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Introduction: Early reports of PD-1 inhibition in ovarian clear cell carcinomas (OCCC) demonstrate promising response. We evaluated the combination of pembrolizumab and IDO-1 inhibitor epacadostat in patients with recurrent OCCC., Methods: This single arm, two-stage, phase 2 trial included those with measurable disease and 1-3 prior regimens. Patients received intravenous pembrolizumab 200 mg every 3 weeks and oral epacadostat 100 mg twice a day. Primary endpoint was overall response rate (ORR), secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS). The study was powered to detect an absolute 25% increase in response (15% to 40%)., Results: Between September 28, 2018 and April 10, 2019, 14 patients enrolled at first stage. Rate of accrual was 2.3 patients per month. Median age was 65 years (44-89), 10 (71.4%) had ≥2 prior regimens. ORR was 21% (95% CI 5-51%) within 7 months of study entry with 3 partial responses, and 4 had stable disease (disease control rate 50%). Median PFS was 4.8 months (95% CI: 1.9-9.6), OS 18.9 months (95% CI: 1.9-NR). Most common grade ≥ 3 adverse events were electrolyte abnormalities and gastrointestinal pain, nausea, vomiting, bowel obstruction. In July 2019, the study reached the pre-specified criteria to re-open to second stage; however, the study closed prematurely in February 2021 due to insufficient drug supply., Conclusions: Pembrolizumab and epacadostat demonstrated an ORR of 21% in this small cohort of recurrent OCCC. The rapid rate of accrual highlights the enthusiasm and need for therapeutic studies in patients with OCCC., Competing Interests: Declaration of competing interest Dr. Lilian Gien received consulting fees from Merck – Advisor Board – October 2021. She also received Speaker Honorarium – January 2021 – from Merck. Dr. Danielle Enserro received funding from NCI for Cooperative Group/NCTN Grant Funding for all aspects of this trial including travel to Group meetings, trial design, statistical design and analysis, study monitoring, writing/editing of abstracts/manuscripts, etc. Dr. Matthew S. Block received grants or contracts from Merck – drug only contract for investigator-sponsored trial; Regeneron, Sorrento, Transgene, TILT Biotherapeutics, Alkermes, Bristol-Myers Squibb, Genentech, nFerence, Pharmacyclics and Viewpoint Molecular Therapeutics – institutional payment for clinical trial. He also has a patent filed for Dendritic Cell Based Vaccines Combined with Penbrolizumab for the Treatment of Advanced Ovarian Cancer – patent filed; author has waived rights to personal financial gain. He has participated on a Data Safety Monitoring Board or Advisory Board from TILT Biotherapeutics, Sorrento, and Viewpoint Molecular Therapeutics – no payment received. Dr. Linda Duska has multiple grants from sponsors for clinical trials. These grants go to her institution and not to her. These include, but are not limited to: (research funding (to institution) for investigator initiated trials for Merck, clinical trial grants (to institution) from Genentech/Roche, AbbVie/(GOG 3005), Acrivon, Advaxis, Aduro BioTech, Alkermes, Blueprint, Constellation, Eisai, GlaxoSmithKlein/Novartis, Immunogen, Inovio, Iovance, Karyopharm, KSQ Therapeutics, Lycera, Merck, Morab, MorphoTek, Naveris, Nurix, OncoQuest, Pfizer, Syndax, Tesaro, and Zentalis. She has Royalties or licenses (all up to date) with Wiley and ASCO (Editor of ASCO Connection). She received consulting fees from Regeneron, Aadi Bioscience and Merck for serving on Scientific Advisory Boards. She received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Advance Medical, CEA Group and Clinical Care Options (CME). She has participated on a Data Safety Monitoring Board or Advisory Board for Innovio DSMB (to institution) and Aegenus DSMB (to institution). She served as Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid as Secretary Treasurer for SGO (unpaid) and Editorial Board, British Journal of OB/GYN. Dr. Andrea E. Wahner-Hendrickson received Grants or contracts from TORL Therapeutics (funding to institution for clinical trial, OXCIA (advisory board – unpaid), Prolynx (funding to institution for clinical trial and Mayo Ovarian SPORE (P50 CA1363939). She participated on a Data Safety Monitoring Board or Advisory Board for OXCIA (unpaid). She also served in a Leadership or fiduciary role in other board, society, committee or advocacy group – MOCA (unpaid). Dr. Premal H. Thaker received grants to his institution from Merck and GlaxoSmithKline. She received consulting fees from Immunon. She also participated on a Data Safety Monitoring Board or Advisory Board with AstraZeneca, Clovis Oncology, GlaxoSmithKline, Seagen, Agenus, Immunon, Immuogen, Mersana, Novocure, R-Pharm, Zentalis, Aadi Pharmaceuticals, Merck, Caris Iovance and Verastem. She also has stock or stock options with Immunon. Dr. Floor Backes received grants or contracts from Merck, Eisai, ImmunoGen, Clovis, Beigene, Natera, Tempus and AstraZeneca (research grants paid to the institution). Royalties or licenses from UptoDate (personal fees). She also received consulting fees from Agenus, Merck, Clovis, Immunogen, Eisai, AstraZeneca, GlaxoSmithKline, Myriad, BioNTech and Daiichi Sankyo (Advisory boards – personal fees). She received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Clinical Educational Concepts, Clinical Care Options, Medscape/WebMD, Med Learngin, 13Health, CMR Institute, Global Learning Initiative/Prova, OncLive, Targeted Oncology and Research To Practice (CME lectures – personal fees). She received support for attending meetings and/or travel from GlaxoSmithKline. She participated on a Data Safety Monitoring Board – see consulting fees. She served in a Leadership or fiduciary role on other board, society, committee or advocacy group, paid or unpaid from Society of Gynecologic Oncology (Board member – unpaid), NRG Oncology Developmental Therapeutics Committee – Co-Chair and IGCS Education360 – Co-Chair. Dr. Carolyn Y. Muller received a grant to her institution from New Mexico Minority Underserved NCORP to support enrollment to all NCI NCTN trials. She has a contract to her institution to enroll to GOG Partners trials from GOG Partners Foundation (Segan, GSK, Mersana, Alkemes, Merck, Verastem, Immunogen, etc). She received contracts to her institution for enrollment to specific clinical trials from Linneus Therapeutics. She serves as Chair, Board of Directors of the New Mexico Cancer Research Alliance (unpaid position that manages an affiliate consortium to provide access to clinical trials across the states many health systems). Dr. Paul DiSilvestro serves on the NRG Oncology Board of Directors in a leadership or fiduciary role. Dr. David M. Gershenson's institution received a grant from Novartis. He has royalties or licenses from Elsevier and UpToDate. He received consulting fees to himself from Verastem. He received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Yale University and University of Washington. He serves in a Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid from International Consortium for Low Grade Serous Ovarian Cancer. He has stock in Bristol Myers Squibb, Johnson & Johnson and Proctor & Gamble. He has other financial or non-financial interests himself in Audi AB, Verastem AB, Springworks AB and Onconova AB. Dr. Kathleen N. Moore has grants/contracts from Clovis Oncology Pharmaceutical, Eli Lilly and Company, Genentech, GSK plc Pharmaceutical, Merck, PTC Therapeutics Pharmaceuticals, Verastem Oncology and Biotech. She received support for attending meetings and/or travel from Duality, GSK and Regeneron. She participates on a Data Safety Monitoring Board or Advisory Board for AstraZeneca, Aravive, Aadi Bioscience, Alkermes, Blueprint Medicines, Caris, Clovis Oncology Pharmaceutical, Duality, Eisai Pharmaceutical, EMD Serono Inc., Eli Lilly and Company, Genentech Biotechology, GSK plc Pharmaceutical, ImmunoGen Biotechnology, InxMed, I-MAB Biotech, Iovance, Jiangsu Hengrui Medicine Pharmaceutical, Merck, Mereo BioPharma Group, Mersana Therapeutics Inc., Myriad Genetics, Novartis Pharmaceuticals, Onconova Therapeutics Inc., OncXerna Therapeutics, Inc., Regeneron, VBL, and Verastem Oncology. She serves in a leadership or fiduciary role for GOG Partners and ASCO. Dr. Carol Aghajanian received Clinical Trial funding to her institution (MSK) from: Abbvie – MSKPI – GOG 3005; AstraZeneca – MSK PI, SOLO1/GOG 3004; National Coordinating Investigator and MSK PI, DO81RC00001; ENGOT-ov46; AGO-OVAR 23; GOG-3025; Clovis – MSK PI, ARIEL 2 &3; Genentech/Roche – MSK PI, GOG3015 (IMagyn050). She also participates on an Advisory Board for Blueprint Medicine – Advisory Board 6/30/21 (no consulting fee); Mrck – Global Cervical and Ovaian Cancer Virtual Advisory Board 7/10/23 (no consulting fee) and AstraZeneca – AZ Evolve dmc 4/26/23-ongoing, She also serves on the GOG Foundation, Board of Directors (unpaid, occasional travel cost reimbursement to attend meetings) and NRG Oncology Board of Directors (unpaid)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Gynecologic cancers are traditionally managed according to their presumed site of origin, without regard to the underlying histologic subtype. Clear cell histology is associated with chemotherapy refractoriness and poor survival. Mutations in SWI/SNF chromatin remodeling complex member ARID1A, which encodes for BAF250a protein, are common in clear cell and endometriosis-associated endometrioid carcinomas. High-throughput cell-based drug screening predicted activity of dasatinib, a tyrosine kinase inhibitor, in ARID1A-mutant clear cell carcinoma., Methods: We conducted a phase 2 clinical trial of dasatinib 140 mg once daily by mouth in patients with recurrent or persistent ovarian and endometrial clear cell carcinoma. Patients with measurable disease were enrolled and then assigned to biomarker-defined populations based on BAF250a immunohistochemistry. The translational endpoints included broad next-generation sequencing to assess concordance of protein expression and treatment outcomes., Results: Twenty-eight patients, 15 of whom had tumors with retained BAF250a and 13 with loss of BAF250a were evaluable for treatment response and safety. The most common grade 3 adverse events were anemia, fatigue, dyspnea, hyponatremia, pleural effusion, and vomiting. One patient had a partial response, eight (28%) had stable disease, and 15 (53.6%) had disease progression. Twenty-three patients had next-generation sequencing results; 13 had a pathogenic ARID1A alteration. PIK3CA mutations were more prevalent in ARID1A-mutant tumors, while TP53 mutations were more prevalent in ARID1A wild-type tumors., Conclusions: Dasatinib was not an effective single-agent treatment for recurrent or persistent ovarian and endometrial clear cell carcinoma. Studies are urgently needed for this rare gynecologic subtype., Competing Interests: Conflicts of interest Roisin O'Cearbhaill - reports personal fees from once off advisory boards from Tesaro/GSK, Regeneron, Seattle Genetics, Fresenius Kabi, Immunogen, R-Pharm, Miltenyi, 2seventybio and Bayer, outside the submitted work; received honoraria for lectures from Gynecologic Oncology Foundation, Curio, PER/MJH, SITC, Gynecologic Oncology Canada and support to attend meetings from Hitech Health, Gathering Around Cancer, Ireland, GOG Foundation and SGO. Non-compensated steering committee member for the PRIMA, Moonstone (Tesaro/GSK) and DUO-O (AstraZeneca) studies and non-compensated advisor for Carina Biotech, Acrivon, Link Therapeutics and Transgene. NRG representative for the ComboMATCH and iMATCH studies. Her institute receives funding for clinical research from Bayer/Celgene/Juno, Tesaro/GSK, Merck, Ludwig Cancer Institute, Abbvie/StemCentrx, Regeneron, TCR2 Therapeutics, Atara Biotherapeutics, MarkerTherapeutics, Syndax Pharmaceuticals, Genmab/Seagen Therapeutics, Sellas Therapeutics, Genentech, Kite Pharma, Gynecologic Oncology Foundation, Acrivon and Lyell Immunopharma. Robert Soslow is a co-editor for the journal Modern Pathology. Dmitriy Zamarin has grants/contracts from AstraZeneca, Merck, Plexxikon, Synthekine and Genentech. He has patient licensng fees through Merck. He has received consulting fees from AstraZeneca, Synthekine, Astellas, Tessa Therapeutics, Memgen, Celldex, Crown Biosciences, Hookipa, Kalivir, Xencor and GSK. Patents planned, issued or pending include Merck for use of oncoltic NDV for cancer therapy. He also has stock options for Accurius, Immunos and Calidi Biotherapeutics. Kathleen Moore's institution receives research funding from PTC Therapeutics, Lilly, Clovis, Genentech, GSK and Verastem. Her Royalties/licenses are up to date. She received consulting fees from AstraZeneca, Aravive, Alkemeres, Aadi, Blueprint pharma, Clovis, Caris Eisai, GSK, Genentech/Roche, Hengrui, Immunogen, Inxmed, Imab, Iovance, Lilly, Mereo, Mersana, Merck, Myriad, Novartis, Novocure, Pannavance, OncXerna, Onconova, Tarveda, VBL Therapeutics and Verastem. She has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from PRIME, RTP, Medscape, Great Debates and Updates. She has received support for attending meetings and/or travel from AstraZeneca. She has a Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid through GOG P Associate Director. Mark Shahin received grants or contracts from GSK, AstraZeneca and Merck. He also received consulting fees from GSK, AstraZeneca and Immunogen. He received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from GSK, AstraZeneca, Merck, Eisai, Immunogen and SeaGen. He has a leadership or fiduciary role with UniteForHer. Premal Thaker's institution received grants/contracts from Merck and GSK. He has received consulting fees from Novartis for endometrial cancer, Merck, AstraZeneca, Clovis Oncology, GSK, Novocure, R-Pharm, Immunon, Zentalis and Aadi Bioscience. Andrea E. Wahner-Hendrickson has an NCI grant (P50 CA 136393) for Mayo Ovarian Cancer SORE (Co-project leader), TORL – Site PI Clinical Trial and Prolynx – IIT. She ha received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from George Washington University for Medical Oncology Board Review (CME) – ovary and uterine. She participates on a Data Safety Monitoring Board or Advisory Board at Mayo Clinic DSMB NCI CIRB (early emphasis). She has unpaid Leadership or fiduciary roles in other board, society, committee or advocacy group with Oxcia Advisory Board and MN ovarian cancer advisory board. Carol Aghajanian received clinical trial funding to institution (MSK): Abbvie – MSK PI, GOG 3005, AstraZeneca – MSK PI, SOLO1/GOG 3004; National Coordinating Investigator & MSK PI, DO81RC00001; ENGOT – ov46; AGO-OVAR 23; GOG-3025; Clovis – MSK PI, ARIEL 2 & 3; Genentech/Roche – MSI PI, GOG 3015 (Imagyn050). She has received consulting fees from Abbvie – Advisory Board 5/8/20; Roche/Genentech – Advisory Board 8/21/20; Eisai/Merck – Advisory Board 9/12/20; AstraZeneca/Merck – Advisory Boards 9/30/20 & 10/14/20; and Repare Therapeutics – Advisory Board 10/15/20. She has participated on an Advisory Board – 6/30/21 (no consulting fee) for Blueprint Medicine. She also served as Leadership or fiduciary role in other board, society, committee or advocacy group for GOG Foundation, Board of Directors (travel cost reimbursement for attending meetings) and NRG Oncology Board of Directors (unpaid). Austin Miller, Heather Lankes, Deborah Delair, Sheila Segura, Shweta S. Chavan, Robert DeBernardo, and John Moroney have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Our objectives were to determine the incidence, timing, and risk factors for venous thromboembolisms (VTEs) in patients with advanced stage epithelial ovarian cancer (EOC) who received neoadjuvant chemotherapy (NACT). We explored the utilization of direct-acting oral anticoagulants (DOACs) for VTE treatment., Methods: This retrospective cohort study included patients with advanced stage EOC receiving NACT followed by interval cytoreductive surgery (ICS) at a single institution. Risk factors were compared between patients with versus without VTE between EOC diagnosis and 180 days after ICS. Bleeding complications were compared between patient who received a DOAC versus non-DOAC., Results: VTE cases occurred amongst 33 of the 154 (21.4%) patients with 4 (2.6%) concurrent with EOC diagnosis, 9 (5.8%) between EOC diagnosis and NACT start, 13 (8.4%) between NACT start and ICS, and 7 (4.5%) within 180 days after ICS. There were no statistically significant differences in risk factors assessed (age, body mass index, functional status, histology, Khorana score, and smoking history) between patients with versus without VTE. Eleven patients (33.3%) received a DOAC for VTE treatment. There were no significant differences in number of intraoperative blood transfusions (p = 0.38), blood loss (p = 0.95), or bleeding complications (p = 0.53) between patients treated with a DOAC versus a non-DOAC., Conclusion: There is a high incidence of VTE events (21.4%) in patients with advanced stage EOC undergoing NACT. Two-thirds of the VTEs may have been prevented with thromboprophylaxis as they occurred between EOC diagnosis and ICS. These data support consideration of thromboprophylaxis in all patients with advanced stage EOC undergoing NACT., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To determine the effects of using National Comprehensive Cancer Network (NCCN) guidelines to estimate renal function on carboplatin dosing and explore adverse effects associated with a more accurate estimation of lower creatinine clearance (CrCl)., Methods: Retrospective data were obtained for 3830 of 4312 patients treated on GOG182 (NCT00011986)-a phase III trial of platinum-based chemotherapy for advanced-stage ovarian cancer. Carboplatin dose per patient on GOG182 was determined using the Jelliffe formula. We recalculated CrCl to determine dosing using Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault (with/without NCCN recommended modifications) formulas. Associations between baseline CrCl and toxicity were described using the area under the receiver operating characteristic curve (AUC). Sensitivity and positive predictive values described the model's ability to discriminate between subjects with/without the adverse event., Results: AUC statistics (range, 0.52-0.64) showed log(CrCl Jelliffe ) was not a good predictor of grade ≥3 adverse events (anemia, thrombocytopenia, febrile neutropenia, auditory, renal, metabolic, neurologic). Of 3830 patients, 628 (16%) had CrCl <60 mL/min. Positive predictive values for adverse events ranged from 1.8%-15%. Using the Cockcroft-Gault, Cockcroft-Gault with NCCN modifications, and MDRD (instead of Jelliffe) formulas to estimate renal function resulted in a >10% decrease in carboplatin dosing in 16%, 32%, and 5.2% of patients, respectively, and a >10% increase in carboplatin dosing in 41%, 9.6% and 12% of patients, respectively., Conclusion: The formula used to estimate CrCl affects carboplatin dosing. Estimated CrCl <60 mL/min (by Jelliffe) did not accurately predict adverse events. Efforts continue to better predict renal function. Endorsing National Cancer Institute initiatives to broaden study eligibility, our data do not support a minimum threshold CrCl <60 mL/min as an exclusion criterion from clinical trials., Competing Interests: Declaration of Competing Interest Dr. O'Cearbhaill reports support for this study from NCI/NIH P30 CA008748 and grants to Institution from Bayer/Celgene/Juno, Tesaro/GSK, Merck, Ludwig Cancer Institute, AbbVie/Stemkens, Regeneron, TCR2 Therapeutics, Atara Biotherapeutics, Marker Therapeutics, Syndax Pharmaceuticals, Genmab/Seagen Therapeutics, Genentech, Kite Pharma, Acrivon and Gynecologic Oncology Foundation. Outside of the submitted work, Dr. O'Cearbhaill reports honoraria from GSK, Bayer, Regeneron, SeaGen, Fresenius Kabi, Immunogen, MJH Life Sciences and Curio. Dr. O'Cearbhaill reports receiving support to attend meetings and/or travel from Hitech Health, Gathering Around Cancer, Ireland, GOG Foundation and SGO. Dr. O'Cearbhaill participated on Data Safety Monitoring Board or Advisory Board for each of the following: AstraZeneca (DUO-0), GSK (moonstone, Prima), Acrivon, Carina Biotech, Link therapeutics, Tesaro/GSK, Regeneron, Seattle Genetics/Seagen, Immunogen, Bayer, R-Pharm, 2seventybio, Miltenyi and Fresenius Kabi. Dr. O'Cearbhaill also served as Vice-chair for the CPC, SGO as well a Chair, Developmental Therapeutics Committee for NRG Oncology. Dr. Aghajanian received research grants from AbbVie, Clovis, Genentech and Astra Zeneca and served on advisory boards for AbbVie, AstraZeneca/Merck, Eisai/Merck, Mersana Therapeutics, Repare Therapeutics and Roche/Genentech and received consulting fees for serving. Dr. Aghajanian served on the Blueprint Medicine Advisory Board (uncompensated). Dr. Aghajanian also serves on the GOG Foundation, Board of Directors (travel cost reimbursement for attending meetings) as well as the NRG Oncology Board of Directors (unpaid). Dr. Floor Backes wishes to report research grants from Immunogen, Clovis, Merck, Eisai, Natera and Beigene. Dr. Backes reports receiving consulting fees received from Eisai, Merck, Agenus, AstraZeneca, GlaxoSmithKline; Myriad, Clovis Oncology and Immunogen. Dr. Backes received honoraria for serving on advisory boards from Medlearning Group, CEC Oncology, OncLive, i3Health, and Medscape. Dr. Backes serves as Co-Chair of the NRG Oncology Developmental Therapeutics. Dr. Backes is a member of the Uterine Corpus Committee as well as a NCCN Ovary member and serves as an SGO Board Member. Dr. Michael Bookman reports payment to his Institution from Immunogen Data Monitoring Committee (unrelated to this project). Dr. David Cohn reports receiving honoraria from UpToDate as an Author as well as receiving payment for his role with Elsevier, Gynecologic Oncology as an Editor-in-Chief. Dr. Michael Friedlander reports that personally receiving consulting fees from AstraZeneca, Novartis, GSK and Incyclix (Nil). Dr. Friedlander also reports receiving honoraria from AstraZeneca and GSK and also received travel funding from AstraZeneca. Dr. Friedlander reports participating on Data Safety Monitoring Board/Advisory Board for AGITG IDSMB and ENDO-3. Dr. Friedlander reports that his Institution received grants from AstraZeneca, Beigene and Novartis. Dr. David Gershenson reports support from NRG Oncology with regard to this Study. Dr. Gershenson also acknowledges grants to his Institution from Novartis, GOG Foundation, and the NCI. Dr. Gershenson personally received royalties from Elsevier and UpToDate and consulting fees from Genentech (uncompensated) and Verastem. Dr. Gershenson received honoraria from University of Washington OB/GYN Grand Rounds and Yale University OB/GYN Grand Rounds and participating in a data safety monitoring/advisory board for Onconova, Aadi and Springworks. Dr. Gershenson also served on the International Consortium for Low-Grade Serous Ovarian Cancer and NCCN Ovarian Cancer Panel (uncompensated). Dr. Gershenson also wishes to disclose having stock in managed accounts for Bristol Myers Squibb, Johnson & Johnson and Procter & Gamble. Dr. Michael Goodheart reports receiving consulting fees from GlasoSmithKlein GSK/Tesaro, Merck, AstraZeneca, Clovis Oncology, SeaGen and Eisai. Dr. Angeles Alvarez Secord reports clinical trial grants received from the following: AbbVie, Aravive, AstraZeneca, BoehringerIngelheim, Clovis, Eisai, Ellipses, I-MAB Biopharma, Immunogen, Merck, Oncoquest/Canaria Bio, Seagen Inc., TapImmune, Tesaro/GSK, VBL Therapeutics. Dr. Secord also wishes to report receiving clinical trial grant/translational research grant from Roche/Genentech as well as Consulting fee from Myriad. Dr. Secord also received support for attending meetings/travel from GSK, GOG Foundation and NRG. Dr. Secord also served on the Clinical Trial Steering Committees for Aravive, Genentech/Roche, VBL Therapeutics and Oncoquest/Canaria Bio without compensation. Dr. Secord personally received compensation from GOG Foundation and NRG Oncology paid compensation to Institution. Dr. Secord also served in Leadership roles for Society of Gynecologic Oncology and American Association of Obstetrics and Gynecology Foundation (uncompensated). Dr. Judith Smith received honoraria for Speaking at the HOPA Annual Meeting 2016 – Harmonization of Carboplatin Dosing, Dr. Smith serves as Chair on the NRG Oncology Pharmacy Subcommittee. Dr. Tewari also reports receiving honoraria from Eisai, AstraZeneca, Clovis, GSK/Tesaro, Merck and Seagen/Genmab. Dr. Krishnansu Tewari reports receiving consulting fees from Regeneron, Eisai, AstraZeneca, Clovis, GSK/Tesaro, Merck, Seagen/Genmab. Dr. Andrea Wahner Hendrickson reports receiving Clinical Trial support from Prolynx and Site PI Clinical Trial Support from both Amgen and TORL Biotherapeutics. Dr. Wahner Hendrickson reports serving on Oxcia Advisory Board (uncompensated). Dr. Wahner Hendrickson reports serving on an Advisory Board for the Mayo Clinic Data Safety Monitoring Board (uncompensated). Dr. Wahner Hendrickson also served on the NCCN Ovarian Cancer Committee (uncompensated). Dr. Robert Wenham reports personal and institutional grants received from Merck and Ovation Diagnostics. Dr. Wenham reports receiving consulting fees from Merck, Legend Biotech, Genentech, Ovation Diagnostics, GSK/Tesaro, Clovis, AstraZeneca, AbbVie, Legend Biotech, Regeneron, Seagen, Sonic Biotherapeutics, Shattuck Labs, Novacure, Eisai and Immunogen. Dr. Wenham also reports receiving Institutional Clinical Trial Fees from AbbVie, AstraZeneca, Regeneron and Eisai. Dr. Wenham reports serving on Advisory Board for Seagen and GSK/Tesaro. Dr. Wenham would like to disclose personally owning stock in Ovation Diagnostics. Dr. Peter Argenta, Dr. Heidi Gray, Dr. Roger Lee, Dr. Stuart Lichtman, Dr. Austin Miller, Dr. David Mutch, Dr. Aaron Praiss, Dr. Paul Sabbatini and Dr. Linda Van Le have no potential conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To assess the effect of age on overall survival (OS) in women with ovarian cancer receiving chemotherapy. Secondary objectives were to describe the effect of age on treatment compliance, toxicities, progression free survival (PFS), time from surgery to chemotherapy, and rates of optimal cytoreduction., Methods: Women enrolled in GOG 0182-ICON5 with stage III or IV epithelial ovarian cancer (EOC) who underwent surgery and chemotherapy between 2001 and 2004 were included. Patients were divided into ages <70 and ≥ 70 years. Baseline characteristics, treatment compliance, toxicities, and clinical outcomes were compared., Results: We included a total of 3686 patients, with 620 patients (16.8%) ≥ 70 years. OS was 37.2 months in older compared to 45.0 months in younger patients (HR 1.21, 95% CI, 1.09-1.34, p < 0.001). Older patients had an increased risk of cancer-specific-death (HR 1.16, 95% CI, 1.04-1.29) as well as non-cancer related deaths (HR 2.78, 95% CI, 2.00-3.87). Median PFS was 15.1 months in older compared to 16.0 months in younger patients (HR 1.10, 95% CI, 1.00-1.20, p = 0.056). In the carboplatin/paclitaxel arm, older patients were just as likely to complete therapy and more likely to develop grade ≥ 2 peripheral neuropathy (35.7 vs 19.7%, p < 0.001). Risk of other toxicities remained equal between groups., Conclusions: In women with advanced EOC receiving chemotherapy, age ≥ 70 was associated with shorter OS and cancer specific survival. Older patients receiving carboplatin and paclitaxel reported higher rates of grade ≥ 2 neuropathy but were not more likely to suffer from other chemotherapy related toxicities. Clintrials.gov: NCT00011986., Competing Interests: Declaration of Competing Interest Each coauthor must complete an icmje form so that this page can be completed., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Age and ethnicity are among several factors that influence overall survival (OS) in ovarian cancer. The study objective was to determine whether ethnicity and age were of prognostic significance in women enrolled in a clinical trial evaluating the addition of bevacizumab to front-line therapy., Methods: Women with advanced stage ovarian, primary peritoneal, or fallopian tube cancer were enrolled in a phase III clinical trial. All women had surgical staging and received adjuvant chemotherapy with one of three regimens. Cox proportional hazards models were used to evaluate the relationship between OS with age and race/ethnicity among the study participants., Results: One-thousand-eight-hundred-seventy-three women were enrolled in the study. There were 280 minority women and 328 women over the age of 70. Women age 70 and older had a 34% increase risk for death when compared to women under 60 (HR = 1.34; 95% CI 1.16-1.54). Non-Hispanic Black women had a 54% decreased risk of death with the addition of maintenance bevacizumab (HR = 0.46, 95% CI:0.26-0.83). Women of Asian descent had more hematologic grade 3 or greater adverse events and a 27% decrease risk of death when compared to non-Hispanic Whites (HR = 0.73; 95% CI: 0.59-0.90)., Conclusions: Non-Hispanic Black women showed a decreased risk of death with the addition of bevacizumab and patients of Asian ancestry had a lower death rate than all other minority groups, but despite these clinically meaningful improvements there was no statistically significant difference in OS among the groups., (Copyright © 2021. Published by Elsevier Inc.)

Objective: Poly(ADP-ribose) polymerase (PARP) inhibitors have shown substantial activity in homologous recombination- (HR-) deficient ovarian cancer and are undergoing testing in other HR-deficient tumors. For reasons that are incompletely understood, not all patients with HR-deficient cancers respond to these agents. Preclinical studies have demonstrated that changes in alternative DNA repair pathways affect PARP inhibitor (PARPi) sensitivity in ovarian cancer models. This has not previously been assessed in the clinical setting., Methods: Clonogenic and plasmid-based HR repair assays were performed to compare BRCA1-mutant COV362 ovarian cancer cells with or without 53BP1 gene deletion. Archival biopsies from ovarian cancer patients in the phase I, open-label clinical trial of PARPi ABT-767 were stained for PARP1, RAD51, 53BP1 and multiple components of the nonhomologous end-joining (NHEJ) DNA repair pathway. Modified histochemistry- (H-) scores were determined for each repair protein in each sample. HRD score was determined from tumor DNA., Results: 53BP1 deletion increased HR in BRCA1-mutant COV362 cells and decreased PARPi sensitivity in vitro. In 36 women with relapsed ovarian cancer, responses to the PARPi ABT-767 were observed exclusively in cancers with HR deficiency. In this subset, 7 of 18 patients (39%) had objective responses. The actual HRD score did not further correlate with change from baseline tumor volume (r = 0.050; p = 0.87). However, in the HR-deficient subset, decreased 53BP1 H-score was associated with decreased antitumor efficacy of ABT-767 (r = -0.69, p = 0.004)., Conclusion: Differences in complementary repair pathways, particularly 53BP1, correlate with PARPi response of HR-deficient ovarian cancers., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: We report the results of a phase 2 clinical trial of the combination of everolimus and letrozole in patients with relapsed estrogen receptor-positive high-grade ovarian cancer. The trial's primary endpoint was the proportion of patients alive and progression-free after 12weeks of therapy with the combination of everolimus and letrozole. A 12-week PFS of 45% or greater was considered a positive result. The feasibility of generating patient-derived xenograft (PDX) models from biopsy specimens was also evaluated., Methods: Eligibility criteria included relapsed estrogen receptor-positive ovarian, fallopian tube or primary peritoneal carcinomas with measurable disease, not previously treated with everolimus or AIs. Both platinum-resistant and sensitive tumors were included. Xenografts were created from image-guided tumor biopsies at baseline. Patients received oral everolimus 10mg daily and letrozole 2.5mg daily., Results: Twenty patients were enrolled, 19 were evaluable. Nine out of 19 were alive, progression-free, and still on treatment at the 12week evaluation time-point (12-week PFS of 47%) with a median PFS of 3.9months (95% CI: 2.8-11.0). The median overall survival was 13.0months. Twelve patients (63%) experienced at least one grade 3 or worse adverse events. PDX tumor engraftment was feasible in the majority of patients (9 out of 17, 52.9%)., Conclusions: The combination of everolimus and letrozole is associated with a promising 47% 12-week PFS rate in patients with ER-positive relapsed high-grade ovarian cancer with acceptable toxicity. PDX tumor models can be generated from biopsies of ovarian tumors., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: Epithelial ovarian cancer (EOC) is an aggressive disease in which first line therapy consists of a surgical staging/debulking procedure and platinum based chemotherapy. There is significant interest in clinically applicable, easy to use prognostic tools to estimate risk of recurrence and overall survival. In this study we used a large prospectively collected cohort of women with EOC to validate currently published models and assess prognostic variables., Methods: Women with invasive ovarian, peritoneal, or fallopian tube cancer diagnosed between 2000 and 2011 and prospectively enrolled into the Mayo Clinic Ovarian Cancer registry were identified. Demographics and known prognostic markers as well as epidemiologic exposure variables were abstracted from the medical record and collected via questionnaire. Six previously published models of overall and recurrence-free survival were assessed for external validity. In addition, predictors of outcome were assessed in our dataset., Results: Previously published models validated with a range of c-statistics (0.587-0.827), though application of models containing variables which are not part of routine practice were somewhat limited by missing data; utilization of all applicable models and comparison of results are suggested. Examination of prognostic variables identified only the presence of ascites and ASA score to be independent predictors of prognosis in our dataset, albeit with marginal gain in prognostic information, after accounting for stage and debulking., Conclusions: Existing prognostic models for newly diagnosed EOC showed acceptable calibration in our cohort for clinical application. However, modeling of prospective variables in our dataset reiterates that stage and debulking remains the most important predictors of prognosis in this setting., (Copyright © 2015 Elsevier Inc. All rights reserved.)