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Disease progression is a major problem in ovarian cancer. There are very few treatment options for patients with platinum‐resistant ovarian cancer (PROC), and therefore, these patients have a particularly poor prognosis. The aim of the present study was to identify markers for monitoring the response of 123 PROC patients enrolled in the Phase I/II GANNET53 clinical trial, which evaluated the efficacy of Ganetespib in combination with standard chemotherapy versus standard chemotherapy alone. In total, 474 blood samples were collected, comprising baseline samples taken before the first administration of the study drugs and serial samples taken during treatment until further disease progression (PD). After microfluidic enrichment, 27 gene transcripts were analyzed using quantitative polymerase chain reaction and their utility for disease monitoring was evaluated. At baseline, ERCC1 was associated with an increased risk of PD (hazard ratio [HR] 1.75, 95% confidence interval [CI]: 1.20–2.55; p = 0.005), while baseline CDH1 and ESR1 may have a risk‐reducing effect (CDH1 HR 0.66, 95% CI: 0.46–0.96; p = 0.024; ESR1 HR 0.58, 95% CI: 0.39–0.86; p = 0.002). ERCC1 was observed significantly more often (72.7% vs. 53.9%; p = 0.032) and ESR1 significantly less frequently (59.1% vs. 78.3%; p = 0.018) in blood samples taken at radiologically confirmed PD than at controlled disease. At any time during treatment, ERCC1‐presence and ESR1‐absence were associated with short PFS and with higher odds of PD within 6 months (odds ratio 12.77, 95% CI: 4.08–39.97; p < 0.001). Our study demonstrates the clinical relevance of ESR1 and ERCC1 and may encourage the analysis of liquid biopsy samples for the management of PROC patients. [ABSTRACT FROM AUTHOR]

Background: Carboplatin and paclitaxel (CP) have been the standard of care for advanced/recurrent endometrial cancer (EC) for many years. However, this chemotherapy combination shows limited efficacy and recurrences often occur in less than 12 months. ABTL0812 is a novel drug that selectively kill cancer cells by cytotoxic autophagy and has shown anticancer efficacy in preclinical models of EC in combination with CP. Methods: ENDOLUNG was an open-label, phase 1/2 clinical trial designed to determine the safety and efficacy of Ibrilatazar (ABTL0812) with CP in patients with advanced/recurrent EC and non-irradiable stage III and IV squamous non-small cell lung cancer (sq-NSCLC). The phase 1 part consisted of a 3 + 3 de-escalation design followed by an expansion cohort with 12 patients. The primary endpoint was safety. ABTL0812 starting dose was 1300 mg tid combined with carboplatin at area under the curve (AUC) 5 and paclitaxel at 175 mg/m2 both administered every 21 days for up to 8 cycles. The phase 2 part included a total of 51 patients. The primary endpoint was overall response rate (ORR) and the secondary endpoints included duration of response (DOR), progression-free survival (PFS) and overall survival (OS). Results: During the phase 1 only one dose limiting toxicity (DLT), a grade 4 neutropenia, was observed in 1 out of 6 patients, thus no de-escalation was applied. One additional DLT, a grade 3 febrile neutropenia, was observed in the expansion cohort, thus the recommended phase 2 dose (RP2D) for ABTL0812 was established at 1300 mg tid. Most frequent hematological adverse events (AE) of the combination were neutropenia (52.9%), anemia (37.3%) and thrombocytopenia (19.6%). Nausea (66.7%), asthenia (66.7%), diarrhea (54.9%) and vomiting (54.9%) were the most frequent non-hematological adverse events (AEs). The combination of ABTL0812 plus CP showed an ORR of 65.8% (13.2% complete response and 52.6% partial response) with a median DOR of 7.4 months (95% CI: 6.3–10.8 months). Median PFS was 9.8 months (95% CI: 6.6–10.6) and median OS 23.6 months (95% CI 6.4-ND). Pharmacokinetic parameters were compatible with target engagement observed in preclinical studies, and blood pharmacodynamic biomarkers indicated sustained target regulation during, at least, 28 days after starting the treatment. Conclusions: This study suggests that the combination of ABTL0812 with CP is safe and feasible with an encouraging activity in patients with advanced/recurrent EC. Our data warrant further confirmation in prospective randomized trials. Trial registration: EU Clinical Trial Register, EudraCT number 2016-001352-21 and National Clinical Trials Number, NCT03366480. Registration on 19 September 2016. Highlights: ABTL0812 is a novel drug in clinical development that kills tumor cells by cytotoxic autophagy. The recommended phase 1/2 dose of ABTL0812 in combination with paclitaxel/carboplatin is 1300 mg three times a day (tid) by the oral route. The combination of ABTL0812 plus carboplatin and paclitaxel (CP) in patients with advanced/recurrent EC suggests an improved benefit-to-risk ratio vs. CP alone and warrants further clinical evaluation. [ABSTRACT FROM AUTHOR]

HE4 and CA-125 are used for epithelial ovarian cancer (EOC) screening, diagnosis, and follow-up. Our objective was to study HE4 and CA-125 kinetics in patients treated for recurrent EOC. Serum samples were prospectively collected before the first chemotherapy cycle and every 3 months until disease progression. Data from 89/101 patients could be analyzed. At baseline, the median CA-125 and HE4 concentrations were 210 IU/L (7-10,310) and 184 pM (31-4,836). Among the 12 patients (13%) with normal CA-125 (<35 IU/L) concentration, eight had HE4 concentration ≥75 pM, and among the 16 patients with normal HE4 concentration (18%), 12 had increased CA-125 concentration. The median nadir concentrations were 31 IU/L (3-8,744) for CA-125 and 75 pM (20-4,836) for HE4. The median times to nadir were 14 (0-130) weeks for CA- 125 and 12 (0-52) weeks for HE4. In multivariate analysis, CA-125 and HE4 nadir concentrations (<35 IU/L, HR 0.35, 95% CI: 0.17-0.72 and<75 pM, HR 0.40, 95% CI: 0.20-0.79) and time to CA-125 and HE4 nadir (>14 weeks, HR 0.37, 95% CI: 0.20-0.70 and >12 weeks, HR 0.43, 95% CI: 0.23-0.83) were prognostic factors of progression-free survival. More investigations on HE4 kinetics could help to better monitor patients with CA-125 concentration within normal values. [ABSTRACT FROM AUTHOR]

Aims: Struma ovarii (SO) are rare, accounting for 0.3–1% of ovarian tumours, and include benign and malignant lesions. In most cases, histology is not predictive of clinical outcome and prognosis. The prognosis of histologically malignant thyroid‐type carcinomas can indeed be excellent, while SO, composed of normal thyroid tissue, can recur and are designated highly differentiated follicular carcinoma of the ovary. Clearer diagnostic criteria are therefore required. Methods and results: We retrospectively studied 31 SO using DNA and RNA sequencing with pan‐cancer gene panels, including eight biologically malignant SO (BMSO) defined based on ovarian serosal or extra‐ovarian dissemination at presentation or during follow‐up, 10 stage IA histologically malignant SO (HMSO) with thyroid‐type carcinoma morphology and 13 biologically and histologically benign SO (BSO), with none of the above‐mentioned characteristics. Molecular alterations were observed in 87.5% of BMSO, 70% of HMSO and 7.7% of BSO (P < 0.001). All patients with a peritoneal dissemination at presentation or during follow‐up had at least one gene alteration. BRAF mutations (44.5%) were only observed in malignant forms (HMSO and BMSO) and TERT promoter alterations (25%) only in cases of BMSO. The BRAF p.G469A mutation, which is extremely rare in thyroid carcinomas, was the molecular alteration most frequently associated with malignant SO (28.5%). Conclusion: Our results highlight the clinical utility of molecular sequencing in SO, based on this limited number of cases. However, as malignant SO evolve slowly, more extensive molecular studies in SO with more than 10 years' follow‐up are required to draw any conclusions on the prognostic value of the associated gene alterations. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "ENDOLUNG trial. A phase 1/2 study of the Akt/mTOR inhibitor and autophagy inducer Ibrilatazar (ABTL0812) in combination with paclitaxel/carboplatin in patients with advanced/recurrent endometrial cancer" published in BMC Cancer. The authors reported that the equal contribution statement was missing in the original submission, and they have provided the correct equal contribution statement. The correction does not make any claims about jurisdictional or institutional affiliations. The article was authored by Alexandra Leary, Purificación Estévez-García, Renaud Sabatier, Isabelle Ray-Coquard, Margarita Romeo, Pilar Barretina-Ginesta, Marta Gil-Martin, Elena Garralda, Joaquim Bosch-Barrera, Teresa Morán, Paloma Martin-Martorell, Ernest Nadal, Pere Gascón, Jordi Rodon, Jose M Lizcano, Pau Muñoz-Guardiola, Gemma Fierro-Durán, Oriol Pedrós-Gámez, Héctor Pérez-Montoyo, Marc Yeste-Velasco, Marc Cortal, Antonio Pérez-Campos, Jose Alfon, Carles Domenech, Alejandro Pérez-Fidalgo, and Ana Oaknin. [Extracted from the article]

Objective: The standard treatment for advanced endometrial cancer (EC) includes platinum-based combination chemotherapy (CT), regardless of the histology, molecular status and the patient's profile. However, EC patients are a particularly frail group of patients, often with co-morbidities. Tolerance of CT can be difficult and induce long-term toxicities. In advanced EC disease, anti-PD1 immunotherapy has shown impressive results amongst mismatch repair deficient (MMRd)/high microsatellite instability (MSI-H) tumors. However, the benefit of adding CT to anti-PD1 is still an opened question. The aim of DOMENICA is to address the question if PD-1 alone has superior efficacy to CT, so that therapy in 1L advanced/recurrent MMRd/MSI-H EC could be de-escalated to avoid CT related toxicities. Methods: DOMENICA is an academic international randomized open-label, phase III trial evaluating the efficacy and safety of dostarlimab versus carboplatin-paclitaxel in patients with MMR deficient (MMRd/MSI-H) relapse or advanced / metastatic EC. Inclusion criteria for the study comprised patients with histologically confirmed EC exhibiting recurrent or advanced disease, including primary stage IIIA to C2 or Stage IV disease, or experiencing their first recurrence of EC without curative treatment, provided they had evaluable disease according to RECIST 1.1 criteria. Additionally, patients with MMRd/MSI-H tumors, determined by institutional MMR immunohistochemistry testing, and those with a performance status (ECOG) of 0-1 were eligible. The primary endpoint is progression-free survival according to RECIST 1.1, assessed by the BICR (Blinded Independent Central Review). Secondary endpoints include overall survival as key secondary endpoint, progression-free survival 2, patients reported outcome, best objective response rate, disease control rate, duration of response rate, safety and tolerability, time to first or second subsequent treatment (TFST, TSST), pharmacokinetics and immunogenicity of dostarlimab. Exploratory objectives include predictive biomarkers, efficacy according to geriatric status. The Study is ongoing in France (GINECO), Spain (GEICO), Italy (MaNGO, MITO), Canada (PMC), Singapore (GCIG), South Korea (KGOG), Japan (GOTIC), Turkey (TRSGO), and UK (NRCI). [ABSTRACT FROM AUTHOR]

The Gynecologic Cancer InterGroup (GCIG) Endometrial Cancer Consensus Conference on Clinical Research (ECCC) was held in Incheon, South Korea, Nov 2-3, 2023. The aims were to develop consensus statements for future trials in endometrial cancer to achieve harmonisation on design elements, select important questions, and identify unmet needs. All 33 GCIG member groups participated in the development, refinement, and finalisation of 18 statements within four topic groups, addressing adjuvant treatment in high-risk disease; treatment for metastatic and recurrent disease; trial designs for rare endometrial cancer subgroups and special circumstances; and specific methodology and adaptation for trials in low-resource settings. In addition, eight areas of unmet need were identified. This was the first GCIG Consensus Conference to include patient advocates and an expert on inclusion, diversity, equity, and access to take part in all aspects of the process and output. Four early-career investigators were also selected for participation, ensuring that they represented different GCIG member groups and regions. Unanimous consensus was obtained for 16 of the 18 statements, with 97% concordance for the remaining two. Using the described methodology from previous Ovarian Cancer Consensus Conferences, this conference did not require even one minority statement. The high acceptance rate following active involvement in the preparation, discussion, and refinement of the statements by all representatives confirmed the consensus progress within a global academic setting, and the expectation that the ECCC will lead to greater harmonisation, actualisation, inclusion, and resolution of unmet needs in clinical research for individuals living with and beyond endometrial cancer worldwide., Competing Interests: Declaration of interests All authors report that the KGOG paid for their 2-night hotel stay and basic meals during the 2 days of the ECCC on Clinical Research meeting. CLC reports a research grant paid to her institution from Varian; payment to her institution for participation on a data safety monitoring board from Merck; and unpaid roles as chair of GCIG Endometrial Committee and member of Guidelines Committees for Endometrial cancer of the European Society of Gynaecologic Oncology (ESGO) and the European Society of Radiotherapy and Oncology. GE reports personal consulting fees from MSD, personal fees from Eisai, and support for attending a meeting or travel from MSD. LE reports personal consulting fees AstraZeneca, GSK, and MSD; personal fees from AstraZeneca and GSK, and support for attending a meeting or travel from AstraZeneca and GSK. RAN reports research grants paid to his institution from Elekta, Varian, and Accuray; and payment to his institution for presentations from Elekta and MSD. DL reports research grants both personal and paid to her institution from AstraZeneca, Clovis Oncology, Genmab, GSK, Immunogen, MSD, Novartis, Pharmamar, and Seagen; personal grants from Corcept, Oncoinvest, and Sutro; and grants to her institution from Incyte and Roche; consulting fees from AstraZeneca, Clovis Oncology, Corcept, Genmab, GSK, Immunogen, MSD, Novartis, Oncoinvest, Pharmamar, Seagen, and Sutro; payment for presentations from Clovis Oncology, Corcept, Genmab, GSK, Immunogen, MSD, Novartis, Oncoinvest, Pharmamar, Seagen, and Sutro; support for attending a meeting or travel from AstraZeneca, Clovis Oncology, MSD and GSK; and payments for participation on a data safety monitoring board from AstraZeneca, Clovis Oncology, Corcept, Genmab, GSK, Immunogen, MSD, Novartis, Oncoinvest, Pharmamar, Seagen, and Sutro. AO reports research grants paid to his institution from AstraZeneca; consulting fees from Bristol Myers Squibb, uncompensated participation on data and safety monitoring boards of studies funded by AstraZeneca and GlaxoSmithKline; and unpaid roles as principal investigator on investigator-initiated trials and on steering committees of trials funded by AstraZeneca and GlaxoSmithKline. BP reports research grants from Tesaro/GSK, Merck, AstraZeneca, Karyopharm Therapeutics, Sutro, Incyte, Clovis Oncology, Roche/Genentech, Mersana, Celsion/Immunon, Imab, Takeda, Toray, VBL Therapeutics, InxMed, Agenus, Seagen, NRG Oncology, Duality Bio, Xencor, Onconova, Celgene, Sutro Biopharma, Novocure, Immunogen, Eisai, Acrivon, and Alkermes; consulting fees from Tesaro/GSK, AstraZeneca, Merck, Immunogen, Gynecologic Oncology Group (GOG) Foundation, SeaGen, Lily, Eisai, Signatera, Celsion, Butro Biopharma, Imvax, Incyte, InxMed, Onconova Therapeutics, R Pharm, Regeneron, and Duality Bio; payment for presentations from Bioascend, PERS, Vanium, Curio, OncLive, Yale University and PeerView; support for attending a meeting or travel from GOG Partners, payment for participation on a data safety monitoring board or advisory board from Sutro, AstraZeneca, GOG Foundation, Celsion/Immunon, Toray, InxMed, Imvax, Imab, Tesaro/GSK, Merck, Mersana, Nuvation, and BioNtech; and unpaid leadership roles in boards, societies and committees: Society of Gynecologic Oncology (SGO) Clinical Practice Committee Chair, SGO Board of Directors, SGO COVID-19 Taskforce co-chair, GOG Partners, and New York Obstetrical Society Second VP. BH reports textbook royalties from Elsevier; consulting fees from Tempus; honoraria for lectures from Leica and Projects in Knowledge; and unpaid leadership roles on the International Society of Gynecological Pathologists Board of Directors (as member at large) and on the Endometrial Cancer MSI Committee of the College of American Pathologists. IR-C reports research grants from AstraZeneca, Clovis, GSK, Mersana, BMS, and MSD; payment for presentations from AstraZeneca, Clovis, GSK, Mersana, BMS, MSD, Roche, Pharmamar, Seagen, Eisai, and Novartis; support for attending a meeting or travel from Roche, GSK, AstraZeneca, Pharmamar, and MSD; and payment for participation on a data safety monitoring board or advisory board from Clovis, Deciphera, Adaptimmue, Sutro, and Immunogen. DG reports support for attending meetings or travel from IGCS Board of Directors; payment for participation on a data and safety monitoring board from Merck, and a leadership role in NRG Oncology. AM reports payment for participation as independent statistician on data safety monitoring boards from ONY Biotech, Regeneron, and Genentech/Roche. NC reports payments or honoraria for presentations from GSK, Seagen, Akesobio, AstraZeneca, eTheRNA immunotherapies NV, Kartos, MSD, Mersana, ImmunoGen, Eisai, Seattle Genetics, TouchIME, and Medscape Oncology; support for attending a meeting or travel from Roche, Genmab, and Amgen; payment for participation on a data safety monitoring board or advisory board from GSK, Mersana, Seagen, ImmunoGen, Akesobio, Eisai, AstraZeneca, Mersana, Seattle Genetics, eTheRNA immunotherapies NV, and Kartos; and leadership roles as President of ESGO and Chair of European Network for Gynaecological Oncological Trial groups Early Drug Development Network. MAP reports grants paid to his institution from GSK; payment for participation on a data and safety monitoring board from GSK, AstraZeneca, Eisai, Merck, Immunogen, Clovis Oncology, Jazz Pharma, and SeaGen; and payment to his institution for a leadership role on a board or committee from NRG Oncology. MAB reports payment to his institution for participation on a data and safety monitoring board from Immunogen; and employment as physician at The Permanente Medical Group. J-WK, EA, SIK, J-YP, LM, PBO, AB, DM, VG, TB, CG, TM, HW, XM-G, WS, and GS declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Ovarian carcinoma remains the most lethal gynaecologic malignancy. Half of all high-grade serous ovarian cancers (HGSOCs) have a homologous recombination deficiency (HRD) with regard to the repair of double-strand DNA breaks and are candidate to receive maintenance treatment with PARP inhibitors. While a wealth of literature exists regarding the therapeutic guidance of patients from a medical standpoint, the influence of the HRD status on the surgical outlook has been comparatively limited. In this review, the clinical and biological features of advanced ovarian cancers with BRCA1/2 mutation and/or HRD status are considered with particular reference to their impact on the surgical management and on the medico-surgical sequence. The modification of the surgical indications according to the results of molecular testing in first-line and recurrent settings are discussed., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Importance: Cervical cancer is a common and lethal cancer worldwide. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the human transforming growth factor β receptor II (or transforming growth factor β trap) fused via a flexible linker to the C-terminus of each heavy chain of an immunoglobulin G1 antibody blocking programmed cell death 1 ligand 1., Objective: To evaluate the safety and response rates of bintrafusp alfa in patients with recurrent or metastatic cervical cancer., Design, Setting, and Participants: This phase 2 nonrandomized controlled trial evaluated bintrafusp alfa monotherapy in patients with recurrent or metastatic cervical cancer with disease progression during or after platinum-based chemotherapy. Data were collected from March 2020 to February 2022., Intervention: Patients received bintrafusp alfa, 1200 mg, intravenously once every 2 weeks., Main Outcomes and Measures: The primary end point was confirmed objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 by an independent review committee., Results: At data cutoff, 146 of 203 screened patients received 1 or more doses of bintrafusp alfa; of these, the median (range) age was 53 (24-79) years. The study met its primary end point of a 95% CI above the objective response rate benchmark of 15%, with a confirmed objective response rate of 21.9% (95% CI, 15.5-29.5) per the independent review committee. Of these patients, 19 (59.4%) had a durable response of 6 months or more. At data cutoff, responses were ongoing in 13 of 32 responders (40.6%). The most common treatment-related adverse events were anemia (25 [17.1%]), rash (21 [14.4%]), hypothyroidism (15 [10.3%]), and pruritus (15 [10.3%]). Any-cause adverse events of special interest included anemia (82[56.2%]), bleeding events (81 [55.5%]), and immune-related adverse events (49 [33.6%])., Conclusions and Relevance: This phase 2 nonrandomized controlled trial of bintrafusp alfa met its primary end point, which may support the potential of a bispecific therapy targeting transforming growth factor β and programmed cell death 1 ligand 1 in patients with recurrent or metastatic cervical cancer., Trial Registration: ClinicalTrials.gov Identifier: NCT04246489.

This open-label, non-comparative, 2:1 randomized, phase II trial (NCT03275506) in women with stage IIIC/IV high-grade serous carcinoma (HGSC) for whom upfront complete resection was unachievable assessed whether adding pembrolizumab (200 mg every 3 weeks) to standard-of-care carboplatin plus paclitaxel yielded a complete resection rate (CRR) of at least 50%. Postoperatively patients continued assigned treatment for a maximum of 2 years. Postoperative bevacizumab was optional. The primary endpoint was independently assessed CRR at interval debulking surgery. Secondary endpoints were Completeness of Cytoreduction Index (CCI) and peritoneal cancer index (PCI) scores, objective and best response rates, progression-free survival, overall survival, safety, postoperative morbidity, and pathological complete response. The CRR in 61 pembrolizumab-treated patients was 74% (one-sided 95% CI = 63%), exceeding the prespecified ≥50% threshold and meeting the primary objective. The CRR without pembrolizumab was 70% (one-sided 95% CI = 54%). In the remaining patients CCI scores were ≥3 in 27% of the standard-of-care group and 18% of the investigational group and CC1 in 3% of the investigational group. PCI score decreased by a mean of 9.6 in the standard-of-care group and 10.2 in the investigational group. Objective response rates were 60% and 72%, respectively, and best overall response rates were 83% and 90%, respectively. Progression-free survival was similar with the two regimens (median 20.8 versus 19.4 months in the standard-of-care versus investigational arms, respectively) but overall survival favored pembrolizumab-containing therapy (median 35.3 versus 49.8 months, respectively). The most common grade ≥3 adverse events with pembrolizumab-containing therapy were anemia during neoadjuvant therapy and infection/fever postoperatively. Pembrolizumab was discontinued prematurely because of adverse events in 23% of pembrolizumab-treated patients. Combining pembrolizumab with neoadjuvant chemotherapy is feasible for HGSC considered not completely resectable; observed activity in some subgroups justifies further evaluation to improve understanding of the role of immunotherapy in HGSC., (© 2024. The Author(s).)

PD-1/PD-L1 blockade has so far shown limited survival benefit for high-grade ovarian carcinomas. By using paired samples from the NeoPembrOv randomized phase II trial (NCT03275506), for which primary outcomes are published, and by combining RNA-seq and multiplexed immunofluorescence staining, we explore the impact of NeoAdjuvant ChemoTherapy (NACT) ± Pembrolizumab (P) on the tumor environment, and identify parameters that correlated with response to immunotherapy as a pre-planned exploratory analysis. Indeed, i) combination therapy results in a significant increase in intraepithelial CD8 + PD-1 + T cells, ii) combining endothelial and monocyte gene signatures with the CD8B/FOXP3 expression ratio is predictive of response to NACT + P with an area under the curve of 0.93 (95% CI 0.85-1.00) and iii) high CD8B/FOXP3 and high CD8B/ENTPD1 ratios are significantly associated with positive response to NACT + P, while KDR and VEGFR2 expression are associated with resistance. These results indicate that targeting regulatory T cells and endothelial cells, especially VEGFR2 + endothelial cells, could overcome immune resistance of ovarian cancers., (© 2024. The Author(s).)

Objective: In the PAOLA-1/ENGOT-ov25 trial (NCT02477644), adding maintenance olaparib to bevacizumab provided a substantial progression-free survival benefit in patients with newly diagnosed advanced ovarian cancer and homologous recombination deficiency (HRD)-positive tumors, irrespective of clinical risk. Subsequently, a clinically meaningful improvement in overall survival was reported with olaparib plus bevacizumab in the HRD-positive subgroup. We report updated progression-free survival and overall survival by clinical risk and HRD status., Methods: Patients in clinical response after first-line platinum-based chemotherapy plus bevacizumab received maintenance olaparib (up to 24 months) plus bevacizumab (up to 15 months in total) or placebo plus bevacizumab. This post hoc analysis evaluated 5-year progression-free survival and mature overall survival in patients classified by clinical risk and HRD status., Results: Of 806 randomized patients, 74% were higher-risk and 26% were lower-risk. In higher-risk HRD-positive patients, the hazard ratio (HR) for progression-free survival was 0.46 (95% confidence interval (95% CI) 0.34 to 0.61), with 5-year progression-free survival of 35% with olaparib plus bevacizumab versus 15% with bevacizumab alone; and the HR for overall survival was 0.70 (95% CI 0.50 to 1.00), with 5-year overall survival of 55% versus 42%, respectively. In lower-risk HRD-positive patients, the HR for progression-free survival was 0.26 (95% CI 0.15 to 0.45), with 5-year progression-free survival of 72% with olaparib plus bevacizumab versus 28% with bevacizumab alone; and the HR for overall survival was 0.31 (95% CI 0.14 to 0.66), with 5-year overall survival of 88% versus 61%, respectively. No benefit was seen in HRD-negative patients regardless of clinical risk., Conclusion: This post hoc analysis indicates that in patients with newly diagnosed advanced HRD-positive ovarian cancer, maintenance olaparib plus bevacizumab should not be limited to those considered at higher risk of disease progression. Five-year progression-free survival rates support long-term remission and suggest an increased potential for cure with particular benefit suggested in lower-risk HRD-positive patients., Competing Interests: Competing interests: Domenica Lorusso reports consultancy fees (personal) from Amgen, AstraZeneca, Clovis Oncology, Genmab, GSK, Immunogen, MSD, PharmaMar, and Seagen; membership on an advisory board (personal) for AstraZeneca, Clovis Oncology, Corcept, Genmab, GSK, Immunogen, Merck Serono, MSD, Oncoinvest, PharmaMar, Seagen, and Sutro; and research funding (institutional) from AstraZeneca, Clovis Oncology, Genmab, GSK, Immunogen, Incyte, MSD, Novartis, PharmaMar, Roche, and Seagen; and travel support from Roche, PharmaMar, AstraZeneca, Clovis Oncology, and GSK. Marie-Ange Mouret-Reynier reports board membership (personal and institution) for Pfizer, Lilly, Novartis, MSD, and AstraZeneca; and research funding (personal and institution) from Pfizer, Lilly, Novartis, MSD, and AstraZeneca. Philipp Harter reports honoraria from Amgen, AstraZeneca, GSK, Roche, Sotio, Stryker, Zai Lab, MSD, Clovis, Eisai, Mersana, and Exscientia; membership on an advisory board for AstraZeneca, Roche, GSK, Clovis, Immunogen, MSD, Miltenyi, Novartis, and Eisai; and research funding (institutional) from AstraZeneca, Roche, GSK, Genmab, Immunogen, Seagen, Clovis, and Novartis. Claire Cropet reports no conflicts of interest. Cristina Caballero reports no conflicts of interest. Pia Wolfrum-Ristau reports no conflicts of interest.Toyomi Satoh reports no conflicts of interest. Ignace Vergote reports consulting fees (personal) from Agenus, Akesobio, AstraZeneca, BMS, Deciphera Pharmaceuticals, Eisai, Elevar Therapeutics, Exelixis, Roche, Genmab, GSK, Immunogen, Jazz Pharmaceuticals, Karyopharm, Mersana, Molecular Partners, MSD, Novocure, Novartis, Oncoinvent, OncXerna, Regeneron, Sanofi, Seagen, Sotio, Verastem Oncology, and Zentalis; contracted research (via KULeuven; institution) for Oncoinvent AS; corporate sponsored research (institution) from Amgen and Roche; and travel support (personal) from Karyopharm, Genmab, and Novocure.Gabriella Parma reports no conflicts of interest. Trine Jakobi Nøttrup reports no conflicts of interest. Coriolan Lebreton reports honoraria (personal) from Eisai, Clovis Oncology, MSD, and GSK. Peter A Fasching reports membership on an advisory board (personal) for Agendia, AstraZeneca, Daiichi-Sankyo, Eisai, Hexal, Lilly, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi Aventis, and Seagen; invited speaker fees (personal) from AstraZeneca, Daiichi-Sankyo, Eisai, Gilead, Lilly, MSD, Novartis, and Seagen; and medical writing support (personal) from Roche. Carmela Pisano reports membership on an advisory board (personal) for AstraZeneca, MSD and GSK; and honoraria (personal) from Clovis Oncology. Luis Manso reports no conflicts of interest. Hugues Bourgeois reports no conflicts of interest. Ingo Runnebaum reports no conflicts of interest. Claudio Zamagni reports reports grants or contract to self from Amgen, Celgene, Daiichi, Eisai, Eli Lilly, GSK, MSD, and PharmaMar; grants or contract to self and institution from AstraZeneca, Instituto Gentili, Novartis, Pfizer, Pierre Fabre, Roche, Seagen, Tesaro, and Teva; support for attending meetings and/or travel from Celgene, Instituto Gentili, Novartis, Pfizer, PharmaMar, Pierre Fabre, Roche, and Tesaro; participation on a data safety monitoring board or advisory board for Amgen, AstraZeneca, Celgene, Daiichi, Eisai, Eli Lilly, GSK, MSD, Novartis, Pfizer, PharmaMar, QuintilesIMS, Roche, and Tesaro; and other financial or non-interests for Amgen, AstraZeneca, Daiichi, GSK, MSD, Novartis, Pfizer, PharmaMar, QuintilesIMS, Roche, and Tesaro. Anne-Claire Hardy-Bessard reports membership on an advisory board (personal) for MSD, AstraZeneca, GSK, Pfizer, and Novartis. Andreas Schnelzer reports no conflicts of interest. Michel Fabbro reports honoraria from GSK. Barbara Schmalfeldt reports honoraria from Roche, AstraZeneca, Tesaro, Clovis, GSK, and MSD; consultancy or advisory roles from Roche, AstraZeneca, Tesaro, Clovis, GSK, and MSD; membership of a speaker’s bureau for Roche, AstraZeneca, Tesaro, Clovis, GSK, and MSD; research funding from Roche, AstraZeneca, Tesaro, Clovis, GSK, and MSD; and funding for travel or accommodation expenses from Roche, AstraZeneca, and Tesaro. Dominique Berton reports no conflicts of interest. Antje Belau reports honoraria from Roche, AstraZeneca, Clovis, MSD, Daiichi Sankyo Company, Lilly, and Seagen; advisory roles for Pfizer, Roche, AstraZeneca, MSD, Lilly, Daiichi Sankyo Company, and Seagen; and funding for travel or accommodation expenses from Roche, AstraZeneca, and Daiichi Sankyo Company. Jean-Pierre Lotz reports no conflicts of interest. Martina Gropp-Meier reports no conflicts of interest. Laurence Gladieff reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Clovis, Eisai, GSK, and MSD; and participation on an advisory board for AstraZeneca, GSK, and MSD. Hans-Joachim Lück reports participation on advisory boards for AstraZeneca, GSK, Seagen, Gilead, Novartis, and Lilly and speaker roles for AstraZeneca, Lilly, Gilead, Pfizer, and Novartis. Sophie Abadie-Lacourtoisie reports no conflicts of interest. Eric Pujade-Lauraine reports membership on an advisory board (personal) for Roche, GSK, and AstraZeneca; Independent Data Monitoring Committee board membership (personal) for Agenus and Incyte; and employment (personal) at ARCAGY Research. Isabelle Ray-Coquard reports honoraria (personal) from Abbvie, Agenus, Advaxis, BMS, PharmaMar, Genmab, Pfizer, AstraZeneca, Roche, GSK, MSD, Deciphera, Mersena, Merck Sereno, Novartis, Amgen, Tesaro, and Clovis Oncology; honoraria (institution) from GSK, MSD, Roche, and BMS; advisory/consulting fees from Abbvie, Agenus, Advaxis, BMS, PharmaMar, Genmab, Pfizer, AstraZeneca, Roche/Genentech, GSK, MSD, Deciphera, Mersena, Merck Sereno, Novartis, Amgen, Tesaro, and Clovis Oncology; research grant/funding (personal) from MSD, Roche, and BMS; research grant/funding (institution) from MSD, Roche, BMS, Novartis, AstraZeneca, and Merck Sereno; and travel support from Roche, AstraZeneca, and GSK., (© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

The landscape of uterine sarcomas is becoming more complex with the description of new entities associated with recurrent driver molecular alterations. Uterine sarcomas, in analogy with soft tissue sarcomas, are distinguished into complex genomic and simple genomic sarcomas. Leiomyosarcomas and undifferentiated uterine sarcomas belong to complex genomic sarcomas group. Low-grade and high-grade endometrial stromal sarcomas, other rare tumors associated with fusion transcripts (such as NTRK, PDGFB, ALK, RET ROS1) and SMARCA4-deficient uterine sarcoma are considered simple genomic sarcomas. The most common uterine sarcoma are first leiomyosarcoma and secondly endometrial stromal sarcomas. Three different histological subtypes of leiomyosarcoma (fusiform, myxoid, epithelioid) are identified, myxoid and epithelioid leiomyosarcoma being more aggressive than fusiform leiomyosarcoma. The distinction between low-grade and high-grade endometrial stromal sarcoma is primarily morphological and immunohistochemical and the detection of fusion transcripts can help the diagnosis. Uterine PEComa is a rare tumor, which is distinguished into borderline and malignant, according to a risk assessment algorithm. Embryonal rhabdomyosarcoma of the uterine cervix is more common in children but can also occur in adult women. Embryonal rhabdomyosarcoma of the uterine cervix is almost always DICER1 mutated, unlike that of the vagina which is wild-type DICER1, and adenosarcoma which can be DICER1 mutated but with less frequency. Among the emerging entities, sarcomas associated with fusion transcripts involving the NTRK, ALK, PDGFB genes benefit from targeted therapy. The integration of molecular data with histology and clinical data allows better identification of uterine sarcomas in order to better treat them., (Copyright © 2023 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)