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Objectives: To determine the impact of adjuvant therapy on oncologic outcomes in patients with 2009 International Federation of Gynecology and Obstetrics (FIGO) stage IA, IB, or II endometrial clear cell carcinoma (ECCC)., Methods: We conducted a retrospective review at 4 international institutions. Patients with newly diagnosed clinical stage I or II disease of either clear cell or mixed histology with a clear cell component treated between 01/01/2000-12/31/2015 were included. Oncologic outcomes were assessed for patients based on adjuvant treatment received, including chemotherapy, radiation, or chemotherapy with radiation., Results: Of 125 patients identified and analyzed, 77 (61.6%) had clear cell histology and 118 (94.4%) had stage I disease. Median age at diagnosis was 65 years (range, 33-91). All patients underwent hysterectomy, bilateral salpingo-oophorectomy, and lymph node assessment. Twenty-five patients (20.0%) underwent surgical management alone and 100 (80.0%) received adjuvant therapy: 20 (16.0%) received postoperative chemotherapy, 47 (37.6%) received postoperative radiation, and 33 (26.4%) received postoperative chemotherapy with radiation. Median follow-up was 88.4 months (range, <1-234). Progression-free survival (PFS) or overall survival (OS) did not significantly differ between surgery alone and type of adjuvant therapy (P = 0.18 and P = 0.56, respectively). Patients with mixed ECCC did not have a survival advantage over those with pure ECCC (5-year PFS rate, 85.0% vs 82.7%, P = 0.77; 5-year OS rate, 88.3% vs 91.2%, P = 0.94)., Conclusions: Receipt of adjuvant therapy in surgically staged I/II ECCC did not appear to offer a survival advantage over observation alone. Adjuvant therapy in early-stage ECCC with consideration of molecular classification should be evaluated., Competing Interests: Declaration of competing interest Dr. Leitao reports personal fees from Medtronic, Intuitive Surgical, J&J/Ethicon, and Immunogen. Dr. Abu-Rustum reports research funding paid to the institution from GRAIL. Dr. Eriksson reports speaker fees from Intuitive Surgical and AstraZeneca. Dr. Makker reports unpaid consulting/advisory roles with the following: Duality, Novartis, Morphosys, AstraZeneca, Eisai, Clovis Oncology, Karyopharm Therapeutics, GlaxoSmithKline, Merck, ArQule, Cullinan, Faeth Therapeutics, Jazz, Immunocore, Iteos Therapeutics, Ideaya, Kartos Therapeutics, Lilly, Moreo, Prelude, Takeda, and Zymeworks; research funding from the following: Merck (Inst), Eisai (Inst), AstraZeneca (Inst), Clovis Oncology (Inst), Bayer (Inst), Takeda (Inst), Duality (Inst), Zymeworks (Inst), Karyopharm Therapeutics (Inst), Faeth Therapeutics (Inst), Bristol-Myers Squibb (Inst), Lilly (Inst), and Cullinan (Inst); travel, accommodations, and expenses from the following: Eisai, Merck, AstraZeneca; and a relationship with IBM. Dr. du Bois reports honoraria/expenses from Amgen, AstraZeneca, BIOCAD, Clovis, GSK/Tesaro, Roche, and Zodiac; and consulting/advisory board role for Amgen, AstraZeneca, BIOCAD, Clovis, Genmab/Seattle Genetics, GSK/Tesaro, MSD, Roche, Pfizer. The other authors do not have potential conflicts of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To determine the safety and efficacy of the oral progesterone antagonist onapristone extended release (onapristone-XR) in patients with recurrent progesterone receptor (PR)-positive adult-type granulosa cell tumor (aGCT), low-grade serous ovarian cancer (LGSOC), or endometrioid endometrial cancer (EEC)., Methods: This single-institution phase II study included patients with PR-positive aGCT, LGSOC, or EEC who received ≥1 prior line of chemotherapy. Patients were enrolled from 5/2019-5/2020. PR status was evaluated via immunohistochemistry. Eligible patients had PR expression ≥1% on tissue collected within 3 years of enrollment. Patients received 50 mg of onapristone-XR twice daily until disease progression or treatment discontinuation. Adverse events were graded by Common Terminology Criteria for Adverse Events version 5.0. The primary endpoint was overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors 1.1. Secondary endpoints were response duration, clinical benefit rate (CBR), and safety., Results: Five patients with LGSOC and 1 with EEC enrolled, but both cohorts closed early due to slow accrual. Fourteen patients with aGCT enrolled and completed stage 1 accrual. No responses were observed. Four patients with LGSOC were evaluable, with median PFS of 4.4 months (range, 1.8-NE) and CBR of 50% (range, 6.8%-93.2%). All 14 patients with aGCT were evaluable, with median PFS of 2.8 months (range, 1.6-4.9), 6-month PFS rate of 21.4% (range, 5.2%-44.8%), 12-month PFS rate of 14.3% (range, 2.3%-36.6%), and a CBR of 35.7% (range, 12.8%-64.9%)., Conclusions: The study did not meet its primary endpoint. While onapristone-XR was well tolerated in all 3 arms, no objective responses were observed., Competing Interests: Declaration of competing interest Alexia Iasonos reports consulting fees from Mylan. Chrisann Kyi reports grant funding from Conquer Cancer Foundation; grant funding paid to the institution from Merus, Gritstone, and BMS; and consulting fees from Scenic Immunology B.V. and OncLive. Rachel N. Grisham reports honoraria from GSK, AstraZeneca, Natera, Springworks, Corcept, MJH, and PER. Carol Aghajanian reports clinical trial funding paid to the institution from AstraZeneca; consulting fees (advisory board) from Eisai/Merck, Roche/Genentech, Abbvie, AstraZeneca/Merck, and Repare Therapeutics; advisory board participation (no fee) for Blueprint Medicine; and leadership/fiduciary roles for the GOG Foundation Board of Directors (travel cost reimbursement) and NRG Oncology Board of Directors (unpaid). Claire F. Friedman reports ongoing institutional research support from Merck, BMS, AstraZeneca, Mersana, Hotspot Therapeutics, Immunocore, Marengo and Volastra; consulting fees from BMS, Seagen, Aadi Biosciences, and Eli Lilly; honoraria for lectures from Onclive; meeting/travel support by Puma Biotechnology; and participation on Data Safety Monitoring or Advisory Board of Merck, Genentech, and Marengo (all uncompensated). Roisin E. O'Cearbhaill reports personal fees from Tesaro/GSK, Regeneron, R-PHARM, Seattle Genetics, Fresenius Kabi, Gynecologic Oncology Foundation, Bayer, Curio, Miltenyi, 2seventybio and Immunogen, and other from Hitech Health, all outside the submitted work. She is a non-compensated steering committee member for the PRIMA, Moonstone (Tesaro/GSK), and DUO-O (AstraZeneca) studies and non-compensated advisor for Carina Biotech. Her institute receives funding for clinical research from Bayer/Celgene/Juno, Gynecologic Oncology Foundation, Genentech, Kite Pharma, Tesaro/GSK, Ludwig Cancer Institute, TCR2 Therapeutics, Genmab/Seagen Therapeutics, MarkerTherapeutics, Syndax Pharmaceuticals, Merck, Sellas Therapeutics, Abbvie/StemCentrx, Regeneron, Lyell Immunopharma, Acrivon, and Atara Biotherapeutics. Britta Weigelt reports a research grant from REPARE Therapeutics paid to the institution and has an immediate family member who is employed by AstraZeneca, outside the submitted work. Vicky Makker reports unpaid consulting/advisory roles with the following: Duality, Novartis, Morphosys, AstraZeneca, Eisai, Clovis Oncology, Karyopharm Therapeutics, GlaxoSmithKline, Merck, ArQule, Cullinan, Faeth Therapeutics, Jazz, Immunocore, Iteos Therapeutics, Ideaya, Kartos Therapeutics, Lilly, Moreo, Prelude, Takeda, and Zymeworks; research funding from the following: Merck (Inst), Eisai (Inst), AstraZeneca (Inst), Clovis Oncology (Inst), Bayer (Inst), Takeda (Inst), Duality (Inst), Zymeworks (Inst), Karyopharm Therapeutics (Inst), Faeth Therapeutics (Inst), Bristol-Myers Squibb (Inst), Lilly (Inst), and Cullinan (Inst); travel, accommodations, and expenses from the following: Eisai, Merck, AstraZeneca; and a relationship with IBM. Dennis S. Chi reports personal fees from Apyx Medical, Verthermia Inc., Biom ‘Up, and AstraZeneca, as well as recent or current stock/options ownership of Apyx Medical, Verthemia, Intuitive Surgical, Inc., TransEnterix, Inc., Doximity, Moderna, and BioNTech SE. The other authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To report long-term efficacy and safety of selinexor maintenance therapy in adults with TP53 wild-type (TP53wt) stage IV or recurrent endometrial cancer (EC) who achieved partial remission (PR) or complete remission (CR) following chemotherapy., Methods: Analysis of the prespecified, exploratory subgroup of patients with TP53wt EC from the phase 3 SIENDO study was performed. Progression-free survival (PFS) benefit in patients with TP53wt EC and across other patient subgroups were exploratory endpoints. Safety and tolerability were also assessed., Results: Of the 263 patients enrolled in the SIENDO trial, 113 patients had TP53wt EC; 70/113 (61.9%) had TP53wt/proficient mismatch repair (pMMR) EC, and 29/113 (25.7%) had TP53wt/deficient mismatch repair (dMMR) EC. As of April 1, 2024, the median PFS (mPFS) for TP53wt patients who received selinexor compared with placebo was 28.4 versus 5.2 months (36.8-month follow-up, HR 0.44; 95% CI 0.27-0.73). A benefit in mPFS was seen with selinexor versus placebo regardless of MMR status (patients with TP53wt/pMMR EC: 39.5 vs 4.9 months, HR 0.36; 95% CI 0.19-0.71; patients with TP53wt/dMMR EC: 13.1 vs 3.7 months, HR 0.49; 95% CI 0.18-1.34). Selinexor treatment was generally manageable, with no new safety signals identified., Conclusion: In the phase 3 SIENDO study, selinexor maintenance therapy showed a promising efficacy signal and a manageable safety profile in the prespecified subgroup of patients with TP53wt EC who achieved a PR or CR following chemotherapy. These results are being further evaluated in an ongoing randomized phase 3 trial (NCT05611931)., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: HER2 overexpression is associated with decreased overall survival in metastatic endometrial cancer. Trastuzumab with chemotherapy has demonstrated efficacy for first-line management of advanced HER2+ endometrial carcinoma, but HER2-directed therapy in the recurrent setting is limited. Zanidatamab (ZW25), a humanized, bispecific antibody that simultaneously binds the 2 distinct HER2 epitopes bound by trastuzumab and pertuzumab, has demonstrated safety and activity in HER2+ tumors. Here, we report the results of a phase 2, open-label study evaluating the efficacy and safety of zanidatamab in patients with HER2+ metastatic endometrial carcinoma/carcinosarcoma who received prior treatment., Methods: We enrolled 16 patients with HER2+ endometrial carcinoma/carcinosarcoma after progression on ≤2 lines of therapy on a single-arm phase 2 study of zanidatamab. The primary endpoint was overall response rate (ORR; complete or partial response) by Response Evaluation Criteria in Solid Tumors version 1.1. HER2 immunohistochemistry and fluorescence in situ hybridization (FISH) were performed on pretreatment samples. Intratumor HER2 genetic heterogeneity was assessed., Results: This study did not meet its primary efficacy endpoint. Although a clinical benefit rate of 37.5% was observed by 24 weeks, only 1 patient achieved a partial response (ORR, 6.2%). Eight patients had HER2 intratumor heterogeneity or lacked HER2 amplification by FISH. Decreased HER2 expression on repeat pretreatment samples was observed in 3 (75%) of 4 patients evaluated., Conclusions: We observed a low response rate to zanidatamab in recurrent HER2+ endometrial carcinoma/carcinosarcoma, which may be driven by downregulation of HER2 expression. Repeat HER2 testing should be considered prior to second-line HER2-directed therapy., Clinicaltrials: govidentifier: NCT04513665., Competing Interests: Declaration of Competing Interest V Makker reports meeting/travel support by Eisai and Merck; participation on Data Safety Monitoring or Advisory Board of Duality, Merck, Karyopharm, Exelexis, Eisai, Karyopharm, BMS, Clovis, Faeth Immunocore, Morphosys, AstraZeneca, Novartis, GSK, Bayer (all unpaid); and study support to the institution by Merck, Eisai, AstraZeneca, Faeth, Karyopharm, Zymeworks, Duality, Clovis, Bayer and Takeda. CF Friedman reports institutional research support from Seagen, Merck, BMS, AstraZeneca, Mersana, and Hotspot Therapeutics; consulting fees from BMS, Seagen, and Aadi Biosciences; honoraria for lectures from Onclive; meeting/travel support by PUMA; and participation on Data Safety Monitoring or Advisory Board of Merck, Genentech, and Marengo (all uncompensated). A Iasonos reports consulting fees from Mylan. MM Rubinstein reports research funding from Merk, Zentalis, and AstraZeneca. C Kyi reports grant funding from Conquer Cancer Foundation; grant funding paid to the institution from Merus, Gritstone, and BMS; and consulting fees from Scenic Immunology B.V. and OncLive. RN Grisham reports honoraria from GSK, AstraZeneca, Natera, Springworks, Corcept, MJH, and PER. C Aghajanian reports clinical trial funding paid to the institution from AstraZeneca; consulting fees (advisory board) from Eisai/Merck, Roche/Genentech, Abbvie, AstraZeneca/Merck, and Repare Therapeutics; advisory board participation (no fee) for Blueprint Medicine; and leadership/fiduciary roles for the GOG Foundation Board of Directors (travel cost reimbursement) and NRG Oncology Board of Directors (unpaid). The other authors do not have potential conflicts of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To compare clinical and pathologic characteristics of women with surgical stage I endometrial carcinoma by location of first recurrence and describe characteristics of isolated vaginal recurrence., Methods: Patients with 2009 International Federation of Obstetrics and Gynecology (FIGO) stage I endometrial carcinoma treated at two large cancer centers from 1/1/2009-12/31/2017 were identified. Sarcoma histology was excluded. Recurrences were grouped into isolated vaginal or extravaginal. Isolated vaginal recurrences were localized by anatomic location within the vaginal vault. Clinical and pathologic variables were compared with chi-square analysis, and Kaplan-Meier curves with log-rank tests., Results: Of 2815 women identified, 278 (10%) experienced a recurrence. Sixty-one patients (2%) had an isolated vaginal recurrence, including 42 (69%) at the vaginal apex; 217 (8%) had an extravaginal recurrence, including 18 with a vaginal component. Median time to recurrence was 11 months (range, 1-68) for isolated vaginal recurrence and 20 months (range, 1-98) for extravaginal recurrence (P < .004). Of 960 patients (34%) treated with adjuvant vaginal brachytherapy (VBT), 156 (16%) recurred; 19 (2%) had an isolated vaginal recurrence, including 16 (84%) at the vaginal apex. Three-year PFS rates for isolated vaginal recurrence were 97.6% (SE ± 0.4%) with minimally invasive surgery (MIS) versus 96.9% (SE ± 1.1%) with open (P = .8), and for extravaginal recurrence were 91.8% (SE ± 0.7%) with MIS versus 90.8% (SE ± 1.8%) with open (P = .8)., Conclusions: Isolated vaginal recurrences in stage I endometrial cancer are detected earlier than non-vaginal recurrences. Surgical approach does not appear to impact recurrence. Adjuvant VBT after primary surgery carries a 1%-2% risk of isolated vaginal apex recurrence., Competing Interests: Declaration of Competing Interest Outside the submitted work, N.R. Abu-Rustum reports Stryker/Novadaq and GRAIL grants paid to the institution. V. Makker reports meeting/travel support by Eisai and Merck; participation on a Data Safety Monitoring or Advisory Board of Duality, Merck, Karyopharm, Exelexis, Eisai, Karyopharm, BMS, Clovis, Faeth Immunocore, Morphosys, AstraZeneca, Novartis, GSK, Bayer (all unpaid), and study support to the institution by Merck, Eisai, AstraZeneca, Faeth, Karyopharm, Zymeworks, Duality, Clovis, Bayer, and Takeda. M.M. Leitao Jr. reports research funding paid to the institution from KCI/Acelity, ad-hoc speaker for Intuitive Surgical, Inc., and advisory board participation for JnJ/Ethicon and Takeda. Y. Lakhman serves as a consultant for Calyx Clinical Trial Solutions. A. Jhingran reports a consulting agreement and advisory board participation with Genentech, and a patent (adaptive intracavitary brachytherapy applicator for cervical cancer). The other authors do not have potential conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: This phase 2 study investigated sapanisertib (selective dual inhibitor of mTORC1/2) alone, or in combination with paclitaxel or TAK-117 (a selective small molecule inhibitor of PI3K), versus paclitaxel alone in advanced, recurrent, or persistent endometrial cancer., Methods: Patients with histologic diagnosis of endometrial cancer (1-2 prior regimens) were randomized to 28-day cycles on four treatment arms: 1) weekly paclitaxel 80 mg/m 2 (days 1, 8, and 15); 2) weekly paclitaxel 80 mg/m 2  + oral sapanisertib 4 mg on days 2-4, 9-11, 16-18, and 23-25; 3) weekly sapanisertib 30 mg, or 4) sapanisertib 4 mg + TAK-117 200 mg on days 1-3, 8-10, 15-17, and 22-24., Results: Of 241 patients randomized, 234 received treatment (paclitaxel, n = 87 [3 ongoing]; paclitaxel+sapanisertib, n = 86 [3 ongoing]; sapanisertib, n = 41; sapanisertib+TAK-117, n = 20). The sapanisertib and sapanisertib+TAK-117 arms were closed to enrollment after futility analyses. After a median follow-up of 14.4 (paclitaxel) versus 17.2 (paclitaxel+sapanisertib) months, median progression-free survival (PFS; primary endpoint) was 3.7 versus 5.6 months (hazard ratio [HR] 0.82; 95% confidence interval [CI] 0.58-1.15; p = 0.139); in patients with endometrioid histology (n = 116), median PFS was 3.3 versus 5.7 months (HR 0.66; 95% CI 0.43-1.03). Grade ≥ 3 treatment-emergent adverse event rates were 54.0% with paclitaxel versus 89.5% paclitaxel+sapanisertib., Conclusions: Our findings support inclusion of chemotherapy combinations with investigational agents for advanced or metastatic disease. The primary endpoint was not met and toxicity was manageable., Trial Registration: ClinicalTrials.gov number, NCT02725268., Competing Interests: Declaration of Competing Interest Ana Oaknin reports receiving institutional funding from Abbvie Deutschland, Advaxis Inc., Aeterna Zentaris, Amgen, Aprea Therapeutics AB, Bristol Myers Squibb, Clovis Oncology, Eisai Co., Ltd., F. Hoffmann–La Roche Ltd., Immunogen Inc., Merck Sharp & Dohme de España SA, Millennium Pharmaceuticals Inc., PharmaMar SA, Regeneron Pharmaceuticals and Tesaro Inc.; personal fees for travel and/or accommodation from AstraZeneca, PharmaMar and Roche; personal fees for advisory board membership from Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Eisai Co., Ltd., EMD Serono, F. Hoffmann–La Roche Ltd., Genmab, GSK, ImmunoGen, Itheos, Merck Sharp & Dohme de España, SA, Mersana Therapeutics, Novocure, PharmaMar, Sattucklabs, Seagen, and Sutro Biopharma; membership for ASCO, GOG, and SEOM; a non-remunerated role (member and Cervix Cancer Chair on behalf of GEICO) for GCIG; and being an unpaid member, Officer, Co-Chair of the ESMO Gynaecological Cancers Congress 2023–2025, Chair of the Gynaecological Track ESMO 2019, Scientific Track Member Gynaecological Cancers ESMO 2018, ESMO 2020, and ESMO 2022, member of the Gynaecological Cancers Faculty, and Subject Editor for the Gynaecological Clinical Practice Guidelines. Francesco Raspagliesi has received payment or honoraria from GSK, MSD, and AstraZeneca as well as support for attending meetings and/or travel from GSK. Robert M. Wenham reports receiving personal and institutional fees from Merck and Ovation Diagnostics; institutional clinical trial fees from AstraZeneca, Abbvie, Regeneron, and Eisai Co., Ltd.; personal consulting fees from Merck, Legend Biotech, Novacure, Genentech, GSK/Tesaro, AstraZeneca, Abbvie, Ovation Diagnostics, Regeneron, Seagen, Shattuck Labs, Eisai Co., Ltd., and Immunogen; speakers fees from Clovis Oncology; support for attending meetings and/or travel as part of the consulting, board participation, or abstract preparation, not in isolation; travel fees from Sonnet Biotherapeutics and Eisai Co., Ltd.; personal/DSMB fees from Seagen and GSK/Tesaro; personal/scientific advisory board fees from Sonnet Biotherapeutics; and personal stock or stock options for Ovation Diagnostics. Elena Ioana Braicu reports receiving research funding from Bayer and Tesaro; personal fees from Clovis Oncology, Tesaro, Eisai Co., Ltd., and RochePharma; and both research funding and personal fees from Roche Diagnostics, GSK, and AstraZeneca. Vicky Makker reports research funding (institution) from AstraZeneca, Bayer, Bristol Myers Squibb, Clovis Oncology, Duality, Eisai Co., Ltd., Faeth Therapeutics, Karyopharm Therapeutics, Lilly, MSD, Takeda, and Zymeworks; an unpaid consulting or advisory role for ArQule, AstraZeneca, Clovis Oncology, Duality, Eisai Co., Ltd., Faeth Therapeutics, GlaxoSmithKline, IBM, Immunocore, ITeos Therapeutics, Kartos Therapeutics, Karyopharm Therapeutics, Lilly, MSD, Moreo, Morphosys, Novartis, Takeda, and Zymeworks; support for travel, accommodations, and/or expenses from Eisai Co., Ltd. and MSD. Eva María Guerra Alía reports advisory/consultancy honorarium from AstraZeneca-MSD, Clovis Oncology, GSK-Tesaro, PharmaMar, and Roche; speaker bureau/expert testimony honorarium from AstraZeneca-MSD, PharmaMar, Roche, and GSK-Tesaro; and support for travel, accommodation, and/or expenses from Roche, GSK-Tesaro, and Baxter. Zhenqiang Su is an employee of Takeda. Sylvie Vincent is an employee of Takeda. Farhad Sedarati is an employee of Takeda. Douglas V. Faller reports consulting fees from Viracta Therapeutics, Briacell Therapeutics, and Molecular Partners; equity from Oryzon Genomics, Phoenicia Biosciences, Viracta Therapeutics, and Briacell Therapeutics; and employment at Oryzon Genomics, Phoenicia Biosciences, and Takeda Pharmaceuticals (ended in 2022). Sileny N. Han, Amit Oza, Nicoletta Colombo, Andrea Jewell, Jonathan Krell, Jean- François Baurain, Rachel Neuwirth, and Giovanni Scambia have no disclosures to report., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate adverse events (AEs) of combination lenvatinib plus pembrolizumab for the treatment of recurrent endometrial cancer (EC) and to assess outcomes by lenvatinib starting dose., Methods: We retrospectively reviewed patients with recurrent EC treated with lenvatinib plus pembrolizumab at our institution between 10/1/2019-11/30/2021. Starting dose of lenvatinib was defined as standard (20 mg) or reduced (10 mg/14 mg). AEs were manually extracted through chart review and graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. PFS, overall survival (OS), and duration of response (DOR) were analyzed., Results: Forty-three patients were identified; median age was 67 years (range, 54-85). The most common histologies were serous (35%), endometrioid (23%), and carcinosarcoma (21%). Starting lenvatinib doses were 10 mg (n = 10), 14 mg (n = 10), and 20 mg (n = 23). Median number of cycles received was 8 (range, 1-42). Twenty-four patients (56%) required ≥1 lenvatinib dose reduction; 3 (7%) discontinued lenvatinib, and 1 (2%) discontinued pembrolizumab for intolerance or AE. Thirty-six patients (84%) experienced grade ≥ 3 AEs; hypertension, weight loss, anemia, fatigue, and thrombocytopenia were most common. The standard dose group experienced significantly shorter observed PFS vs the reduced dose group (P = .02). There was no difference in DOR (P = .09) or OS (P = .27) between the groups., Conclusion: In clinical practice, AEs associated with combination lenvatinib plus pembrolizumab were common and comparable to Study 309/KEYNOTE-775 findings. AEs were similar regardless of starting lenvatinib dose. Further dose optimization studies of lenvatinib plus pembrolizumab may be indicated in recurrent EC. Clinical trial data remain the gold standard to guide starting lenvatinib dosing., Competing Interests: Declaration of Competing Interest Outside the current study, A. Iasonos reports consulting fees from Mylan. N.R. Abu-Rustum reports honoraria from Klinik Essen Germany and NCCN; and GRAIL grants paid to the institution. V. Makker reports meeting/travel support by Eisai and Merck; participation on Data Safety Monitoring or Advisory Board of Duality, Merck, Karyopharm, Exelexis, Eisai, Karyopharm, BMS, Clovis, Faeth Immunocore, Morphosys, AstraZeneca, Novartis, GSK, Bayer (all unpaid), and study support to the institution by Merck, Eisai, AztraZeneca, Faeth, Karyopharm, Zymeworks, Duality, Clovis, Bayer and Takeda. C. Aghajanian reports clinical trial funding paid to the institution from AstraZeneca; consulting fees (advisory board) from Eisai/Merck, Roche/Genentech, Abbvie, AstraZeneca/Merck, and Repare Therapeutics; advisory board participation (no fee) for Blueprint Medicine; and leadership/fiduciary roles for the GOG Foundation Board of Directors (travel cost reimbursement) and NRG Oncology Board of Directors (unpaid). M. Rubinstein reports research funding from Merk, Zentalis, and AstraZeneca. A.K. Green reports research funding from Eli Lilly, Mereo Biopharma, and the American Society for Clinical Oncology (ASCO), and personal fees from Merck. All other authors have no potential conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: We sought to compare outcomes between minimally invasive surgery (MIS) and laparotomy in patients with clinical stage I uterine serous carcinoma (USC)., Methods: Patients who underwent surgery for newly diagnosed USC between 11/1/1993 and 12/31/2017 were retrospectively identified and assigned to either the MIS cohort or the laparotomy cohort. Patients with conversion to laparotomy were analyzed with the MIS cohort. Chi-square and Mann-Whitney tests were used to compare categorical and continuous variables, respectively. Kaplan-Meier curves were used to estimate survival and compared using the log-rank test., Results: In total, 391 patients met inclusion criteria; 242 underwent MIS (35% non-robotic and 65% robotic-assisted laparoscopies) and 149 underwent laparotomy. Age, BMI, stage, and washings status did not differ between cohorts. Patients who underwent MIS were less likely to have lymphovascular space invasion (LVSI; 35.1% vs 48.3%), had fewer nodes removed (median, 9 vs 15), and lower rates of paraaortic nodal dissection (44.6% vs 65.1%). Rates of adjuvant therapy did not differ between cohorts. Median follow-up times were 63.0 months (MIS cohort) vs 71.0 months (laparotomy cohort; P = .04). Five-year PFS rates were 58.7% (MIS) vs 59.8% (laparotomy; P = .1). Five-year OS rates were 65.2% (MIS) compared to 63.5% (laparotomy; P = .2). On multivariable analysis, higher stage, deep myometrial invasion, and positive washings were associated with decreased PFS. Age ≥ 65 years, higher stage, LVSI, and positive washings were associated with shorter OS., Conclusions: MIS does not compromise outcomes in patients with newly diagnosed USC and should be offered to these patients to minimize surgical morbidity., Competing Interests: Declaration of Competing Interest N.R. Abu-Rustum reports research funding paid to the institution from GRAIL. M.M. Leitao Jr. reports research funding paid to the institution from KCI/Acelity, ad-hoc speaker for Intuitive Surgical, Inc., and advisory board participation for JnJ/Ethicon and Takeda. V. Makker reports advisory board participation (unpaid) for Eisai, Merck, Clovis, Faeth, Duality, Morphyes, Karyopharm, Novartis, Lilly, and Immunocore. All other authors have no potential conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Oral tyrosine kinase inhibitors (TKIs) have new indications for treatment in gynecologic malignancies. These targeted drugs have both unique and overlapping toxicities, which require careful attention and management. New combination therapies with immune-oncology agents have demonstrated promise in endometrial cancer. This review examines common adverse events associated with TKIs and provides readers with an evidence-based review on current uses and strategies for the management of these medications., Methods: A comprehensive review of the medical literature on TKI use in gynecologic cancer was undertaken by a committee approach. Details of each drug, its molecular target, and relevant data on both clinical efficacy and side effects were compiled and organized for clinical use. Information on drug-related secondary effects and management strategies for specific toxicities, including dose reduction and concomitant medications, were gathered., Results: TKIs can potentially offer improved response rates and durable responses for a group of patients who were previously without an effective standard second-line therapy. The combination of lenvatinib and pembrolizumab represents a more targeted approach to the drivers of endometrial cancer; however, there remains significant drug-related toxicity, and thus dose reduction and dose delay are frequently required. Toxicity management requires frequent check-ins and management strategies to help patients find the highest tolerable dose. TKIs are expensive and patient financial toxicity is as critical a measure of a drug's utility as any drug side effect. Many of these drugs have patient assistance programs, which should be fully utilized to minimize cost., Conclusions: Future studies are needed to expand the role of TKIs into new molecularly driven groups. Attention to cost, durability of response, and long-term toxicity management is needed to ensure all eligible patients have access to treatment., Competing Interests: Declaration of Competing Interest, (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Using next generation sequencing (NGS), The Cancer Genome Atlas (TCGA) found that endometrial carcinomas (ECs) fall under one of four molecular subtypes, and a POLE mutation status, mismatch repair (MMR) and p53 immunohistochemistry (IHC)-based surrogate has been developed. We sought to retrospectively classify and characterize a large series of unselected ECs that were prospectively subjected to clinical sequencing by utilizing clinical molecular and IHC data., Experimental Design: All patients with EC with clinical tumor-normal MSK-IMPACT NGS from 2014 to 2020 (n = 2115) were classified by integrating molecular data (i.e., POLE mutation, TP53 mutation, MSIsensor score) and MMR and p53 IHC results. Survival analysis was performed for primary EC patients with upfront surgery at our institution., Results: Utilizing our integrated approach, significantly more ECs were molecularly classified (1834/2115, 87%) as compared to the surrogate (1387/2115, 66%, p < 0.001), with an almost perfect agreement for classifiable cases (Kappa 0.962, 95% CI 0.949-0.975). Discrepancies were primarily due to TP53 mutations in p53-IHC-normal ECs. Of the 1834 ECs, most were of copy number (CN)-high molecular subtype (40%), followed by CN-low (32%), MSI-high (23%) and POLE (5%). Histologic and genomic variability was present amongst all molecular subtypes. Molecular classification was prognostic in early- and advanced-stage disease, including early-stage endometrioid EC., Conclusions: The integration of clinical NGS and IHC data allows for an algorithmic approach to molecularly classifying newly diagnosed EC, while overcoming issues of IHC-based genetic alteration detection. Such integrated approach will be important moving forward given the prognostic and potentially predictive information afforded by this classification., Competing Interests: Conflicts of interest N.R. Abu-Rustum reports Stryker/Novadaq and GRAIL grants paid to the institution, outside the current study. C.F. Friedman reports institutional research support from Seagen, Merck, BMS, AstraZeneca, Mersana and Hotspot Therapeutics; consulting fees from BMS, Seagen and Aadi Biosciences; honoraria for lectures from Onclive; meeting/ travel support by Puma; participation on Data Safety Monitoring or Advisory Board of Merck, Genentech and Marengo (all uncompensated). D. Zamarin reports institutional research support from AstraZeneca, Merck, Plexxikon Synthekine and Genentech; consulting fees from AstraZeneca, Synthekine, Astellas, Tessa Therapeutics, Memgen, Celldex, Crown Biosciences, Hookipa Biotech, Kalivir, Xencor and GSK; royalties from Merck; and stock options from Accurius Therapeutics, ImmunOS Therapeutics and Calidi Biotherapeutics, all outside the submitted work. V. Makker reports meeting/travel support by Eisai and Merck; participation on Data Safety Monitoring or Advisory Board of Duality, Merck, Karyopharm, Exelexis, Eisai, Karyopharm, BMS, Clovis, Faeth Immunocore, Morphosys, AstraZeneca, Novartis, GSK, Bayer (all unpaid), and study support to the institution by Merck, Eisai, AztraZeneca, Faeth, Karyopharm, Zymeworks, Duality, Clovis, Bayer and Takeda. Y. Liu reports institutional research funding from Repare Therapeutics, AstraZeneca and GSK; honoraria from Total Health and Sarah Lawrence College; and travel/meeting support by AstraZeneca, outside the submitted work. B. Weigelt reports a research grant from REPARE Therapeutics paid to the institution, outside the submitted work. D.S. Chi reports personal fees from Apyx Medical, Verthermia Inc., Biom ‘Up, and AstraZeneca, as well as recent or current stock/options ownership of Apyx Medical, Verthemia, Intuitive Surgical, Inc., TransEnterix, Inc., Doximity, Moderna, and BioNTech SE. E.L. Jewell reports personal fees from Covidien/Medtronic. M. M. Leitao is an ad hoc speaker for Intuitive Surgical, Inc.; outside the submitted work, he is on the Advisory Board of Ethicon/Johnson & Johnson and Takeda; and reports grants paid to the institution by KCI/Acelity. C. Aghajanian reports clinical trial funding paid to the institution from AstraZeneca; consulting fees (advisory board) from Eisai/Merck, Roche/Genentech, Abbvie, AstraZeneca/Merck, and Repare Therapeutics; advisory board participation (no fee) for Blueprint Medicine; and leadership/fiduciary roles for the GOG Foundation Board of Directors (travel cost reimbursement) and NRG Oncology Board of Directors (unpaid). The remaining authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: To describe the prevalence of germline pathogenic variants (gPVs) in endometrial and ovarian carcinosarcomas and determine if gPVs are drivers of carcinosarcoma., Methods: Patients with endometrial or ovarian carcinosarcomas who underwent clinical tumor-normal sequencing from 1/1/2015 to 6/1/2021 and consented to germline assessment of ≥76 cancer predisposition genes were included. In patients with gPVs, biallelic inactivation was identified through analysis of loss of heterozygosity and somatic pathogenic alterations., Results: Of 216 patients identified, 167 (77%) were diagnosed with endometrial carcinosarcoma and 49 (23%) with ovarian carcinosarcoma. Overall, 33 gPVs were observed in 29 patients (13%); 20 gPVs (61%) had biallelic loss in tumors. The rate of high-penetrance gPVs overall was 7% (16 of 216); 88% of high-penetrance gPVs had biallelic loss. In the endometrial carcinosarcoma cohort, 22 gPVs were found in 19 (11%) of 167 patients; 12 gPVs (55%) had biallelic loss in tumors, including 8 (89%) of 9 in high-penetrance gPVs. Among the ovarian carcinosarcoma cohort, 11 gPVs were found in 10 (20%) of 49 patients; 8 gPVs (73%) had biallelic loss in tumors, and all evaluable high-penetrance gPVs (n = 6) had biallelic loss. All gPVs in homologous recombination (BRCA1, BRCA2, RAD51C) and Lynch syndrome (MSH2, MSH6) genes had biallelic loss in tumors (n = 15)., Conclusions: gPVs in genes affecting homologous recombination- or Lynch-associated mismatch repair exhibited biallelic inactivation within tumors, suggesting likely drivers of gynecologic carcinosarcoma. Our data support germline testing for patients with gynecologic carcinosarcomas, given implications for treatment and risk-reduction in patients and at-risk family members., Competing Interests: Declaration of Competing Interest B.Weigelt reports research funding and scientific advisory board participation from Repare Therapeutics, outside the submitted work. K. Offit is a founder and shareholder of AnaNeo Therapeutics Incorporated. Z.K. Stadler has an immediate family member who serves as a consultant in Ophthalmology for Alcon, Adverum, Gyroscope Therapeutics Ltd., Neurogene and RegenexBio, outside the submitted work. M.F. Berger reports receiving research funding from GRAIL and advisory board activities for Eli Lilly, AstraZeneca, and PetDx. Y.L. Liu reports research funding from AstraZeneca, GSK, and Repare Therapeutics. N.R. Abu-Rustum reports research funding paid to the institution from GRAIL. C. Aghajanian reports clinical trial funding paid to the institution from AstraZeneca; consulting fees (advisory board) from Eisai/Merck, Roche/Genentech, Abbvie, AstraZeneca/Merck, and Repare Therapeutics; advisory board participation (no fee) for Blueprint Medicine; and leadership/fiduciary roles for the GOG Foundation Board of Directors (travel cost reimbursement) and NRG Oncology Board of Directors (unpaid). D.S. Chi reports personal fees from Apyx Medical, Verthermia Inc., Biom ‘Up, and AstraZeneca, as well as recent or current stock/options ownership of Apyx Medical, Verthemia, Intuitive Surgical, Inc., TransEnterix, Inc., Doximity, Moderna, and BioNTech SE. R.N. Grisham reports personal fees from AstraZeneca, Corcept, GlaxoSmithKline, MJH Life Sciences, Natera, PER, and SpringWorks. M.M. Leitao Jr. reports research funding paid to the institution from KCI/Acelity, ad-hoc speaker for Intuitive Surgical, Inc., and advisory board participation for JnJ/Ethicon and Takeda. V. Makker reports advisory board participation (unpaid) for Eisai, Merck, Clovis, Faeth, Duality, Morphyes, Karyopharm, Novartis, Lilly, and Immunocore. R.E. O'Cearbhaill reports honoraria from GSK, Bayer, Regeneron, SeaGen, Fresenius Kabi, Immunogen, MJH Life Sciences, Curio, R-Pharm, GOG Foundation, and Onclive/PER. M. Rubinstein reports research funding from Merk, Zentalis, and AstraZeneca. M.L. Hensley reports advisory board participation at Aadi Bioscience, GSK, Thrive Bioscience, and Lilly; has an immediate family member who is employed by Sanofi; and served as a CME faculty speaker for Research to Practice. All other authors have no potential conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Our understanding of the biologic heterogeneity of endometrial cancer has improved, but which patients benefit from single-agent versus combination immune checkpoint blockade remains unclear., Methods: We conducted a single-center, randomized, open-label, phase 2 study of durvalumab 1500 mg (Arm 1) versus durvalumab 1500 mg plus tremelimumab 75 mg every 4 weeks (Arm 2) in patients with endometrial carcinoma. The primary endpoints were overall response rate (ORR) and progression-free survival (PFS) at 24 weeks. Patients were stratified by mismatch repair (MMR) status and carcinosarcoma histology. Using a Simon two-stage minimax design, we determined 40 patients per arm would provide 90% power and Type 1 error of 10%., Results: Eighty-two patients were enrolled; 77 were evaluable for toxicity (Arm 1: 38, Arm 2: 39) and 75 evaluable for efficacy (Arm 1: 37, Arm 2: 38). Patient were stratified by MMR status (Arm 1: 5, Arm 2: 4 were MMR-deficient). The ORR in Arm 1 was 10.8% (one-sided 90% CI: 4.8-100%); the ORR in Arm 2 was 5.3% (one-sided 90% CI: 1.4-100%). Since the primary endpoint of ORR was not met, 24-week PFS was not compared to historical controls per protocol specification. No new safety signals were identified., Conclusions: In these patients with predominantly MMR-proficient endometrial cancer, there was limited response with single-agent and combined immune checkpoint blockade. The pre-specified efficacy thresholds were not met for further evaluation. A deeper understanding of potential mechanisms of resistance to immunotherapy in MMR-proficient endometrial cancer is needed for the development of novel therapeutic approaches., Competing Interests: Declaration of Competing Interest Dr. Rubinstein reports grant support paid to the institution from Merck, Zentalis, and AstraZeneca. Dr. Iasonos reports consulting fees from Mylan. Dr. Friedman reports grant support paid to the institution from Genentech/Roche, Bristol Myers Squibb (BMS), Merck, AstraZeneca, and Daiichi; consulting fees from Seagen and BMS; and waived compensation for advisory board participation from Merck and Genentech. Dr. O'Cearbhaill reports meeting/travel support from the Gynecologic Oncology Foundation, Curio, and Hitech Health; participation in the advisory boards of Tesaro/GlaxoSmithKline (GSK), Regeneron, Seattle Genetics, Fresenius Kabi, Bayer, and CarinaBiotech (non-compensated); non-compensated steering committee participation for Tesaro/GSK and AstraZeneca; and grant support paid to the institution from Bayer/Celgene/Juno, Tesaro/GSK, Merck, the Ludwig Cancer Institute, Abbvie/StemCentrx, Regeneron, TCR2 Therapeutics, Marker Therapeutics, Syndax Pharmaceuticals, Genmab/Seagen Therapeutics, Sellas Therapeutics, Genentech, KitePharma, and the Gynecologic Oncology Foundation. Dr. Cadoo reports grant support paid to the institution from The Irish Cancer Society, MSD, and Immunogen; consulting fees from Nextcure, MJH Life Sciences, and GSK; honoraria from SGK, AstraZeneca, and MSD; meeting/travel support from Roche, Pfizer, and MSD; and board/committee participation for MSD, AstraZeneca, GSK, Eisai, The National Cancer Control Programme Ireland (voluntary), and the ARC Cancer Support Centers (voluntary). Dr. Kyi reports grant support paid to the institution from Merus, Gritstone, and BMS; consulting fees from Scenic Immunology BV and OncLive; and meeting/travel support from the Conquer Cancer Foundation and Gritstone. Dr. Zamarin reports grant support paid to the institution from AstraZeneca, Roche, Plexxikon, and Synthekine; patents from Merck and Newcastle Disease Virus for Cancer Therapy; consulting fees from Memgen, Celldex, Agenus, Astellas, AstraZeneca, Crown Biosciences, Roche, GSK, Hookipa, ImmunOS, Kalivir, Synologic Therapeutics, Synthekine, Takeda, Targovax, Tessa Therapeutics, and Xencor; and stock options from Accurius Therapeutics, ImmunOS Therapeutics, and Calidi Biotherapeutics. Dr. Aghajanian reports grant support paid to the institution from Abbvie, Clovis, Genentech, and AstraZeneca; consulting fees from Eisai/Merck, Mersana Therapeutics, Roche/Genentech, Abbvie, AstraZeneca/Merck, and Repare Therapeutics; advisory board participation for Blueprint Medicine; and unpaid participation on the Board of Directors of the GOG Foundation and NRG Oncology. Dr. Billinson reports stock ownership in Abbvie and Johnson and Johnson. Dr. Makker reports unpaid board participation for Eisai, Merck, Clovis, Faeth, Duality, Morphyes, Karyopharm, Novartis, Lilly and Immunocore. The authors have no potential conflicts of interest to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Endometrial cancer incidence and mortality are rising among all ethnic groups. Carboplatin plus paclitaxel is the established frontline treatment for advanced/recurrent disease; however, subsequent treatment with traditional cytotoxic chemotherapy is challenging. The molecular characterization of endometrial cancer has provided important insights into the biological drivers of carcinogenesis, which has allowed for the development of newer precision immunotherapies and targeted therapies, including pembrolizumab, dostarlimab, and lenvatinib. Until recently, platinum rechallenge was often considered at the time of recurrence, given the lack of other available therapeutic options; however, "platinum sensitivity" in endometrial cancer is subjective and largely based on expert opinion and/or practitioner experience. Small retrospective studies have tried to provide guidance on the utility of platinum rechallenge, but they are limited by variable patient characteristics and small sample sizes. The applicability of these retrospective studies to contemporary clinical practice is difficult in the setting of changing patient demographics, a better understanding of endometrial cancer drivers, and the recent approvals of immune checkpoint inhibitors and the combination of lenvatinib plus pembrolizumab in the second-line setting. The primary focus of this review is to distill the available data regarding platinum-doublet chemotherapy rechallenge and highlight recent pivotal developments in endometrial cancer treatment, as well as future directions., Competing Interests: Conflict of interest statement Outside the submitted work, M Rubinstein reports funding from Merck, Zentalis, and AstraZeneca. V Makker reports advisory board participation for Eisai, Merck, Clovis, Faeth, Duality, Morphyes, Karyopharm, Novartis, Lilly, and Immunocore. A Nogueira-Rodrigues is a speaker for AstraZeneca, Merck, Roche, Daiichi Sankyo, Pfizer, Oncologia Brasil, and GSK; and is a consultant for Agenus, AstraZeneca, Eisai, Merck, Roche, and GSK. D Aoki reports consulting fees from Abbie, MSD, AstraZeneca, Takeda, Eisai, and Chugai; and personal fees from MSD, AstraZeneca, Eisai, Genmab, Takeda, Chugai, and Myriad Genetics. S Shen reports payment/honoraria from MJH Life Sciences. J Sehouli reports funding from GSK, Clovis, AstraZeneca, Tesaro, MSD, and Merck; consulting fees from GSK, Clovis, AstraZeneca, Tesaro, MSD, Merck, Roche, Pharmamar, and Eisai; payment/honoraria and advisory board from GSK, Clovis, AstraZeneca, Tesaro, MSD, Merck, Pharmamar, Novocure, and Incyte; payment from GSK, Clovis, AstraZeneca, Tesaro, MSD, Merck, Pharmamar, Novocure, and Eisai; support for meetings/travel from AstraZeneca, Roche, GSK, Tesaro, and Pharmamar; and leadership/fiduciary role for NOGGO, AGO, ENGAGE, and ESGO. DSP Tan reports consultancy fees and honoraria from AstraZeneca, Roche, MSD, Merck Serono, Bayer, Eisai, GSK, Boehringer Ingelheim; institutional research funding from AstraZeneca, Bayer, MSD, Eisai, BMS, Roche and Karyopharm; stock ownership of the Asian Microbiome Library (AMiLi); and support from the Singapore Ministry of Health's National Medical Research Council Clinician Scientist Award and Pangestu Family Foundation Gynaecological Cancer Research Fund. BJ Monk reports consulting fees from 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, and Zentalis; and payment/honoraria from AstraZeneca, Clovis, Easai, Merck, Myriad, Roche/Genentech, and TESARO/GSK., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To assess survival among patients diagnosed with uterine carcinosarcoma (CS) who underwent sentinel lymph node (SLN) biopsy alone vs. systematic lymph node dissection (LND)., Methods: We identified newly diagnosed CS patients who underwent primary surgical management from January 1996-December 2019. The SLN cohort underwent SLN biopsy alone with bilateral SLNs identified. The systematic LND cohort did not undergo SLN biopsy., Results: Ninety-nine patients underwent SLN biopsy, and 100 patients underwent systematic LND. There was no difference by age, stage, body mass index, myoinvasion (<50%, ≥50%), lymphovascular space invasion, or positive washings. Eighty-five SLN (85.9%) and 15 LND (15%) underwent minimally invasive surgery (P < 0.001). The median total node count was four (range, 1-13) for SLN and 19 (range, 2-50) for LND (P < 0.001). Nodal metastasis occurred in 23 (23.2%) SLN and in 22 (22%) LND (P = 0.4). Postoperative therapy was administered to 85 (85.9%) SLN and 71 (71%) LND (P = 0.02). Median follow-up was 33 months (range, 1-205) for SLN and 55.3 months (range, 1-269) for LND (P = 0.001). The three-year progression-free survival (PFS) was 62.9% (SE 5.2%) for SLN and 52.3% (SE 5.3%) for LND (P = 0.13). The three-year overall survival (OS) was 72.1% (SE 5.1%) for SLN and 71.6% (SE 4.6%) for LND (P = 0.68). An isolated nodal recurrence occurred in two (2%) SLN and four (4%) LND (P = 0.26)., Conclusions: There is no difference in PFS or OS among CS patients who undergo SLN biopsy vs. systematic LND. SLN biopsy detects nodal metastasis without compromising oncologic outcomes., Competing Interests: Declaration of Competing Interest Outside the submitted work, Dr. Makker reports industry support and unpaid consultant fees from Astra Zeneca, Eisai, Merck, Lilly, Karyopharm, Takeda, Genentech, Clovis, Novartis, Faeth, Zymeworks, GSK, and Moreo. Dr. Makker also discloses personal fees from IBM Watson. Dr. Abu-Rustum reports institutional grants from Stryker/Novadaq and GRAIL. Dr. Leitao reports grants from KCI/Acelity, personal fees from Takeda, J&J/Ethicon, and Intuitive Surgical. All other authors declare no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Clear cell endometrial carcinoma represents an uncommon and poorly understood entity. Data from molecular/genomic profiling highlighted the importance of various signatures in assessing the prognosis of endometrial cancer according to four classes of risk (POLE mutated, MMRd, NSMP, and p53 abnormal). Unfortunately, data specific to clear cell histological subtype endometrial cancer are lacking. More recently, data has emerged to suggest that most of the patients (more than 80%) with clear cell endometrial carcinoma are characterized by p53 abnormality or NSMP type. This classification has important therapeutic implications. Although it is an uncommon entity, clear cell endometrial cancer patients with POLE mutation seem characterized by a good prognosis. Chemotherapy is effective in patients with NSMP (especially in stage III and IV) and patients with p53 abnormal disease (all stages). While, preliminary data suggested that patients with MMRd are less likely to benefit from chemotherapy. The latter group appears to benefit much more from immune checkpoint inhibitors: recent data from clinical trials on pembrolizumab plus lenvatinib and nivolumab plus cabozantinib supported that immunotherapy plus tyrosine kinase inhibitors (TKI) would be the most appropriate treatment for recurrent non-endometrioid endometrial cancer (including clear cell carcinoma) after the failure of platinum-based chemotherapy. Moreover, ongoing clinical trials testing the anti-tumor activity of innovative products will clarify the better strategies for advanced/recurrent clear cell endometrial carcinoma. Further prospective evidence is urgently needed to better characterize clear cell endometrial carcinoma., Competing Interests: Declaration of Competing Interest Giorgio Bogani: Novartis AG Pharma (C/A, H), Italian Ministry of Health (RG). Nicole Concin: AstraZeneca (C/A, SH), Seattle Genetics (C/A, SH), MSD (SAB), Mersana (C/A, SH), eTheRNA immunotherapies NV (C/A, SH), Roche (travel expenses), Genmab (travel expenses), Amgen (travel expenses). Isabelle Ray-Coquard: Honoraria from AstraZeneca, Clovis, GSK/Tesaro and PharmaMar; Consulting/advisory board fees from AstraZeneca, Roche, Clovis, GSK/Tesaro, Genmab, PharmaMar, MSD, Mersana, Deciphera, OncXea, Esai, BMS, Novartis and Pfizer; Research funding from MSD;Travel expenses from AstraZeneca, GSK and Roche. Yakir Segev: AstraZeneca (CA), GSK (CA). Pauline Wimberger: Amgen (SH, RF, SAB), AstraZeneca (SH, RF, H, SAB), Clovis (SH, RF, SAB), Eisai (SH, SAB), GSK (SH, SAB), Lilly (SH, SAB), MSD (SH, RF, SAB), Novartis (SH, RF, SAB), Pfizer (SH, RF, SAB), Roche (SH, RF, H, SAB), TEVA (SH, SAB). Natalie YL Ngoi: AstraZeneca (SH), Janssen (SH). Kazuhiro Takehara: AstraZeneca (SH), Chugai (SH, RF), Eisai (SH), MSD (SH), Mochida (SH), Takeda (SH). Takayuki Enomoto: Takeda (SH), Astra Zeneca (SH), Eisai (SH), Chugai Pharma (SH, RF), MSD (SH), Mochida (SH). Domenica Lorusso: AstraZeneca (H, CA), Clovis (H, CA, RF), GSK/Tesaro (H, CA), Roche (CA), Genmab (CA), PharmaMar (CA, RF), MSD (CA, RF), Esai (CA), Merck Serono (CA), Novartis (CA) and PharmaMar (H); Consulting/advisory board fees from AstraZeneca, Roche, Clovis, GSK/Tesaro. Diane Provencher: AstraZeneca (CA, SH, SAB), GSK (CA, SH, SAB). Nadeem Abu-Rustum: NIH/NCI Cancer Center Support Grant P30 CA008748 (F). Hannelore Denys: Roche (CA, SH, SAB), Pfizer (CA, SH, SAB), AstraZeneca (SH, SAB), Lily (SAB), GSK (SAB), Novartis (SH), Pharmamar (SH). Bradley J Monk: AstraZeneca (SH, SAB), GSK (SH, SAB), Incyte (SAB), Merck (SH, SAB), Roche/Genentech (SH, SAB), Eisai (SAB), GOG-Foundation (E), US Oncology (E). The other authors indicated no financial relationship. Legend: consulting/advisory relationship (CA); speaker honoraria (SH); honoraria (H); research funding (RF); ownership interest (OI); intellectual propriety/patent holder (IP); scientific advisory board (SAB)., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Prospective data have demonstrated the efficacy of bevacizumab monotherapy in the treatment of advanced endometrial cancer. Bevacizumab is used off-label, and real-world data regarding the role of bevacizumab in endometrial cancer treatment are scant. In this largest single-institution retrospective study of its kind, we report our experience with bevacizumab monotherapy in the treatment of advanced/recurrent endometrial cancer., Methods: All eligible patients (n = 101) had histologically confirmed endometrial cancer and were treated with bevacizumab at our institution from 2004 to 2017. Demographic data and tumor characteristics were obtained through chart review. Primary objective was response to therapy determined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1)., Results: Analysis included 13 grade 1/2 endometrioid, 15 grade 3 endometrioid, 44 serous, 8 carcinosarcoma, and 21 other/mixed histologies. No patients achieved complete (CR) or partial (PR) responses; 19 achieved stable disease (SD). The clinical benefit rate (CBR; CR + PR + SD) was 19% (95% CI: 12-28%). The CBRs were 7%, 17%, 21%, and 23% for patients with 1, 2, 3, and ≥ 4 prior treatment lines. Median PFS ranged from 2.6 months (2 lines) to 4.9 months (≥4 lines). The 3-year OS rate was 58% (95% CI: 47-67%). The median OS was 3.4 years (95% CI: 2.9-4.2), ranging from 2.5 years (2 lines) to 4.5 years (≥4 lines). The most common treatment-related adverse event was hypertension; 35 (78%) of 45 were grade 1 or 2., Conclusions: In heavily pretreated advanced endometrial cancer, bevacizumab was associated with modest clinical efficacy and remains a viable palliative option in this setting., Competing Interests: Declaration of Competing Interest Outside the submitted work, Dr. Rubinstein reports a 2019 ASCO Young Investigator Award; Dr. Lakhman is a shareholder of Y-mAbs Therapeutics, Inc.; Dr. Iasonos reports consulting fees from Mylan; and Dr. Makker reports personal fees from ArQule, Eisai, Karyopharm, Merck, Clovis, and IBM Watson, as well as grants (institutional funding support) from Merck, Eisai, Karyopharm, AstraZeneca, Clovis, Moreo, Takeda, Genentech, and Zymeworks. The other authors have nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To characterize and compare the molecular subtypes and profiles of prospectively-accrued newly-diagnosed early- and advanced-stage endometrial cancers (ECs)., Methods: EC patients consented to an IRB-approved protocol of massively parallel sequencing of 410-468 cancer-related genes; 175 ECs of 7 histologic types (n = 135 FIGO stages I/II, n = 40 FIGO stages III/IV) were included. Previously reported sequencing data from 99 additional advanced-stage ECs were retrieved for comparisons., Results: Irrespective of histologic type, all 175 ECs could be stratified into the molecular subtypes, with 75 (43%) being of p53 wild-type, 49 (28%) MMR-deficient, 39 (22%) p53 abnormal and 12 (7%) of POLE molecular subtypes. Subtype distribution, mutational and copy number profiles varied according to histologic type. In endometrioid ECs, genetic alterations varied according to histologic grade. Potential therapeutic targets, including high tumor mutational burden, ERBB2 amplification and PIK3CA hotspot mutations, were found across histologic types in 63% (n = 110) of all ECs. Compared to their early-stage counterparts, advanced-stage endometrioid ECs had a significantly higher fraction of genome altered (median 0.1% vs 12%, p < 0.001) and ARID1B mutations (0% vs 11%, p = 0.01), and advanced-stage serous ECs harbored more frequent ERBB2 amplification (18% vs 8%, p > 0.05) and PIK3CA mutations (46% vs 27%, p > 0.05). Whole-genome doubling was found in advanced- but not early-stage carcinosarcomas and clear cell carcinomas., Conclusions: Our findings demonstrate the molecular heterogeneity within and across histologic types of EC and the increased genomic complexity of advanced-stage ECs. Molecular subtypes are present across EC histologic types and may help stratify EC patients for prognostic and therapeutic purposes., Competing Interests: Declaration of Competing Interest R.A. Soslow reports NIH grant funding. S. Chiang serves as a consultant for AstraZeneca, outside the scope of the submitted manuscript. J.S. Reis-Filho reports receiving personal/consultancy fees from Goldman Sachs, REPARE Therapeutics and Paige.AI, membership of the scientific advisory boards of VolitionRx, REPARE Therapeutics and Paige.AI, membership of the Board of Directors of Grupo Oncoclinicas, and ad hoc membership of the scientific advisory boards of Roche Tissue Diagnostics, Ventana Medical Systems, Novartis, Genentech and InVicro, outside the scope of this study. C.F. Friedman reports institutional research support from Bristol Myers Squibb, Merck, Astra Zeneca and Genentech as well as membership of the scientific advisory boards of Merck and Genentech, outside the scope of the submitted manuscript. D. Zamarin reports personal/consultancy fees from Merck, Synlogic Therapeutics, Xencor, Biomed Valley Discoveries, Trieza Therapeutics, Tesaro, and Agenus, outside of the scope of this work. D. Zamarin reports institutional research support from Astra Zeneca, Plexxikon, and Genentech, outside of the scope of this work. V. Makker reports study funding from Merck, Eisai, Karyopharm, AstraZeneca, Clovis, Takeda, Lilly and Genentech, and honoraria/consultancy fees from Merck, Eisai, Karyopharm and Clovis, all outside the scope of this study. M.M. Leitao Jr. reports personal fees from JnJ/Ethicon and is an ad hoc speaker for Intuitive Surgical, Inc., outside the submitted work. N.R. Abu-Rustum reports institutional research grants from GRAIL and Stryker, outside the submitted work. C. Aghajanian reports grant support by Clovis, Genentech, AbbVie, AstraZeneca, and personal/ advisory board fees from Tesaro, Immunogen, Clovis, Eisai/Merck, Mersana Therapeutics, Roche/ Genentech, Abbvie, AstraZeneca, all outside the scope of the submitted manuscript. B. Weigelt reports membership of the ad hoc scientific advisory board of REPARE Therapeutics, outside the submitted work. The remaining authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Selinexor, a selective inhibitor of nuclear export, monotherapy causes nuclear accumulation of tumor-suppressor proteins and has anti-tumor activity in ovarian and endometrial cancers. The safety and tolerability of oral selinexor plus intravenous carboplatin and paclitaxel chemotherapy (selinexor + CP) was evaluated in this population., Patients and Methods: This phase I, 3 + 3 dose-escalation study assessed 4 selinexor + CP regimens. Patients in cohorts of 3, regardless of disease type, were administered 1 of 4 alternating regimens (selinexor at 30 mg/m 2 or 60 mg plus CP at AUC 5 and 175 mg/m 2 or 80 mg/m 2 , respectively) for 6-10 cycles (1 cycle = 21 days), followed by selinexor maintenance. Enrolled patients with ovarian cancer had received 1 prior platinum-based therapy. Patients with endometrial cancer were chemotherapy-naive or had received 1 prior platinum-based therapy. Response was evaluated every 9 weeks., Results: Twenty-three patients were treated (5 serous ovarian cancer; 18 endometrial cancer, including 6 carcinosarcomas). The most common treatment-related adverse events (TRAEs) were thrombocytopenia (100%), leukopenia (91%), and hyperglycemia (87%). The most common grade 3/4 TRAEs were leukopenia (70%), neutropenia (70%), lymphopenia (61%), anemia (57%), and alanine transaminase increase (43%). One treatment-related dose-limiting toxicity (grade 3 syncope) occurred. Twelve patients achieved a partial response and 1 achieved a complete response. Responses to all four regimens were observed in ovarian and endometrial cancers., Conclusions: Combination selinexor + CP was safe and tolerated in advanced ovarian and endometrial cancers., Competing Interests: Declaration of Competing Interest C. Aghajanian reports personal fees from Tesaro, Immunogen, Clovis, Mateon Therapeutics, Eisai/Merck, Mersana Therapeutics, and Roche, as well as grants from Clovis, Genentech, AbbVie, and AstraZeneca. K. Cadoo reports travel/expenses and institutional support from AstraZeneca, institutional support from Syndax Pharmaceuticals, as well as personal fees and travel/expenses from Tessaro and personal fees from OncLive. C. F. Friedman reports steering committee funding (compensation waived, research financial support to institution) from Genentech and Merck, institutional support from Bristol Myers Squibb, and personal fees from AstraZeneca. R. N. Grisham reports personal fees from Clovis, Mateon, Regeneron, Verastem, Amgen, and Medscape, as well as grant funding from Conquer Cancer Foundation (Career Development Grant supported by Amgen). R.N. Grisham has also received academic grants from Cycle for Survival, OCRFA and Kaleidoscope of Hope. A. Iasonos reports personal fees from Mylan, Intelligencia, and Brightpath. V. Makker reports grant funding from Karyopharm for the study described (Study PI: #14–110); grant funding from Eisai, Merck, Takeda, Karyopharm, AstraZeneca, Eli Lilly, Bristol Myers Squibb, and Genentech; and personal fees from Eisai, Merck, ArQule, Karyopharm, and IBM Watson. R. E. O'Cearbhaill reports personal fees from Tesaro, GlaxoSmithKline, and Clovis, and she is a non-compensated steering committee member for the PRIMA (niraparib) study and DUO-O (olaparib) study. M. M. Rubinstein reports grant funding from Conquer Cancer Foundation/American Society of Oncology. H. Xu reports non-financial support as a full-time employee (stock options) from Karyopharm. D. Zamarin reports personal fees from Merck, Agenus, Hookipa Biotech, and Western Oncolytics, grants from Merck, sponsored travel from Genentech, and stock options from Calidi Biotherapeutics. All other authors declare no potential conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: We assessed the safety and maximum tolerated dose (MTD) of the poly ADP-ribose polymerase (PARP) inhibitor olaparib with intravenous (IV)/intraperitoneal (IP) cisplatin/paclitaxel and IV bevacizumab, followed by olaparib and bevacizumab maintenance, in patients with newly diagnosed ovarian cancer who had undergone primary debulking surgery., Methods: Treatment included: (Cycles 1-6) Day 1, IV paclitaxel 135 mg/m 2 /3 h + (from Cycle 2 onward) bevacizumab 15 mg/kg; Day 2, IP cisplatin 75 mg/m 2 ; Days 2-8, olaparib (50/100/200 mg BID); Day 8, IP paclitaxel 60 mg/m 2 of a 21-day cycle. Maintenance (Cycles 7-22) included: olaparib 300 mg BID and bevacizumab 15 mg/kg Day 1. The primary endpoint was MTD of olaparib, chemotherapy, and bevacizumab., Results: Seventeen women were treated (Cohort 1 [50 mg olaparib], 8 patients; Cohort 2 [100 mg], 3 patients; and Cohort 3 [200 mg], 6 patients). Median age was 57 years (47-73); 94% had stage III disease; 29% had a germline BRCA mutation. Two of 6 patients in Cohort 3 experienced a dose-limiting toxicity (DLT). Grade 3/4 toxicities included: neutropenia (56%), lymphopenia (31%), anemia (25%), and fatigue (19%). Most patients started (88%, 81%) and completed (75%, 50%) maintenance olaparib and bevacizumab, respectively; 36% of patients on olaparib maintenance required a dose reduction. Median PFS was 33 months (26.2-NA)., Conclusions: The MTD of intermittently dosed olaparib with concurrent IV/IP cisplatin/paclitaxel and bevacizumab is 100 mg BID. Non-hematologic toxicities were predominantly low grade. One-third of patients on olaparib maintenance required dose reduction., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: Assess outcomes of a clinical cohort of patients with endometrioid endometrial cancer (EEC) harboring somatic POLE exonuclease domain mutations (EDMs)., Methods: Patients were consented to a protocol of tumor-normal massively parallel sequencing of 410-468 cancer related genes. EECs subjected to sequencing from 2014 to 2018 were reviewed. Tumors with somatic POLE EDMs were identified. EECs were assessed for microsatellite instability (MSI) using MSIsensor and immunohistochemical analysis for mismatch repair (MMR) proteins., Results: Of the 451 EECs sequenced, 23 had a POLE EDM (5%): 20 primary and 3 recurrent tumors sequenced. Nineteen cases (83%) were stage I/II and 4 (17%) were stages III/IV. Thirteen EECs (57%) were of FIGO grades 1/2, 10 (43%) grade 3. All patients were treated with surgery and 17 (89%) received adjuvant therapy. Five (22%) demonstrated loss of DNA MMR protein expression, none were due to Lynch syndrome. MSIsensor scores were conclusive for 21 samples: 19 were microsatellite stable and 2 MSI-high. After median follow-up of 30 months, 4/23 (17%) developed recurrences: 3 with initial grade 3 stage I and 1 with grade 1 stage III disease. One patient with grade 2 stage IV EEC had progressive disease after treatment., Conclusions: Patients with POLE EDM EEC have been shown to have a favorable prognosis. In this real-world cohort of patients, de novo metastatic disease and recurrences in initially uterine-confined cases were observed. Further research is warranted before incorporating the presence of POLE EDM into decision-making regarding adjuvant therapy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To evaluate clinical outcomes of patients with BRCA-associated ovarian cancer who developed brain metastases (BM)., Methods: Patients with epithelial ovarian, fallopian tube, and primary peritoneal cancer (EOC) and BM, treated at a single institution from 1/1/2008-7/1/2018, were identified from two institutional databases. Charts and medical records were retrospectively reviewed for clinical characteristics and germline BRCA mutation status. Appropriate statistics were used., Results: Of 3649 patients with EOC, 91 had BM (2.5%). Germline mutation status was available for 63 (69%) cases; 21 (35%) of these harbored a BRCA1/2 mutation (15 BRCA1, 6 BRCA2). Clinical characteristics were similar between groups. BM were diagnosed at a median of 31 months (95% CI, 22.6-39.4) in BRCA-mutated (mBRCA) and 32 months (95% CI, 23.7-40.3) in wild-type BRCA (wtBRCA) (p = 0.78) patients. Brain metastases were the only evidence of disease at time of BM diagnoses in 48% (n = 10) mBRCA and 19% (n = 8) wtBRCA (p = 0.02) patients. There was no difference in treatment of BM by mutation status (p = 0.84). Survival from time of BM diagnosis was 29 months (95%CI, 15.5-42.5) in mBRCA and 9 months (95% CI, 5.5-12.5) in wtBRCA patients, with an adjusted hazard ratio (HR) of 0.53, p = 0.09; 95% CI, 0.25-1.11. HR was adjusted for presence of systemic disease at time of BM diagnosis., Conclusion: This is the largest study to date comparing outcomes in patients with EOC and BM by mutation status. mBRCA patients were more likely to have isolated BM, which may be a factor in their long survival. This supports the pursuit of aggressive treatment for mBRCA EOC patients with BM. Additional studies examining the correlation of BRCA mutational status with BM are warranted., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Cabozantinib is a receptor tyrosine kinases inhibitor that targets MET (c-MET), VEGF receptor 2 (VEGFR2), RET, AXL, KIT, FLT-3, and TIE-2 and previously showed promising single agent activity in recurrent ovarian cancer., Methods: This was an open label, 1:1 randomized study of cabozantinib 60 mg orally (PO) daily versus weekly paclitaxel 80 mg/m 2 given 3 out of 4 weeks (NCT01716715); 111 patients were enrolled. Eligibility included persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma and at least one but no >3 prior chemotherapy regimens., Results: Median PFS was similar for both treatment groups and was 5.3 months for cabozantinib and 5.5 months for weekly paclitaxel (HR 1.11 (90% CI 0.77-1.61, p = 0.64)). Secondary analyses of overall survival (OS) and event free survival (EFS) showed that cabozantinib did not perform as well as weekly paclitaxel. Median OS for cabozantinib was 19.4 months and was not reached for weekly paclitaxel (HR 2.27 (90% CI 1.17-4.41, p = 0.04). EFS was also worse in the cabozantinib arm, 3.5 months, compared to weekly paclitaxel at 5.0 months (HR 1.81 (90% CI 1.24-2.63, p = 0.01). Overall response rate (ORR) was less for cabozantinib compared to weekly paclitaxel (7% versus 24.1%). Gastrointestinal toxicities, specifically nausea, diarrhea, and abdominal pain were worse in the cabozantinib arm., Conclusions: Median PFS was similar for cabozantinib and weekly paclitaxel. However, OS, EFS, and ORR were worse for cabozantinib compared to weekly paclitaxel. Cabozantinib given at this dose and schedule cannot be recommended as a treatment for recurrent ovarian cancer., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Delayed responses observed with immune checkpoint blockade (ICB) present a challenge for patients with peritoneal malignancies, who risk early symptomatic disease progression requiring treatment discontinuation. While efforts are ongoing to define the biomarkers of response, it is equally important to identify patients at risk for early discontinuation. We sought to investigate the timing of disease progression in epithelial ovarian cancer (EOC) patients treated with ICB and to identify pre-treatment clinical parameters associated with early discontinuation., Methods: Retrospective analysis was performed on EOC patients treated with ICB at MSKCC from January 2013 to May 2017. Cutoffs for early and very early discontinuation due to disease progression were defined at 12 and 8 weeks, respectively. Univariate and multivariate logistic regression models were built based on pre-treatment clinical variables., Results: Of 108 identified patients, 89 were included in the analysis. Forty-six (51.7%) patients discontinued therapy early, 30 of which (33.7%) discontinued therapy very early. Eight patients (9.0%) died within 12 weeks of ICB initiation from disease progression. In multivariate analyses, bulky peritoneal disease (p = 0.009, OR: 4.94) and liver parenchymal metastases (p = 0.001, OR: 8.08) were associated with early discontinuation. Liver parenchymal metastases (p = 0.001, OR 6.64), and high neutrophil-to-lymphocyte ratio (p = 0.021, OR: 3.54), were associated with very early discontinuation., Conclusions: Over 50% of EOC patients suffer disease progression requiring early discontinuation of ICB. Pre-treatment prognostic clinical characteristics may identify patients at highest risk for early discontinuation due to disease progression and warrant caution in using these agents in late line patients with advanced disease., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the rates and distribution of first recurrence in patients with FIGO stage IIIC1 endometrial cancer (EC) who did not undergo paraaortic dissection at surgical staging., Methods: We retrospectively selected all (n = 207) stage IIIC1 patients treated at a single institution from 5/1993-1/2017. Sites of first recurrence were identified, disease-free (DFS) and overall survival (OS) calculated, multivariate logistic regression performed to identify factors associated with recurrence., Results: Three-year DFS and OS were 66.5% and 85.7%, respectively. The most common histology was endometroid (64.2%). Three-year DFS was 81% (SE±3.8%) endometrioid vs. 39.5% (SE±6.6%) non-endometrioid (P < 0.001). Three-year OS was 96.9% (SE±1.8%) endometrioid vs. 65.6% (SE±6.7%) non-endometrioid (P < 0.001). Sixty-two (30.1%) patients recurred. Patterns of recurrence were: 14 (8.3%) multiple sites, 17 (8.2%) abdominal, 14 (6.8%) extra-abdominal, 17 (8.3%) isolated nodal (8 of these (3.9%) paraaortic). Patients with isolated tumor cells (ITCs) in lymph nodes only had 12/71 (17%) recurrence rate vs. 50/135 (37%) for patients with micro-/macrometastasis. On univariate analysis, grade (HR 4.67 95%CI 1.5-14.5, P = 0.008), histology (HR 4.9 95%CI 2.6-9.3, P < 0.001), myometrial invasion (HR 1.9 95%CI 1.04-3.5, P = 0.04), pelvic washing (HR 2.2 95%CI 1.1-4.5, P = 0.03), tumor volume in pelvic LNs (ITC vs. micro-/macrometastasis; HR 0.3 95%CI 0.2-0.7, P = 0.003) were associated with recurrence. On multivariate analysis, only histology was associated with recurrence (HR 7.88 95%CI 3.43-18.13, P < 0.001)., Conclusions: Isolated paraaortic recurrence in stage IIIC1 EC is uncommon. Micro-/macrometastasis were associated with twice the recurrence rate compared to ITC. These data will help clinicians counsel patients with stage IIIC1 EC regarding paraaortic assessment., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: To compare oncologic outcomes in the staging of deeply invasive endometrioid endometrial carcinoma (EEC) using a sentinel lymph node algorithm (SLN) versus pelvic and paraaortic lymphadenectomy to the renal veins (LND); to compare outcomes in node-negative cases., Methods: At two institutions, patients with deeply invasive (≥50% myometrial invasion) EEC were identified. One institution used LND (2004-2008), the other SLN (2005-2013). FIGO stage IV cases were excluded. Clinical characteristics and follow-up data were recorded., Results: 176 patients were identified (LND, 94; SLN, 82). SLN patients were younger (p = 0.003) and had more LVSI (p < 0.001). 9.8% in the SLN and 29.8% in the LND cohorts, respectively, received no adjuvant therapy (p < 0.001). There was no association between type of assessment and recurrence; adjusted hazard ratio (aHR; LND vs. SLN) 0.87 (95%CI 0.40, 1.89) PFS. After controlling for age and adjuvant therapy, there was no association between assessment method and OS (aHR 2.54; 95%CI 0.81, 7.91). The node-negative cohort demonstrated no association between survival and assessment method: aHR 0.69 (95%CI 0.23, 2.03) PFS, 0.81 (95%CI 0.16, 4.22) OS. In the node-negative cohort, neither adjuvant EBRT+/-IVRT (HR 1.63; 95%CI 0.18, 14.97) nor adjuvant chemotherapy+/-EBRT+/-IVRT (HR 0.49; 95%CI 0.11, 2.22) were associated with OS, compared to no adjuvant therapy or IVRT-only., Conclusion: Use of an SLN algorithm in deeply invasive EEC does not impair oncologic outcomes. Survival is excellent in node-negative cases, irrespective of assessment method. Adjuvant chemotherapy in node-negative patients does not appear to impact outcome., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To determine the efficacy of dalantercept, a soluble ALK1 inhibitor receptor fusion protein, in patients with persistent or recurrent ovarian carcinoma and related malignancies., Methods: Eligibility criteria included measurable disease, 1-2 prior cytotoxic regimens and GOG performance status (PS) ≤2. Dalantercept was administered subcutaneously at 1.2 mg/kg every 3 weeks until disease progression or development of unacceptable toxicity. The primary null hypothesis was the probability of response ≤0.10 and the probability of 6-month progression-free survival without receipt of non-protocol therapy (event-free survival at 6 months, EFS6) ≤0.15, using RECIST 1.1 criteria., Results: The first stage was closed after enrollment of 30 participants with median age of 56.5 years, high-grade serous histology in 76.7%, 2 prior regimens in 46.7%, and platinum-free interval <6 months in 73.3%. All participants discontinued dalantercept, 24 (80.0%), 5 (16.7%) and 1 (3.3%) due to progression, toxicity, and other reason, respectively. The median number of treatment cycles per patient was 2 (range 1-29). There were six treatment-related grade 3 AEs and no grade ≥4 AEs. There were no objective responses. EFS6 was reached in 20% (6 out of 30 participants, 90% CI 9.1% to 35.7%)., Conclusions: Though safe, dalantercept as administered had limited efficacy in this patient population overall., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Rapamycin analogs have reproducible but modest efficacy in endometrial cancer (EC). Identification of molecular biomarkers that predict benefit could guide clinical development., Methods: Fixed primary tissue and whole blood were collected prospectively from patients enrolled on GOG 248. DNA was isolated from macro-dissected tumors and blood; next-generation sequence analysis was performed on a panel of cancer related genes. Associations between clinical outcomes [response rate (RR) 20%; progression-free survival (PFS) median 4.9months] and mutations (PTEN, PIK3CA, PIK3R1, KRAS, CTNNB1, AKT1, TSC1, TSC2, NF1, FBXW7) were explored., Results: Sequencing data was obtained from tumors of 55 of the 73 enrolled pts. Mutation rates were consistent with published reports: mutations in PTEN (45%), PIK3CA (29%), PIK3R1 (24%), K-RAS (16%), CTNNB1 (18%) were common and mutations in AKT1 (4%), TSC1 (2%), TSC2 (2%), NF1 (9%) and FBXW7 (4%) were less common. Increased PFS (HR 0.16; 95% CI 0.01-0.78) and RR (response difference 0.83; 95% CI 0.03-0.99) were noted for AKT1 mutation. An increase in PFS (HR 0.46; 95% CI 0.20-0.97) but not RR (response difference 0.00, 95% CI -0.34-0.34) was identified for CTNNB1 mutation. Both patients with TSC mutations had an objective response. There were no statistically significant associations between mutations in PIK3CA, PTEN, PIK3R1, or KRAS and PFS or RR., Conclusions: Mutations in AKT1, TSC1 and TSC2 are rare, but may predict clinical benefit from temsirolimus. CTNNB1 mutations were associated with longer PFS on temsirolimus., (Copyright © 2016. Published by Elsevier Inc.)

Objective: This two-stage phase II study assessed activity of single agent dalantercept in patients with recurrent/persistent endometrial carcinoma (EMC)., Methods: Eligible patients had persistent/recurrent EMC after 1-2 prior cytotoxic regimens, measurable disease (RECIST 1.1), and GOG performance≤2. Dalantercept 1.2mg/kg subcutaneous was administered once every 3weeks until disease progression (PD)/development of prohibitory toxicity. Primary objectives were to estimate the proportion of patients with persistent/recurrent EMC, who survive progression-free without receiving non-protocol therapy (TPFS) for at least 6months and to estimate the proportion having objective tumor response., Results: All 28 enrolled patients were eligible and evaluable. Median age: 62years. Most common histologies: 32% Grade 1/2 endometrioid and 54% serous tumors. Prior treatment: 1 or 2 regimens in 82% and 18% of patients, respectively. Eighteen patients received prior radiation therapy. Patients received 1-12 cycles of dalantercept, and 46% of patients received ≤2cycles. The most common adverse events (AE) were fatigue, anemia, constipation and peripheral edema. Grade 3/4 AEs occurred in 39% and 4% of patients. One grade 5 gastric hemorrhage in a patient with a history of radiation fibrosis/small bowel obstruction was deemed possibly dalantercept-related. All patients are off study: 86% for PD. No ORs were observed; 57% had stable disease and 11% had TPFS>6 mos. Median progression-free and overall survival: 2.1months (90% CI: 1.4-3.2) and 14.5months (90% CI: 7.0-17.5), respectively., Conclusions: Dalantercept has insufficient single agent activity in recurrent EMC to warrant further investigation at this dose level and schedule., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To assess whether contemporary adjuvant management of early stage uterine carcinosarcoma (CS) produces equal outcomes as in uterine serous carcinoma (USC)., Methods: We reviewed 172 women treated from 2000 to 2011 for stage I-II USC (n=112, 65%) or CS (n=60, 35%). Adjuvant therapy was initiated in 154 (90%) patients, with 111 patients receiving intravaginal radiotherapy (IVRT)/chemotherapy. Median follow up was 4.6 years for surviving patients., Results: Characteristics for USC vs. CS did not differ significantly by age ≥60, pelvic or para-aortic node sampling, stage, lymphovascular invasion, chemotherapy use, RT use or omission of adjuvant therapy. Outcomes were better for USC vs. CS in 5-year actuarial rates of recurrence [17% (C.I. 10-25%) vs. 45% (C.I. 31-59%), p<0.001],disease-related mortality (DRM) [11% (5-17%) vs. 30% (16-44%), p=0.016], and all-cause mortality [12% (C.I. 6-18%) vs. 34% (C.I. 20-48%), p=0.007]. In multivariable analysis, CS histology remained a significant predictor of risk for recurrence [HR 3.1 (C.I. 1.7-5.7), p<0.001], DRM [HR 2.4 (C.I. 1.1-5.1), p=0.024], and all-cause mortality [HR 2.4 (C.I. 1.2-4.8), p=0.012]. On sub-group analysis of 111 patients (77 USC, 34 CS) able to receive IVRT/chemotherapy, CS no longer was associated significantly with increased recurrence (29% vs. 15%, p=0.18), DRM (22% vs. 10%, p=0.39), or all-cause mortality (22% vs. 10%, p=0.45)., Conclusions: CS was associated with worse outcomes than USC. However, that difference was not maintained in patients able to receive IVRT and chemotherapy. While intriguing, this result may be due in part to selection against rapid early relapsing CS patients in this group., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: To determine the response, toxicities, and progression free survival of a regimen of temsirolimus with or without hormonal therapy in the treatment of advanced, or recurrent endometrial carcinoma., Background: Preclinical evidence suggested that blockade of the PI3K/AKT/mTOR pathway might overcome resistance to hormonal therapy., Methods: We performed a randomized phase II trial of intravenous temsirolimus 25mg weekly versus the combination of weekly temsirolimus with a regimen of megestrol acetate 80 mg bid for three weeks alternating with tamoxifen 20mg bid for three weeks in women with recurrent or metastatic endometrial carcinoma., Results: There were 71 eligible patients who received at least one dose of therapy with 21 of these treated on the combination arm which was closed early because of an excess of venous thrombosis, with 5 episodes of deep venous thrombosis (DVT) and 2 pulmonary emboli. There were three responses observed in that arm (14%). A total of 50 eligible patients were treated on the single agent arm with 3 episodes of DVT and 11 responses (22%). Response rates were similar in patients with prior chemotherapy (7 of 29; 24%) and those with no prior chemotherapy (4 of 21; 19%). Two of four patients with clear cell carcinoma responded., Conclusions: Adding the combination of megestrol acetate and tamoxifen to temsirolimus therapy did not enhance activity and the combination was associated with an excess of venous thrombosis. Temsirolimus activity was preserved in patients with prior adjuvant chemotherapy., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To evaluate patterns of relapse in early stage uterine papillary carcinoma (UPSC) patients receiving adjuvant intravaginal radiotherapy (IVRT) with or without chemotherapy., Methods: From 1/1996 to 12/2010, 77 women with stage I-II UPSC underwent surgery followed by IVRT (median 21Gy). Stage IA patients without residual disease at surgery were excluded. IVRT and chemotherapy (carboplatin/taxane) was given to 61 (79%) patients and IVRT alone to 16 (21%). The median follow-up was 62 months for surviving patients., Results: Of the 77 patients, 11 (14%) relapsed as follows: vaginal 2 (3%), pelvic 5 (6%), para-aortic 5 (6%), peritoneal 6 (8%), and other distant sites 8 (10%). Of the 5 pelvic relapses, 2 were isolated and were salvaged. In those treated without chemotherapy, only 1/16 developed recurrence (mediastinal). The 5-year vaginal, pelvic, para-aortic, peritoneal, and distant recurrence rates were 2.7% (C.I. 0-6.2%), 5.8% (C.I. 0.6-11.0%), 5.4% (C.I. 0.6-10.1%), 5.3% (C.I. 0.5-10.1%) and 6.6% (C.I. 1.4-11.8%), respectively. The 5-year disease-free survival (DFS), and overall survival (OS) were 88% (C.I. 81-95%), and 91% (C.I. 84-97%), respectively. The only predictor of worse 5-year pelvic control was stage (96.2% stage IA vs 87.7% for stage IB-II, p=0.043)., Conclusions: In stage I-II UPSC patients who predominantly receive adjuvant chemotherapy, IVRT as the sole form of adjuvant RT provides excellent locoregional control. The risk of isolated pelvic recurrence is too low to warrant routine use of external pelvic RT., (© 2013.)

Objective: To report the incidence of nodal metastases in patients presenting with presumed low-grade endometrioid adenocarcinomas using a sentinel lymph node (SLN) mapping protocol including pathologic ultrastaging., Methods: All patients from 9/2005 to 12/2011 who underwent endometrial cancer staging surgery with attempted SLN mapping for preoperative grade 1 (G1) or grade 2 (G2) tumors with <50% invasion on final pathology, were included. All lymph nodes were examined with hematoxylin and eosin (H&E). Negative SLNs were further examined using an ultrastaging protocol to detect micrometastases and isolated tumor cells., Results: Of 425 patients, lymph node metastasis was found in 25 patients (5.9%) on final pathology-13 cases on routine H&E, 12 cases after ultrastaging. Patients whose tumors had a DMI <50% were more likely to have positive SLNs on routine H&E (p<0.005) or after ultrastaging (p=0.01) compared to those without myoinvasion., Conclusions: Applying a standardized SLN mapping algorithm with ultrastaging allows for the detection of nodal disease in a presumably low-risk group of patients who in some practices may not undergo any nodal evaluation. Ultrastaging of SLNs can likely be eliminated in endometrioid adenocarcinoma with no myoinvasion. The long-term clinical significance of ultrastage-detected nodal disease requires further investigation as recurrences were noted in some of these cases., (© 2013.)

Objectives: According to the updated FIGO system, positive peritoneal cytology does not affect endometrial cancer stage. This revision may reduce rates of obtaining cytology, with unclear implications in advanced disease. This study evaluates the significance of positive cytology in stage III (FIGO 2009) endometrial cancer., Methods: Eligible patients received treatment for stage III endometrial cancer at a single institution and had peritoneal cytology performed., Results: Of 196 patients, 58% were ≥ 60 years old, 48% had deep myometrial invasion, 71% lymphovascular invasion, 25% cervical invasion, 37% adnexal involvement, 79% nodal involvement, and 46% aggressive histology. Positive cytology was present in 23% (45/196) and significantly associated with cervical stromal invasion, adnexal involvement, and aggressive histology (P ≤ 0.03). There was no significant difference in rates of lymphadenectomy, chemotherapy, or radiation between negative and positive cytology groups. At a median follow-up of 47 months, the 5-year freedom from relapse was 39% for positive cytology vs. 69% for negative, disease-specific survival 42% vs. 77%, and overall survival 34% vs. 72% (P < 0.001). Positive cytology correlated with higher recurrence rates in the para-aortic nodes and peritoneum (30% vs. 9%, 23% vs. 4%; P ≤ 0.008). When controlling for adverse features including aggressive histology, positive cytology was associated with an increased hazard for relapse (HR 2.3; P = 0.002) and death (HR 2.9; P < 0.001)., Conclusions: In stage III endometrial cancer, positive cytology independently predicts outcome and is associated with distinct relapse patterns. Obtaining peritoneal cytology in stage III endometrial cancer is critical., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: Placental-site trophoblastic tumor (PSTT) is the rarest form of gestational trophoblastic disease (GTD). A risk-adapted treatment approach has been advocated, but controversy exists as to the most important prognostic markers for this disease. Our goal was to determine the prognostic markers for patients with PSTT seen at our center., Methods: We conducted a retrospective analysis of patients with PSTT seen at a single tertiary care center between 1996 and 2011. The association of FIGO stage, interval from antecedent pregnancy, antecedent pregnancy outcome, human chorionic gonadotropin (hCG) level, and age to overall survival was examined using univariate log-rank tests. Presentation, treatment, and outcome were summarized using descriptive statistics., Results: Data from 17 patients were analyzed. Eight (47%) had Stage I/II disease and 9 (53%) had Stage III/IV disease. Median overall survival for the entire cohort was 86 months (range, 2-101 months). Median duration of follow-up for surviving patients was 56 months. Increasing FIGO stage (I-III versus IV) was associated with a worse overall survival (p=0.009). Interval from antecedent pregnancy (≥12months), antecedent pregnancy outcome (full-term), hCG (≥1000 IU/L), and age (≥40) were not associated with worse survival., Conclusion: FIGO stage, specifically Stage IV disease, was the most important predictor of overall survival in our cohort of PSTT patients., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: Little prospective data exist on quality of life (QOL) after pelvic exenteration (PE). This ongoing study prospectively examines the QOL changes following this radical procedure using a comprehensive battery of psychological instruments., Methods: Since 2005, enrolled patients were interviewed (EORTC QLQ-C30, EORTC QLQ-CR38, EORTC QLQ-BLM30, BFI, BPI-SF, IADL, CES-D, IES-R) preoperatively and at 3, 6, and 12 months after PE for physical/psychological symptoms. Data were examined using repeated measure ANOVA., Results: Sixteen women (3 anterior, 1 posterior, and 12 total PEs), with more than 1 year of follow-up, completed all scheduled interviews. Median age was 58 years (range, 28-76 years). Overall QOL (F = 6.3, p < 0.02), ability to perform instrumental daily activities (F = 6.8, p < 0.02), body image (F = 11.9, p < 0.00), and sexual function (F = 8.0, p < 0.01) all declined at 3 months but were near baseline by 12 months after PE. Although, overall, physical function followed a similar trend (F = 14.8, p < 0.00), it did not return to baseline. At the 12-month interview, patients reported increased gastrointestinal symptoms (F = 8.9, p < 0.01) but significantly less stress-related ideation (F = 6.1, p < 0.03) compared to baseline. Pain levels did not change significantly during the study period (F = 0.4, p < 0.74)., Conclusions: Although patients report lingering gastrointestinal symptoms and some persistent decline in physical function after PE, most adjust well, returning to almost baseline functioning within a year. Providers can counsel patients that many, though not all, symptoms in the first 3 months following exenteration are likely to improve as they adapt to their changed health status. These preliminary results await confirmation of a larger analysis., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: According to national surveys, the use of intensity-modulated radiation therapy (IMRT) in gynecologic cancers is on the rise, yet there is still some reluctance to adopt adjuvant IMRT as standard practice. The purpose of this study is to report a single-institution experience using postoperative pelvic IMRT with concurrent chemotherapy in intermediate- and high-risk early stage cervical cancer., Methods: From 1/2004 to 12/2009, 34 patients underwent radical hysterectomy and pelvic lymph node dissection (28 median nodes were removed) for early stage cervical cancer. Median dose of postoperative pelvic IMRT was 50.4 Gy (range, 45-50.4). All patients received concurrent cisplatin., Results: With a median follow-up of 44 months, 3 patients have recurred; 1 vaginal recurrence, 1 regional and distant, and 1 distant. The 3- and 5-year disease-free survival (DFS) was 91.2% (95% CI, 81.4-100%) and overall survival (OS) was 91.1% (95% CI, 81.3-100%). All failures and all deaths were in the high-risk group (n=3/26). There was 32.3% G3-4 hematologic toxicity, 2.9% acute G3 gastrointestinal toxicity, and no acute G3 or higher genitourinary toxicity. There were no chronic G3 or higher toxicities., Conclusions: Oncologic outcomes with postoperative IMRT were very good, with DFS and OS rates of >90% at median follow-up of 44 months, despite a preponderance (76.5%) of high-risk features. Toxicity was minimal even in the setting of an aggressive trimodality approach. Data from this study and emerging data from the Phase II RTOG study (0418) demonstrate the advantages of postoperative IMRT in early stage cervical cancer., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: The purpose of this study is to report our single-institution experience with concurrent adjuvant intravaginal radiation (IVRT) and carboplatin/paclitaxel chemotherapy for early stage uterine papillary serous carcinoma (UPSC)., Methods: From 10/2000 to 12/2009, 41 women with stage I-II UPSC underwent surgery followed by IVRT (median dose of 21 Gy in 3 fractions) and concurrent carboplatin (AUC=5-6) and paclitaxel (175 mg/m(2)) for six planned cycles. IVRT was administered on non-chemotherapy weeks. The Kaplan-Meier method was used to estimate survival, and the log-rank test was used for comparisons., Results: Median patient age was 67 years (51-80 years). Surgery included hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, omental biopsy, and pelvic and paraaortic lymph node sampling. FIGO 2009 stage was IA in 73%, IB in 10%, and II in 17%. Histology was pure serous in 71% of cases. Thirty-five patients (85%) completed all planned treatment. With a median follow-up time of 58 months, the 5-year disease-free (DFS) and overall survival (OS) rates were 85% (95%CI, 73-96%) and 90% (95%CI, 80-100%). The 5-year pelvic, para-aortic, and distant recurrence rates were 9%, 5%, and 10%, respectively. There were no vaginal recurrences. Of the 4 pelvic recurrences, 2 were isolated and were successfully salvaged. Patients with stage II disease had lower DFS (71% vs. 88%; p=0.017) and OS (71% vs. 93%; p=0.001) than patients with stage I disease., Conclusions: Concurrent adjuvant carboplatin/paclitaxel chemotherapy and IVRT provide excellent outcomes for early stage UPSC. Whether this regimen is superior to pelvic radiation will require confirmation from the ongoing randomized trial., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To report a single institution experience in surgical stage I-II serous endometrial cancer using combined carboplatin/paclitaxel and intravaginal radiation (IVRT)., Methods: Between 10/00 and 12/06, 25 stage I-II patients with serous endometrial cancer were treated at our institution with surgery, postoperative IVRT, and concurrent chemotherapy (CT)., Results: The mean age was 67 years old (range, 53-80 years). Surgery consisted of hysterectomy (TAH/BSO, 64%, LAVH/BSO, 36%), peritoneal washing, omental biopsy, and pelvic lymph-node dissection (median 14 nodes). Para-aortic node sampling was done in 88% (median, 6). IVRT median dose was 21 Gy (range, 18-21 Gy, in 3 fractions) and concurrent CT consisted of carboplatin to AUC=5 and taxol to 175 mg/m(2) given every 3 weeks for 6 cycles. CT was well tolerated with 22/25 (88%) receiving 6 cycles. Three patients received

Purpose: To determine the progression-free survival (PFS) and overall survival (OS) in a cohort of patients who received either platinum-based chemotherapy with or without radiation therapy (pelvic or WAI), or RT alone., Methods: Memorial Sloan-Kettering Cancer Center (MSKCC) electronic medical records from 8/1/1995 to 10/3/2007 were reviewed for patient age, diagnosis date, type of primary surgery, residual disease at the completion of primary surgery, FIGO stage, treatment details, dates of progression and death, and site(s) of first recurrence. PFS and OS by stage (I/II v III/IV) and by treatment type (chemotherapy with or without RT v RT alone) were determined using landmark analyses 8 weeks after surgery. Patients who received chemotherapy with or without RT (pelvic or abdominal) or RT alone (pelvic or abdominal) were included in the analysis. Both groups were allowed to have received intravaginal radiation therapy (IVRT)., Results: Forty-nine patients met study criteria. Thirty-eight/49 patients received chemotherapy: 23/38 (60.5%) received paclitaxel-carboplatin; 7/38 (18.4%) received ifosfamide-platinum; 8/38 (21.0%) received other chemotherapy. FIGO stage was: I=15 (31%); II=5 (10%); III=21 (43%); IV=8 (16%). Three-year PFS for the entire cohort was 24%. Three-year OS for the entire cohort was 60%. Three-year median PFS time for the entire cohort was 15 months (95% CI: 11-25 months). Three-year median OS time for the entire cohort was 67 months (95% CI: 23-89 months). Three-year PFS for stages I-II was 43% v 14% for stages III-IV (HR=1.98 [0.9-4.33]); P=0.082. Three-year OS for stages I-II was 68% v 55% for stages III-IV (HR=1.26 [0.47-3.41]); P=0.648. Three-year PFS for chemotherapy with or without RT was 35% v 9% for RT alone (HR=1.74 [0.79-3.85]); P=0.164. Three-year OS for chemotherapy with or without RT was 66% v 34% for RT alone (HR=2.02 [0.77-5.33]); P=0.146., Conclusions: Our study corroborates GOG 150 results, and shows that paclitaxel-carboplatin appears to be an efficacious adjuvant chemotherapy regimen for completely resected uterine carcinosarcoma. The role of adjuvant RT in addition to chemotherapy warrants further investigation.