Mersana, Novocure, Zentalis, Caris, and Merck; and holds stock or stock options in Immunon. AM has received honoraria and travel fees from Foundation for Women’s Cancer and served as President of Endometrial Cancer Action Network for African Americans. KM has received consulting fees from Eisai. DC has received honoraria from Antibacterial Resistance Leadership Group (ARLG); grants from Duke University for COMET study (cancer) Patient Leadership Group, UCSF for STORMing Cancer Patient Advocate Team, and MD Anderson for PRECISION Patient Advisory Involvement Panel; consulting fees from SimBioSys, MaxisHealth, Health Literacy Media (HLM; as Patient Advisor), Apellis Pharmaceuticals, and Kinnate Biopharma; honoraria and travel support from HMP Education; support for travel from Agile Falcon Strategic Group, DGE Events, and Informa; participated on DSMBs for American Society for Clinical Oncology and on Patient Partner Council for Evidera; has a role on Executive Group for Metastatic Breast Cancer Alliance and a role as committee member for Alliance for Clinical Trials in Oncology; and received manuscript writing support from IQVIA through Regeneron. KL has received fees for participation on advisory boards for Astra Zeneca, Merck, and Eisai. MCM is an employee and stockholder of Incyte. BS has received consulting fees from Astra Zeneca, Clovis, GSK, Genentech, Lilly, Novartis, Gilead, Seagen, Karyopharm, Addy, Circulogene, GOG Foundation, Merck, Imvax, EQRx, and Nuvation; and honoraria from Seagen., (© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Background: Patients with advanced/recurrent endometrial cancer have a poor prognosis and limited treatment options. Biomarkers such as tumor protein 53 ( TP53 ) in endometrial cancer can integrate novel strategies for improved and individualized treatment that could impact patient outcomes. In an exploratory analysis of the phase III ENGOT-EN5/GOG-3055/SIENDO study of selinexor maintenance monotherapy 80 mg in advanced/recurrent endometrial cancer, a pre-specified subgroup of patients with TP53 wild type (wt) endometrial cancer showed preliminary activity at long-term follow-up with a generally manageable safety profile (median progression-free survival 27.4 months vs 5.2 months placebo, HR=0.41)., Primary Objective: To evaluate the efficacy of selinexor compared with placebo as maintenance therapy in patients with advanced or recurrent TP53 wt endometrial cancer., Study Hypothesis: Selinexor administered at 60 mg weekly as maintenance therapy will show manageable safety and maintain efficacy in patients with TP53 wt advanced/recurrent endometrial cancer after systemic therapy versus placebo., Trial Design: This is a prospective, multicenter, double-blind, placebo-controlled, randomized phase III study designed to evaluate the efficacy and safety of selinexor as a maintenance therapy in patients with advanced or recurrent TP53 wt endometrial cancer., Major Inclusion/exclusion Criteria: Eligible patients must have histologically confirmed endometrial cancer, TP53 wt confirmed by next-generation sequencing, completed at least 12 weeks of platinum-based therapy with or without immunotherapy, with confirmed partial response or complete response, and primary Stage IV disease or at first relapse., Primary Endpoint: The primary endpoint is investigator-assessed progression-free survival per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in the intent-to-treat population., Sample Size: A total of 220 patients will be enrolled., Estimated Dates for Completing Accrual and Presenting Results: Accrual is expected to be completed in 2024 with presentation of results in 2025., Trial Registration: NCT05611931., Competing Interests: Competing interests: IV reports consulting for Agenus, Akesobio, AstraZeneca, Bristol Myers Squibb, Deciphera Pharmaceuticals, Eisai, Elevar Therapeutics, F. Hoffmann-La Roche, Genmab, GSK, Immunogen, Jazzpharma, Karyopharm, Mersana, MSD, Novocure, Novartis, Oncoinvent, OncXerna, Sanofi, Regeneron, Seagen, Sotio, Verastem Oncology, Zentalis. APF has received grants/research support from AstraZeneca, Pharmamar, GSK (paid to the institution); participation in a company-sponsored speaker’s bureau for AstraZeneca, MSD, Eisai, GSK, Clovis, Pharmamar, Pharma&; and honoraria or consultation fees from GSK, Clovis, AstraZeneca, Pharmamar, Roche, MSD, Ability Pharma. BJM has received honorarium and consulting fees from Acrivon, Adaptimmune, Agenus, Akeso Bio, Amgen, Bayer, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, Heng Rui, ImmunoGen, Karyopharm, Iovance, Laekna Health Care, Mersana, Myriad, Novartis, Novocure, OncoC4, Panavance, Pieris, Pfizer, Puma, Regeneron, Sorrento, US Oncology Research, VBL, Verastem, Zentalis; and speaker/consultant fees from AstraZeneca, Clovis, Easai, Merck, Roche/Genentech, TESARO/GSK. TH reports scientific advisory board participation: Aadi, AZ, Caris, Clovis, Corcept, Epsilogen, Eisai, Genentech, GSK, J&J, Merck, Seagen. GV reports grants or contracts from advisory boards of AZ, MSD, Clovis, GSK Pharmamar, Eisai. Consulting fees, honoraria, and support for attending meetings from advisory boards of AZ, MSD, Clovis, GSK, Pharmamar, Eisai. DC has nothing to disclose. NC reports fees for advisory board membership for AstraZeneca, Clovis Oncology, Eisai, GSK, Immunogen, Mersana, MSD/Merck, Nuvation Bio, Oncxerna, Pieris, Roche, Novocure; fees as an invited speaker for AstraZeneca, Clovis Oncology, GSK, MSD/Merck, Eisai; institutional research grants from AstraZeneca, Roche, GSK; non-remunerated activities as member of the ESMO Guidelines Steering Committee and chair of the Scientific Committee of ACTO (Alleanza contro il tumore Ovarico). BP reports grants, advisory board, and consultant fees; institutional PI for industry sponsored trials from Tesaro/GSK, AstraZeneca, Merck, Genetech/Roche, Celsion, Karyopharm, Mersana, Takeda Pharmaceuticals, Toray, Imab, Sutro, SeaGen, Clovis Oncology. Compensated advisory boards include Tesaro/GSK, AstraZeneca, Lily, Mersana, Onconova, Merck, Clovis Oncology, Eisai, Toray, Sutro, Deciphera, Imab, SeaGen, GOG Foundation. JS reports research funding: Institution: AZ, Clovis Oncology, Merck, Bayer, PharmaMar, Pfizer, Tesaro, MSD Oncology, Roche. Consulting/advisory boards: AZ, Clovis Oncology, PharmaMar, Merck, Pfizer, Tesaro, MSD Oncology, Lilly, Novocure, J&J, Roche, Ingress Health, Riemser, Sobi, GSK, Novartis; honoraria: AZ, Eisai, Clovis Oncology, Olympus Medical Systems, J&J, PharmaMar, Pfizer, Teva, Tesaro, MSD Oncology, GSK, Bayer. Travel, accommodation, expenses: AZ, Clovis Oncology, PharmaMar, Roche Pharma AG, Tesaro, MSD Oncology, Olympus. JK has nothing to disclose. JB reports participation on advisory boards for AstraZeneca, Clovis, Mersana, OncoC4, Immingen. Speaker's bureau for AstraZeneca, Merck. CP reports honoraria from Novartis, Astra Zeneca, Genesis, MSD Oncology, Servier, WinMedica; has received fees for consulting or advisory role from Amgen, Astellas, BioPharma, Roche Hellas, Astra Zeneca; and research funding from Roche Hellas, WinMedica, Servier. TvG has received grants/research supports (all paid to institution) from Amgen, AstraZeneca, Roche; advisory board (all paid to institution): AstraZeneca, BioNTech, Eisai, GSK, ImmunoGen, Incyte, Karyopharm, MSD, OncXerna, Seagen, Tubulis, Zentalis; participation in a company sponsored speaker’s bureau (all paid to institution): GSK, ImmunoGen, MSD. DR has received fees for advisory boards from Mersana, GlaxoSmithKline, AstraZeneca, ProfoundBio, Eisai, Immunogen. Grants/research supports paid to institution from GlaxoSmithKline, Lilly, Celsion, Mersana, Hookipa, Syros, AstraZeneca, Shattuck Labs, ProfoundBio, CanariaBio, Immunogen, Karyopharm. MMC has nothing to disclose. YA has received grants/research supports from AstraZeneca; honoraria or consultation fees from AstraZeneca; MSD, Eisai, GSK. Consulting or advisory role with AstraZeneca, Eisai, MSD, GSK, Pfizer. MRM has received grants/research supports from AstraZeneca (institution); Boehringer Ingelheim (institution); Pfizer (institution); Tesaro (institution); honoraria or consultation fees from honoraria: Advaxis, AstraZeneca, Cerulean Pharma, Clovis Oncology, Novocure, Pfizer, Roche, Tesaro; consulting or advisory role: AstraZeneca, BioCad, Cerulean Pharma, Clovis Oncology, Genmab, Karyopharm Therapeutics, Novocure, Pfizer, Tesaro; stock shareholder: Karyopharm Therapeutics, SeraCare; and leadership: Karyopharm Therapeutics. KL is an employee of Karyopharm Therapeutics. PK is an employee of Karyopharm Therapeutics. BS reports consulting or advisory roles for Genentech, Eisai, AstraZeneca, Karyopharm Therapeutics, Incyte, Clovis Oncology, Myriad Genetic Laboratories Inc., GlaxoSmithKline LLC, AbbVie Inc., Seagen Inc., Novocure Inc., Novartis, Immunogen, Agenus, Merck Sharp & Dohme, GOG Foundation. RLC has received grant/research support from AstraZeneca/MedImmune (institution), Clovis Oncology (institution), Merck (institution), Roche/Genentech (an immediate family member), Immunogen (institution), Mirati Therapeutics (institution), Amgen (institution), Pfizer (institution), Lilly (institution), Regeneron (institution); honoraria or consulting fees from Clovis Oncology, Genentech/Roche, AstraZeneca/MedImmune, Genmab, OncoMed, Immunogen, AbbVie, Agenus, Novocure, Merck, OncXerna Therapeutics, Alkermes, Gradalis, GlaxoSmithKline, Eisai, GOG Foundation, Karyopharm Therapeutics; stock shareholder from McKesson; and is employed by US Oncology. Leadership: Onxeo. Travel, accommodation, expenses: Merck, AstraZeneca/MedImmune, Array BioPharma, Clovis Oncology, Roche/Genentech, Research to Practice, GOG Foundation, Clovis Oncology, Sotio, Vaniam Group., (© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Metastatic or recurrent endometrioid adenocarcinoma of the uterine corpus is often incurable with limited treatment options. First-line treatment often includes cytotoxic chemotherapy, which incurs significant toxicities for many patients. Endometrial cancer, specifically endometrioid cancer, is a hormone-sensitive disease and, while single-agent hormonal therapies have demonstrated clinical benefit, resistance to these agents often leads to the use of chemotherapy. There is a lack of approved endocrine treatment options in the metastatic setting for most recurrent endometrial cancers, representing an unmet clinical need. Emerging evidence suggests that hormonal therapy in combination with other targeted treatments, such as cyclin dependent kinase (CDK)4/6 inhibitors, is well tolerated and effective in select patient populations. We discuss the clinical evidence suggesting that the combination of CDK4/6 inhibitors and hormonal therapy has the potential to represent an important addition to the first-line treatment options for patients with low-grade advanced or recurrent endometrial cancer., Competing Interests: Competing interests: The authors disclose the following potential conflicts of interest: IR-C: Grants or contracts from any entity: MSD, Roche, BMS, Novartis, AstraZeneca, Merck Sereno; Consulting fees: Abbvie, Agenus, Advaxis, BMS, PharmaMar, Genmab, Pfizer, AstraZeneca, Roche, GSK, MSD, Deciphera, Mersena, Merck Sereno, Novartis, Amgen, Tesaro and Clovis, Adaptimmun, DAICHI Sankyo, ESAI, Immunogen, Seagen, Blueprint, Takeda, Chugai; Travel support: Roche, AstraZeneca, MSD, ESAI, GSK; Participation on a Data Safety Monitoring Board or Advisory Board: Athena, ATTEND, AGOOVAR57; MITO25; Leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid: Chair GINECO. DL: Consulting fees: AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Seagen, Novartis, PharmaMar; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events: AstraZeneca, Clovis Oncology, GSK, MSD, PharmaMar; Payment for expert testimony: Clovis Oncology; Support for attending meetings and/or travel: AstraZeneca, Clovis Oncology, GSK; Participation on a Data Safety Monitoring Board or Advisory Board: Seagen, Immunogen, Genmab, Oncoinvest, Corcept, Sutro, AstraZeneca, GSK; Leadership or fiduciary role in other board, society, committee, or advocacy group, unpaid: GCIG, Member, Board of Directors; Receipt of equipment, materials, drugs, medical writing, gifts, or other services (payments made to institution): Clovis Oncology, GSK, MSD, PharmaMar; Institutional funding for work in clinical trials: AstraZeneca, Clovis Oncology, GSK, MSD, Genmab, PharmaMar, Seagen, Immunogen, Novartis, Roche, Incyte. VU: Stock or stock options: EQRx. RG: Stock or stock options: EQRx, Ironwood Pharmaceuticals, Cyclerion. AH: Stock or stock options: EQRx, Bolt Biotherapeutics, Roche. BJM: Consulting fees: Acrivon, Adaptimune, Agenus, Akeso Bio, Amgen, Aravive, AstraZeneca, Bayer, Clovis, Easai, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, Heng Rui, ImmunoGen, Karyopharm, Iovance, Laekna, Macrogenics, Merck, Mersana, Myriad, Novartis, Novocure, OncoC4, Panavance, Pieris, Pfizer, Puma, Regeneron, Roche/Genentech, Sorrento, TESARO/GSK, US Oncology Research, VBL, Verastem, Zentalis; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events: AstraZeneca, Easai, Myriad, Roche/Genentech, TESARO/GSK. BS: Consulting fees: AstraZeneca, Clovis, GSK, Genentech, Lilly, Novartis, Gilead, Seagen, Karyopharm, Addy, Circulogene, GOG Foundation, Merck, Imvax, EQRx, Nuvation; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events: Seagen. The remaining authors declare no conflicts of interest., (© IGCS and ESGO 2023. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Endometrial cancer is the most common gynecologic malignancy in developed countries, with increasing incidence and mortality rates worldwide. While most cases are successfully treated with surgery, first-line treatment options for metastatic or recurrent endometrial cancer involve significant toxicities. Imprecise classification of heterogeneous subgroups further complicates treatment decisions and interpretation of clinical trial results. Recent advances in molecular classification are guiding treatment decisions for metastatic or recurrent endometrial cancers. Integrating molecular characteristics with traditional clinicopathology can both reduce overtreatment or undertreatment and help guide the appropriate choice of therapies and effective design of future studies. Here we discuss the treatment of metastatic or recurrent low-grade endometrioid adenocarcinoma of the uterine corpus, which is distinct from high-grade tumors histologically, molecularly, and in treatment response., Competing Interests: Competing interests: The authors disclose the following potential conflicts of interest: IRC: Grants or contracts from any entity: MSD, Roche, BMS, Novartis, AstraZeneca, Merck Sereno; Consulting Fees: Abbvie, Agenus, Advaxis, BMS, PharmaMar, Genmab, Pfizer, AstraZeneca, Roche, GSK, MSD, Deciphera, Mersena, Merck Sereno, Novartis, Amgen, Tesaro and Clovis, Adaptimmun, DAICHI Sankyo, ESAI, Immunogen, Seagen, Blueprint, Takeda, Chugai; Travel Support: Roche, AstraZeneca, MSD, ESAI, GSK; Participation on a Data Safety Monitoring Board or Advisory Board: Athena, ATTEND, AGOOVAR57; MITO25; Leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid: Chair GINECO. DL: Consulting Fees: AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Seagen, Novartis, PharmaMar; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events: AstraZeneca, Clovis Oncology, GSK, MSD, PharmaMar; Payment for expert testimony: Clovis Oncology; Support for attending meetings and/or travel: AstraZeneca, Clovis Oncology, GSK; Participation on a Data Safety Monitoring Board or Advisory Board: Seagen, Immunogen, Genmab, Oncoinvest, Corcept, Sutro, AstraZeneca, GSK; Leadership or fiduciary role in other board, society, committee, or advocacy group, unpaid: GCIG, Member, Board of Directors; Receipt of equipment, materials, drugs, medical writing, gifts, or other services (payments made to institution): Clovis Oncology, GSK, MSD, PharmaMar; Institutional funding for work in clinical trials: AstraZeneca, Clovis Oncology, GSK, MSD, Genmab, PharmaMar, Seagen, Immunogen, Novartis, Roche, Incyte. BJM: Consulting Fees: Acrivon, Adaptimune, Agenus, Akeso Bio, Amgen, Aravive, AstraZeneca, Bayer, Clovis, Easai, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, Heng Rui, ImmunoGen, Karyopharm, Iovance, Laekna, Macrogenics, Merck, Mersana, Myriad, Novartis, Novocure, OncoC4, Panavance, Pieris, Pfizer, Puma, Regeneron, Roche/Genentech, Sorrento, TESARO/GSK, US Oncology Research, VBL, Verastem, Zentalis; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events: AstraZeneca, Easai, Myriad, Roche/Genentech, TESARO/GSK. BS: Consulting Fees: AstraZeneca, Clovis, GSK, Genentech, Lilly, Novartis, Gilead, Seagen, Karyopharm, Addy, Circulogene, GOG Foundation, Merck, Imvax, EQRx, Nuvation; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events: Seagen. The remaining authors declare no conflicts of interest., (© IGCS and ESGO 2023. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Background: Standard treatment of early-stage vulvar cancer is a radical, wide, local excision of the primary tumor and a sentinel lymph node (SLN) procedure for the groins. An inguinofemoral lymphadenectomy is no longer necessary for patients who have a negative SLN or micrometastasis ( ≤ 2 mm). When there is macrometastasis (>2 mm) in the SLN, an inguinofemoral lymphadenectomy is indicated; however, this procedure is associated with major morbidity, such as wound healing, lymphoceles, and lymphedema., Primary Objective: To investigate the safety of replacing inguinofemoral lymphadenectomy by chemoradiation in patients with early-stage vulvar cancer with a macrometastasis (>2 mm) and/or extracapsular extension in the sentinel node., Study Hypothesis: Combination of 56 Gy of radiation to the inguinal site and concurrent cisplatin chemotherapy without completion inguinofemoral lymphadenectomy will be feasible and safe, with low groin recurrence rates., Trial Design: This is a single-arm, prospective phase II treatment trial with stopping rules for unacceptable groin recurrences. Eligible patients will receive 56 Gy of radiation to the involved inguinal site and chemotherapy with concurrent cisplatin., Major Inclusion/exclusion Criteria: Eligible patients undergoing sentinel node procedure will have stage I, unifocal, invasive (>1 mm depth of invasion) squamous cell carcinoma of the vulva with tumor size <4 cm, and no suspicious nodes on imaging. Those eligible for the trial are those with a metastasis >2 mm in the sentinel node and/or extracapsular extension, or more than one sentinel node with micrometastasis ≤2 mm., Primary Endpoint: Groin recurrence rate in the first 2 years after primary treatment., Sample Size: 157 patients with macrometastases in their SLN., Estimated Dates for Completing Accrual and Presenting Results: January 1, 2029., Trial Registration Number: NCT05076942., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Molecular profiling is developing to inform treatment in endometrial cancer. Using real world evidence, we sought to evaluate frontline immune checkpoint inhibitor vs chemotherapy effectiveness in advanced endometrial cancer, stratified by Tumor Mutational Burden (TMB) ≥10 mut/MB and microsatellite instability (MSI)., Methods: Patients with advanced endometrial cancer in the US-based de-identified Flatiron Health-Foundation Medicine Clinico-Genomic Database were included. Data originated from patients treated between January 2011- March 2022 at 280 US clinics. Next-generation sequencing assays were performed via FoundationOne or FoundationOneCDx. Longitudinal clinical data were derived from electronic health records. Immune checkpoint inhibitor treatment included pembrolizumab, dostarlimab, and nivolumab monotherapies. Time to next treatment, time to treatment discontinuation, and overall survival were assessed with the log-rank test and Cox proportional hazard models with adjusted hazard ratios (aHR) for known prognostic factors. We used the Likelihood ratio test to compare biomarker performance., Results: A total of 343 patients received chemotherapy and 28 received immune checkpoint inhibitor monotherapy as frontline treatment. Patients who received monotherapy were more likely to be stage III at diagnosis (immune checkpoint inhibitor: 54.6% vs chemotherapy: 15.0%; p<0.001) and more likely to test MSI-high via next-generation sequencing (immune checkpoint inhibitor: 53.6% vs chemotherapy: 19.2%; p<0.001). In MSI-high cancers, single-agent immune checkpoint inhibitor had a more favorable time to next treatment (aHR: 0.18, p=0.001) and overall survival (aHR 0.29, p=0.045). Additional analyses on 70 unique tumor specimens revealed mismatch repair deficiency (dMMR) via immunohistochemistry and MSI-high via next-generation sequencing concordance (91%), with nominal improvement of MSI over dMMR to predict time to treatment discontinuation (p=0.030), time to next treatment (p=0.032), and overall survival (p=0.22). MSI status was concordant with tumor mutational burden ≥10 in 94.3% of cases., Conclusion: Immune checkpoint inhibitors may have improved efficacy over chemotherapy in frontline treatment for advanced endometrial cancer defined by MSI-high using next-generation sequencing as a nominally better predictor of outcomes than dMMR with immunohistochemistry. This provides the biologic rationale of active phase III trials., Competing Interests: Competing interests: Ryon P. Graf, PhD; Kunal Shah, BS; Natalie Danziger, BS; Douglas I. Lin, MD, PhD, Julia Quintanilha, PhD; Gerald Li, PhD; Julia Elvin, MD, PhD are employees of Foundation Medicine, a wholly owned subsidiary of Roche, and have equity interest in Roche. Roche produces atezolizumab, an ICI. Alessandro D. Santin receives grants from Puma, Immunomedics, Gilead, Synthon, Merck, Boehinger-Ingelheim, Genentech, Eisai, and Tesaro; and also personal fees from Merck, Tesaro, and Eisai. Brian Slomovitz has consultant roles with AstraZeneca, Clovis, GSK, Genentech, Lilly, Merck, Eisai, Genmab, Novartis, Addy, Immunogen. Ramez Eskander reports the following: consulting, advisory, and grant funding from AstraZeneca, Clovis Oncology, Genentech, Merck, Eisai, Genmab, Seagen, Immunogen, Mersana, Myriad. No other authors have conflicts of interest to report., (© IGCS and ESGO 2023. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

This article reviews treatments and targets of interest in endometrial cancer by molecular subtype. The Cancer Genome Atlas (TCGA) classifies four molecular subtypes-mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H); copy number high (CNH)/p53abn; copy number low (CNL)/no specific molecular profile (NSMP); and POLEmut-which are validated and highly prognostic. Treatment consideration by subtype is now recommended. In March and April 2022, respectively, the US Food and Drug Administration (FDA) fully approved and the European Medicines Agency adopted a positive opinion recommending the anti-programmed cell death protein-1 (PD-1) antibody pembrolizumab for advanced/recurrent dMMR/MSI-H endometrial cancer which has progressed on or following a platinum-containing therapy. A second anti-PD-1, dostarlimab, received accelerated approval by the FDA and conditional marketing authorization by the European Medicines Agency in this group. The combination of pembrolizumab/lenvatinib for mismatch repair proficient/microsatellite stable endometrial cancer, including p53abn/CNH and NSMP/CNL, received accelerated FDA approval in conjunction with Australia's Therapeutic Goods Administration and Health Canada in September 2019. The FDA and European Medicines Agency made full recommendations in July 2021 and October 2021. Trastuzumab is National Comprehensive Cancer Network (NCCN) compendium listed for human epidermal growth factor receptor-2-positive serous endometrial cancer, which is primarily within the p53abn/CNH subtype. In addition to hormonal therapy, maintenance therapy with selinexor (exportin-1 inhibitor) showed potential benefit in p53 -wildtype cases in a subset analysis and is being investigated prospectively. Other treatment regimens being evaluated in NSMP/CNL are hormonal combinations with cyclin-dependent kinase 4/6 inhibitors and letrozole. Ongoing trials are evaluating immunotherapy in combination with frontline chemotherapy and other targeted agents. Treatment de-escalation is being evaluated in POLEmut cases given its favorable prognosis with or without adjuvant therapy. Molecular subtyping has important prognostic and therapeutic implications, and should guide patient management and clinical trial design in endometrial cancer, which is a molecularly driven disease., Competing Interests: Competing interests: BS reports consulting fees and payment for educational events outside the submitted work including from AstraZeneca, Clovis, GSK, Genentech, Merck, Eisai, Lilly, Novartis, Genmab, Seagen, Immunogen, Karyopharm, and Seagen. RLC reports grants, consulting fees and payment for educational events outside the submitted work including from AstraZeneca, Clovis, Genelux, Genmab, Merck, Immunogen, Janssen, Roche/Genentech, Agenus, Alkermes, Deciphera, GSK, OncoQuest, Onxerna, Regeneron, Novocure, Abbvie. Compensated advisory boards include VBL Therapeutics. BP reports grants, personal fees and non-financial support outside the submitted work; institutional PI for industry sponsored trials from Tesaro/GSK, AstraZeneca, Merck, Genetech/Roche, Celsion, Karyopharm, Mersana, Takeda Pharmaceuticals, Eisai, and Clovis Oncology. Compensated advisory boards include Tesaro/GSK, AstraZeneca, Mersana, Merck, Clovis Oncology, Eisai, Lily, Toray, Sutro and GOG Foundation., (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Delay in initiating cervical cancer treatment may impact outcomes. In a cohort of patients initially treated by surgery, chemoradiation, chemotherapy, or in a clinical trial, we aim to define factors contributing to prolonged time to treatment initiation., Methods: Data from patients initiating treatment for cervical cancer at a single institution was abstracted. Time to treatment initiation was defined as the interval from the date of cancer diagnosis to the date of treatment initiation. Poisson regression model was used for analysis., Results: Of 274 patients studied, the median time to treatment initiation was 60 days (range 0-551). The median times to initiate surgery (54 days, range 3-96) and chemoradiation (58 days, range 4-187) were not significantly different (relative risk (RR) 1.01, 95% CI 0.98 to 1.04, p=0.54). The shortest median initiation time was for chemotherapy (47 days; RR 1.13, 95% CI 1.08 to 1.19, p<0.0001) and the longest was for clinical trial (62 days; RR 1.18, 95% CI 1.12 to 1.24, p<0.0001). Charity care (RR 1.09, 95% CI 1.05 to 1.14, p<0.0001), Medicare or Medicaid (RR 1.10, 95% CI 1.06 to 1.14, p<0.0001), and self-pay (RR 1.38, 95% CI 1.32 to 1.45, p<0.0001) delayed treatment initiation more than private insurance. Hispanic White women (RR 0.69, 95% CI 0.66 to 0.73, p<0.0001) had a shorter treatment initiation time compared with non-Hispanic White patients, while Afro-Caribbean/Afro-Latina women (RR 0.86, 95% CI 0.81 to 0.90, p<0.0001) and African-American patients (RR 1.13, 95% CI 1.07 to 1.19, p<0.0001) had longer initiation times. Spanish speaking patients did not have a prolonged treatment initiation (RR 0.68, 95% CI 0.66 to 0.71, p<0.0001), though Haitian-Creole speaking patients did (RR 1.07, 95% CI 1.01 to 1.13, p<0.002). Diagnosis at an outside institution delayed treatment initiation time (RR 1.24, 95% CI 1.18 to 1.30, p<0.0001) compared with diagnosis at the cancer center., Conclusion: Factors associated with prolonged time to treatment initiation include treatment modality, insurance status, language spoken, and institution of diagnosis. By closely examining each of these factors, barriers to treatment can be identified and modified to shorten treatment initiation time., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2022. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Asbestos recently returned to the spotlight when Johnson & Johnson halted sales of baby powder due to lawsuits claiming that the talc in baby powder may have been contaminated with asbestos, which has been linked to the risk of ovarian cancer development. Although talc and asbestos have some structural similarities, only asbestos is considered causally associated with ovarian cancer by the WHO's International Agency for Research on Cancer. While it is useful to understand the types and properties of asbestos and its oncologic biology, the history of its association with ovarian cancer is largely based on retrospective observational studies in women working in high asbestos exposure environments. In reviewing the literature, it is critical to understand the distinction between associative risk and causality, and to examine the strength of association in the context of how the diagnosis of ovarian cancer is made and how the disease should be distinguished from a similar appearing but unrelated neoplasm, malignant mesothelioma. Based on contextual misinterpretation of these factors, it is imperative to question the International Agency for Research on Cancer's assertion that asbestos has a clear causal inference to ovarian cancer. This has important clinical implications in the way patients are conceivably counseled and provides motivation to continue research to improve the understanding of the association between asbestos and ovarian cancer., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Low grade serous ovarian carcinoma is a rare subtype of ovarian cancer with an indolent and chemorefractory course. As such, treatment strategies among practitioners are not uniformly known. The primary objective of this study was to identify differences in practice patterns among physicians who treat low grade serous carcinoma., Methods Materials: A de novo survey was distributed to members of the Society of Gynecologic Oncology. Questions about demographics, management of primary and recurrent disease, and use of consolidation therapy were included. Statistical analyses were performed using χ 2 and Fisher's exact tests., Results: 194 gynecologic oncologists completed the survey. Approximately two-thirds of respondents practiced in a university based setting and treated a high volume of ovarian cancers, including low grade serous carcinoma. 82% recommended somatic testing during treatment and 84% routinely sent patients for genetic counseling. Treatment preferences for primary disease varied by debulking status. 48% of practitioners used hormone antagonism as consolidation after primary treatment. Secondary cytoreduction was preferred for patients with platinum sensitive recurrence and a long disease free interval following primary treatment (P<0.001). Hormone antagonism was the preferred treatment for the first platinum resistant recurrence (54%), while a BRAF inhibitor was the preferred agent in platinum resistant recurrence in the presence of a known BRAF mutation (56%)., Conclusions: There was significant variation in the preferred management of low grade serous carcinoma among practitioners. Further efforts to improve knowledge of this disease, identify optimal treatment modalities, and provide guidelines for management should be encouraged., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Cyclins D1 and D3 play key roles in cell cycle progression. The downregulation of cyclin D3 was associated with phosphatase and tensin homolog deleted on chromosome ten-(PTEN)-induced cell cycle arrest. We attempted to determine whether cyclin D1 and D3 overexpression is correlated with PTEN inactivation in endometrioid endometrial cancer (EEC). The expression of PTEN, cyclin D1, and cyclin D3 were determined by immunohistochemical analysis in 105 EEC specimens. Forty-three percent of the EEC demonstrated loss of PTEN expression. Cyclin D3 was overexpressed in only 18% of the EEC specimens and was not associated with tumor grade. Cyclin D1 was overexpressed in 64% of the specimens and was more common in moderate or high-grade tumors (P = 0.002 and P = 0.02, respectively). The overexpression of cyclin D3 was not correlated with loss of PTEN in the EEC. The overexpression of cyclin D1 was much higher in grade 1 tumors with negative PTEN than tumors with positive PTEN expression (67% vs 26%). The overexpression of cyclin D3 was neither frequent nor correlated with the loss of PTEN expression. The overexpression of cyclin D1 was higher in the low-grade tumors with negative PTEN expression than tumors with positive PTEN expression. Overexpression of cyclin D1 is frequent in moderate or high-grade EECs and likely results from multiple mechanisms.

The purpose of this study was to evaluate overall survival (OS) and determine prognostic subclassifications for stage IIIA endometrial cancer. Stage IIIA endometrial cancer patients treated at M.D. Anderson Cancer Center from 1989 to 2002 were reviewed. Clinical information was obtained from the medical record. Cox regression analyses were performed to evaluate the association of pathologic criteria and OS. Patients were divided into four groups based on this analysis: E1, endometrioid/pelvic cytology only; E2, endometrioid/adnexa +/- serosal spread; NE1, nonendometrioid/pelvic cytology only; and NE2, nonendometrioid/adenexa +/- serosal spread. Forty-nine patients were identified. By multivariate analysis, histology and extent of disease were the only factors associated with OS. Five-year OS in the four subgroups based on histology and extent of disease were: E1, 79%, E2, 65%, NE1, 64%, and NE2, 13%. Histologic subtype and extent of pelvic disease are the only prognostic factors associated with OS. Patients with endometrioid tumors and extent of pelvic disease limited to positive cytology had a favorable outcome, with or without adjuvant therapy. Future prospective clinical trials should consider subclassifying patients with stage IIIA disease to better evaluate the role of adjuvant therapy.