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Objectives: Newly diagnosed advanced ovarian cancer patients (pts) are at high risk of relapse and 5-year survival is 30–50%. Delay of recurrence, prolonged survival and, for some pts, increased chance of cure are goals of treatment in this setting. In SOLO1 (NCT01844986; GOG-3004) pts with advanced ovarian cancer and a BRCA1 and/or BRCA2 mutation (BRCAm) who were in response after first-line platinum-based chemotherapy derived significant progression-free survival (PFS) benefit from maintenance olaparib vs placebo (median 41 months follow-up; median not reached vs 13.8 months; hazard ratio 0.30; P Methods: Pts received maintenance olaparib (tablets; 300 mg bid) or placebo for up to 2 years or until progression. PFS and recurrence-free survival (RFS) were investigator-assessed by modified RECIST v1.1. An exploratory subgroup analysis of PFS in higher-risk (stage IV disease, stage III disease with residual disease following primary debulking surgery, inoperable stage III disease, or stage III disease and had undergone interval surgery) and lower-risk (stage III disease without residual disease following primary debulking surgery) pts was carried out. For pts in complete response at baseline, RFS was defined post hoc as time from randomization to disease recurrence (new lesions by imaging) or death. Download : Download high-res image (174KB) Download : Download full-size image Results: A total of 260 pts were randomized to olaparib; 131 to placebo (median treatment duration 24.6 vs 13.9 months, respectively). After a median of 4.8 and 5.0 years of follow-up, median PFS was 56 vs 14 months in the olaparib and placebo arms, respectively (Table). In the higher-risk subgroup 42% of olaparib-arm vs 17% of placebo-arm pts were free from progression at 5 years; in the lower-risk subgroup 56% vs 25% of pts, respectively, were progression free at this time point. Among pts in complete response at baseline, risk of disease recurrence or death was reduced by 63%. The safety profile of olaparib was consistent with previous observations. No new cases of myelodysplastic syndrome or acute myeloid leukaemia were reported (previous DCO: olaparib, 3/260 [1%]; placebo, 0/130), and incidence of new primary malignancies remained balanced between arms (olaparib, 7/260 [3%]; placebo, 5/130 [4%]). Conclusions: For pts with a BRCAm and newly diagnosed advanced ovarian cancer, the benefit derived from 2 years of maintenance olaparib was sustained beyond the end of treatment, and after 5 years, almost half of pts were progression free vs 20% with placebo. This benefit was consistent across higher- and lower-risk pts. Over 50% of pts in complete response after first-line platinum-based chemotherapy remained free from relapse 5 years after randomization. A total of 5 years of follow-up is the longest for any PARP inhibitor in this setting and no new safety signals were observed.

BACKGROUND Cervical cancer (CC) remains a leading cause of gynaecological cancer-related mortality world wide and constitutes the third most common malignancy in women. The RAIDs consortium ( http://www.raids-fp7.eu/ ) conducted a prospective European study [BioRAIDs (NCT02428842)] with the objective to stratify CC patients for innovative treatments. A “metagene” of genomic markers in the PI3K pathway and epigenetic regulators had been previously associated with poor outcome [2] . METHODS To detect new, more specific, targets for treatment of patients who resist standard chemo-radiation, a high-dimensional Cox model was applied to define dominant molecular variants, copy number variations, and reverse phase protein arrays (RPPA). FINDINGS Survival analysis on 89 patients with all omics data available, suggested loss-of-function (LOF) or activating molecular alterations in nine genes to be candidate biomarkers for worse prognosis in patients treated by chemo-radiation while LOF of ATRX, MED13 as well as CASP8 were associated with better prognosis. When protein expression data by RPPA were factored in, the supposedly low molecular weight and nuclear form, of beta-catenin, phosphorylated in Ser552 (pβ-Cat552), ranked highest for good prognosis, while pβ-Cat675 was associated with worse prognosis. INTERPRETATION These findings call for molecularly targeted treatments involving p53, Wnt pathway, PI3K pathway, and epigenetic regulator genes. Pβ-Cat552 and pβ-Cat675 may be useful biomarkers to predict outcome to chemo-radiation, which targets the DNA repair axis. FUNDING European Union's Seventh Program for research, technological development and demonstration (agreement N°304,810), the Fondation ARC pour la recherche contre le cancer.

BACKGROUND: There is a lack of information as to which molecular processes, present at diagnosis, favor tumour escape from standard-of-care treatments in cervical cancer (CC). RAIDs consortium (www.raids-fp7.eu), conducted a prospectively monitored trial, [BioRAIDs (NCT02428842)] with the objectives to generate high quality samples and molecular assessments to stratify patient populations and to identify molecular patterns associated with poor outcome. METHODS: Between 2013 and 2017, RAIDs collected a prospective CC sample and clinical dataset involving 419 participant patients from 18 centers in seven EU countries. Next Generation Sequencing has so far been carried out on a total of 182 samples from 377 evaluable (48%) patients, allowing to define dominant genetic alterations. Reverse phase protein expression arrays (RPPA) was applied to group patients into clusters. Activation of key genetic pathways and protein expression signatures were tested for associations with outcome. FINDINGS: At a median follow up (FU) of 22 months, progression-free survival rates of this FIGO stage IB1-IV population, treated predominantly (87%) by chemoradiation, were65•4% [CI95%: 60•2-71.1]. Dominant oncogenic alterations were seen in PIK3CA (40%), while dominant suppressor gene alterations were seen in KMT2D (15%) and KMT2C (16%). Cumulative frequency of loss-of-function (LOF) mutations in any epigenetic modulator gene alteration was 47% and it was associated with PIK3CA gene alterations in 32%. Patients with tumours harboring alterations in both pathways had a significantly poorer PFS. A new finding was the detection of a high frequency of gains of TLR4 gene amplifications (10%), as well as amplifications, mutations, and non-frame-shift deletions of Androgen receptor (AR) gene in 7% of patients. Finally, RPPA protein expression analysis defined three expression clusters. INTERPRETATION: Our data suggests that patient population may be stratified into four different treatment strategies based on molecular markers at the outset. FUND: European Union's Seventh Program grant agreement No 304810.

Resume Introduction Expression IV est une enquete europeenne evaluant les attentes des patientes suivies pour un cancer de l’ovaire concernant les traitements d’entretien. Methode Quatre cent une patientes francaises ont repondu a un questionnaire anonyme. L’objectif etait d’evaluer les connaissances et attentes des patientes vis-a-vis des traitements d’entretien. Resultats Parmi les patientes, 62 % ont recu une information concernant le traitement d’entretien. Parmi les femmes, 37 % beneficiaient d’un traitement d’entretien. Les attentes des patientes etaient une augmentation des chances de guerison pour 73 % d’entre elles, une diminution de la taille tumorale (36 %), une amelioration de la qualite de vie (35 %) et un ralentissement de la croissance tumorale (27 %). Parmi les patientes, 64 % esperaient un gain de survie sans progression (SSP) de plus de 6 mois. Parmi les patientes, 42 % etaient pretes a prendre le traitement pendant 6 a 24 mois, 20 % jusqu’a 60 mois et 38 % jusqu’a progression. Les patientes de plus de 70 ans etaient moins bien informees (48 % vs 66 %) et avaient moins d’espoir de guerison (60 % vs 77 %) que les plus jeunes. Les patientes en rechute avaient plus d’attentes que celles en remission (diminution de la taille tumorale : 47 % vs 22 %, ralentissement de la croissance tumorale : 37 % vs 15 %, survie sans progression superieure a 6 mois : 71 % vs 53 %), etaient pretes a prendre le traitement plus longtemps (prise du traitement jusqu’a progression : 48 % vs 24 %). Conclusion Il existe un ecart entre le benefice publie des traitements d’entretien dans le cancer de l’ovaire et les esperances des patientes necessitant davantage d’informations.

Resume Introduction Les tumeurs malignes rares de l’ovaire regroupent les tumeurs borderline complexes, les tumeurs germinales, les tumeurs des cordons sexuels et les tumeurs epitheliales rares. Les indications et modalites de preservation de la fertilite, la prise en charge d’une infertilite, les possibilites de contraception et de traitement hormonal de la menopause sont des questions frequentes en pratique clinique. Un groupe d’experts du reseau national dedie aux cancers gynecologiques rares (TMRG/TMRO) associe a des experts nationaux de la fertilite, des traitements hormonaux et de la contraception se sont reunis pour proposer des recommandations nationales. Methodes Un panel de 39 experts de differentes specialites a participe a l’elaboration des recommandations, en suivant la methode DELPHI (consensus formalise d’experts). Apres revue systematique de la litterature, des recommandations ont ete redigees puis soumises a deux tours successifs de cotations. Resultats Trente-cinq recommandations ont ete retenues, precisant les indications de preservation de la fertilite, les situations contre-indiquant une stimulation ovarienne (en preservation de la fertilite ou dans la prise en charge d’une infertilite), les possibilites de contraceptions (notamment hormonales) et de traitement hormonal de la menopause pour chaque type tumoral. De facon generale, une prudence a ete retenue pour les tumeurs potentiellement hormonosensibles comme les tumeurs des cordons sexuels, les adenocarcinomes sereux et endometrioides de bas grade, ainsi que pour les tumeurs borderline avec criteres histologiques pejoratifs. Discussion Dans le contexte d’une litterature pauvre, ces recommandations etablies via consensus formalise d’experts devraient constituer une aide aux cliniciens dans la prise en charge de ces patientes.

Thyroid carcinoma on struma ovarii (TCSO) is a rare ovarian tumour, derivate from monodermic teratomas. It represents about 0.01% of overall ovarian tumours and 5 to 10% of struma ovarii. The diagnosis is histologic and retrospective after pelvic surgery; radiographic imaging being unspecific. Because of its rarity, the treatment of TCSO is not consensual and should be validated in multidisciplinary team involved in rare ovarian carcinoma. The first treatment is a surgical removal, with a laparoscopic approach. A fertility-conservative surgery is recommended for young women. If the tumour is unresectable and/or with metastatic spread, an adjuvant iodine 131 treatment might be proposed after thyroidectomy. Recurrence of TCSO should be taken care of as a thyroid carcinoma with tyrosine kinase inhibitor in case of progressive distant relapse, refractory to iodine 131 treatment. If the recurrence is localised, a complete surgery is the preferred option. There is no gold standard for the follow up.

Sustainable land management is of utmost importance in Ethiopia and relies on Soil and Water Conservation (SWC) measures collectively implemented by smallholders through participatory processes. This paper contributes systematic evidence on how SWC strategies are implemented and how participation is operationalized. Drawing upon inductive, qualitative research, we explore the design, implementation and evaluation of SWC activities, as they relate to Ostrom’s Institutional Analysis and Development (IAD) framework, in order to determine how the activities can be made more appropriate, effective and sustainable. Findings show that on all levels of Ostrom’s framework, there are shortcomings in the SWC institutions, which have to be addressed with more participatory approaches, a change from top-down to bottom-up measures, and economic incentives for farmers to invest in SWC measures instead of e.g. compulsory labor, and the integration of so far neglected groups like youth, women and the landless.

Resume But La prise en charge du cancer de l’endometre est en constante evolution. La SFOG et le CNGOF se sont accordes pour remettre a jour les recommandations francaises (Institut national du cancer 2011) et pour adapter a la pratique francaise les recommandations 2015 issues de la conference de consensus europeenne reunissant les trois societes europeennes concernees (ESGO, ESTRO, ESMO). Materiel et methodes Une methodologie stricte a ete suivie, comportant la creation d’un groupe de pilotage, une revue bibliographique systematique, une elaboration de recommandations prenant en compte le niveau de preuve et une revue externe par des utilisateurs issus de toutes les disciplines et tous les modes d’exercice concernes (304 remarques par 54 relecteurs). Resultats Le traitement du cancer de l’endometre necessite un bilan preoperatoire rigoureux permettant d’emettre une prevision, imparfaite, du stade. Cette evaluation permet d’orienter le niveau de stadification chirurgicale requis. La chirurgie doit etre autant que possible etre realisee par technique minimalement invasive. L’etude anatomopathologique finale est la cle de la decision de traitement adjuvant, qui comporte de maniere variable surveillance, radiotherapie, curietherapie ou chimiotherapie. Conclusion Les algorithmes de prise en charge permettront de repondre rapidement, sur la base du niveau de connaissance actuel, aux problemes poses par le cancer de l’endometre. Ils doivent etre integres dans une discussion pluridisciplinaire a toutes les etapes du traitement.

BackgroundThere is a medical need in platinum resistant ovarian cancer patients. Median progression-free survival (PFS) is 3.4 months with chemotherapy and 6.7 months with chemotherapy-bevacizumab combination regimens.1 RECIST overall response rate (ORR) is 11.8% and 27.3%, respectively. The ORR is 15.9% for bevacizumab as a monotherapy with a median PFS of 4.4 months.2MethodsNCT03596281 An open-label phase 1b trial with a modified toxicity probability interval design to evaluate the combination of a flat dose of 400mg bevacizumab for 6 cycles and 200mg pembrolizumab until disease progression, unacceptable toxicity or completed 24 months of treatment in patients with platinum resistant ovarian cancer. The primary evaluation criteria is safety, the secondary endpoint is the efficacy.Results19 patients have been enrolled between January 2019 and February 2021 in 6 French centers. Patients‘ characteristics are reported (table 1). No dose limiting toxicities were observed. Grade 3 treatment related adverse events occurred in 3 patients (i.e. arterial thromboembolism, bowel perforation, proteinuria and sepsis). No grade 4/5 toxicities were induced. A median of 7 cycles (range 3–14) were administered. Median follow-up of patients was 4.1 months (1.8–23). The RECIST ORR was 26.3% (1 complete response and 4 partial responses) (table 2). The disease control rate was 78.9%. The time to progression was not yet reached in 6 patients. The ORR was equivalent whether patients have been pretreated or not with bevacizumab (27.3 and 25% respectively) (table 3). The ORR according to the combined positive score (CPS) for the evaluation of PD-L1 was 50.0% for CPS≥10% (n=4), 30.0% for a CPS≥1% (n=10) and 25.0% for CPSConclusionsA chemotherapy-free regimen combining pembrolizumab and bevacizumab was well tolerated and showed encouraging results in heavily pretreated platinum resistant ovarian cancer patients independent of their previous challenge with antiangiogenic agents.AcknowledgementsFunding for this research was provided by Fondation Cancer du Luxembourg and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.Trial RegistrationNCT03596281ReferencesPujade-Lauraine E, et al. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Onco Off J Am Soc Clin Oncol 32,1302–1308 (2014).Cannistra SA, et al. Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol Off J Am Soc Clin Oncol 33,5180–5186 (2007).Ethics ApprovalThis study was approved by CPP Sud Méditerranée V institution’s Ethics Board; approval number 18.020 (EudraCT number 2017-004197-34).ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

Background: Although video teleconsultations (TCs) have shown benefits for clinical follow up in oncology, its development appears very delayed in routine practice. The COVID pandemic has required French physicians to use them, mostly during the first lockdown period. This study aims to identify barriers to TCs development by assessing patient’s and physician’s satisfaction regarding this experience. Methods: Patients who took part in at least one TC during the 7 weeks of strict confinement (from March 7 to May 11, 2020) were asked via email to complete a questionnaire of close-ended questions (5 points Likert scale) with the possibility of additional comments. Their answers were anonymized and gathered via Sphinx, a secured statistical analysis software. A second questionnaire was sent to each physician who conducted these TCs. We then aimed to analyze each patient and physician characteristics and comments, according to their degree of overall satisfaction. Results: 531 patients and 35 physicians (oncologists, surgeons, anesthetists, radiotherapists) used TCs;307 patients (57.8%) and 31(88.5%) physicians completed the survey. Patient’s average age was 59. 140 (46.7%) of them lived in a rural area and 193 (64.3%) lived more than one hour away from their cancer center;66.9% of them were overall satisfied. Unsatisfied patients (12.1%) had the same characteristics as the overall population. Apart from the lack of clinical examination, the main complaints of this group of patients were about altered communication with their physician (44.4% vs 22%), troubles with technical set up (38.9% vs 13.5%) leading to 50% of consultations by phone. Average satisfaction rate among physician was 80.7%. They mainly reported altered relationship with their patient, mostly during tough announcements. Preferred indications were surveillance consultation and treatment monitoring. Conclusions: This study shows high rate of overall satisfaction, from both patients and physicians. TCs seem to provide a suitable alternative to standard in-person consultations, therefore improvements are needed to optimize this technique. Legal entity responsible for the study: Institut Bergonie. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Since 2004–2005 the cotton sector in Benin has been experiencing major problems that have caused a decline in production. To help the sector recover, the government intensified its intervention in the form of prices support. This study assesses the impacts of sharp increases in producer prices during the years 2009–2012 on cotton production and the distributional impacts on welfare. Using a partial adjustment model of supply response, we estimate that cotton supply elasticity ranges between 1.3 and 2.6, suggesting that cotton production responds strongly to price incentives. Next, we use concepts of compensating variation and net benefit ratio measures to analyse the welfare implications. We find that an increase in price from 190 FCFA per kg in 2009 to 250 FCFA per kg in 2012 led to a 9.8 percent increase in producers’ welfare. Non-parametric regressions showed that the increase in cotton prices likely benefited all households across the entire income distribution. However, the gains are larger for rich farmers in the northern regions where cotton is predominant.

Resume Malgre l’amelioration des traitements, le taux de guerison des cancers de l’ovaire n’a pas significativement change. Les rechutes restent frequentes et sont encore synonymes d’entree dans la maladie chronique. La plupart des rechutes sont platine sensibles et peuvent etre traitees avec succes par des lignes successives de chimiotherapies. La chirurgie semble bien avoir un role a jouer mais son reel impact, ses criteres de selection et le meilleur moment de sa realisation restent a etablir. En ce qui concerne les traitements medicaux, la mise a disposition de nouvelles molecules comme le bevacizumab et l’olaparib rendent la prise de decision plus complexe. En outre, des reactions de type allergique peuvent survenir, qui peuvent etre genantes surtout quand elles concernent un derive de platine. En pratique, le choix repose sur le profil et les souhaits des patientes, sur le type et le nombre de lignes anterieures ainsi que sur le statut par des genes de recombinaisons homologues BRCA.

New farming technologies such as improved fallow of herbaceous legumes have been developed over the last 20 years as alternatives to traditional yam cropping systems in areas where shifting cultivation is no more possible. One aim of this research was to analyze actual adoption by smallholders of such a technology and influencing factors in the Southern Guinea Savannah in Benin (West Africa). On the other hand, a second objective was to measure agronomic and economic performances of the innovative yam-based cropping systems in comparison with the usual ones under producers’ natural and socioeconomic circumstances in order to discuss the technology potential for large scale adoption. Smallholders with limited land access now develop as usual cropping systems a one-year fallow of Andropogonon gayanus–yam rotation or a maize–yam rotation. Innovative sedentary yam-based systems consist of an Aeschynomene histrix intercropped with maize–yam rotation or a Mucuna pruriens intercropped with maize–yam rotation. Factors potentially affecting adoption were included in a polynomial logit model. Agronomic and economic performances were assessed by the multiple regression and net present value of the 4-years double rotation. Ranking matrix was used to highlight constraints that may impede adoption. Benefits, lessons, and challenges are discussed in this article.

Backround: Patients with metastatic endometrial carcinoma have a poor prognosis and PIK3CA mutations and amplifications are common in these cancers. This study evaluated the efficacy and safety of the pure PI3K inhibitor BKM120 in advanced or recurrent endometrial carcinoma. Methods: This phase II, multicentre, single-arm, double strata (histological low grade (LG) or high grade (HG)) open-label study enrolled patients with histologically confirmed advanced or recurrent endometrial carcinoma who had received not more than one prior chemotherapy regimen. Patients received initially BKM120 100 mg tablets once daily. Primary end points were proportion of patients free of progression at 2 months (HG strata) or at 3 months (LG strata), objective response rate (ORR), and safety. Results: A total of 40 patients were enrolled, of whom 16 patients had received BKM120 at 100 mg. Because of high toxicities (cutaneous rash (54%), depressive events (47%), and anxiety (40%), the IDMC has proposed to stop recruitment at 100 mg and to continue the clinical trial with a lower dose of 60 mg per day. In addition, 24 patients (median age 67 years old) were newly enrolled (14 in the LG strata and 10 in the HG strata). Rate of nonprogression at 2 months in the HG strata was 70% and at 3 months was 60% in the LG strata. Median progression-free survival (PFS) for all patients is 4.5 months (CI 95% 2.8–6.1), and the median PFS for LG strata is 8.3 months compared with 3.8 months for the HG strata. No response was reported. At 60 mg per day, the most commonly reported treatment-related adverse events (AEs) were hyperglycaemia (58%), cognitive (31%), digestive (28%), hepatic liver functions (26%), and rash (23%). The most commonly reported treatment-related grade ⩾3 AEs were HTA (17%), hyperglycaemia (17%), and increased alanine aminotransferase (24%). Five patients (21%) stopped BKM120 for toxicity. Conclusions: The BKM120 was associated with an unfavourable safety profile and minimal antitumour activity in monotherapy in advanced or recurrent endometrial carcinoma. The clinical trial was stopped before end of recruitment for toxicity.

Introduction/Background In SOLO1 trial, maintenance therapy with olaparib considerably improved progression-free survival (PFS) among women with newly-diagnosed, advanced BRCA-mutated HGEOC. Based on the large real-life ESME ovarian cancer (OC) cohort, we aimed to describe the patient‘s characteristics and survival outcomes of a selected cohort of BRCA-mutated patients before the era of PARP inhibitors maintenance in first line. Methodology ESME OC is a national cohort including all patients (pts) with EOC managed in the 18 French Comprehensive Cancer Centres (NCT03275298). ESME Research program collected retrospective data from patient‘s medical records. BRCA1, BRCA2, or both mutated patients with de novo diagnosed advanced (FIGO stage III or IV) high-grade serous or endometrioid EOC were eligible. Primary objective was to describe patient‘s characteristics, clinical features and treatment patterns. Results Of the 4777 patients with OC treated in first line by platinum-based chemotherapy between 2011 and 2016, 266 were included. Median age was 57.0 (33–81). 187 pts (70.3%) harbored a BRCA1 mutation, and 75 (28.2%) a BRCA2 mutation. 66.9% of patients had FIGO stage III disease. Almost all patients (95.5%) underwent surgical resection, after neoadjuvant chemotherapy (48%), or primary debulking surgery (44.9%). 119 pts (44.7%) received maintenance therapy and majority with bevacizumab alone (78.9%). After a median follow-up of 51.7months, the median PFS (mPFS) was 28.6months [95 CI: 26.2–32.4]. Patients exhibited higher mPFS in case of FIGO stage III than stage IV (32.4 months and 25.4 months, respectively), or BRCA2 mutation than BRCA1 (33.3 months and 27.7 months, respectively). Although populations were non comparable, mPFS was close between patients treated with or without maintenance (28.3 and 29.5 months, respectively). Median PFS2 were 51.4 months and 50.4 months, respectively. Estimated 5-year OS for the whole population was 69.2% [95 CI: 65.3–73.0]. Conclusion This large ESME OC cohort described clinical features and real-life survival outcomes among pts with newly diagnosed advanced BRCA-mutated HGEOC treated in specialized centres. Disclosure This work was supported by UNICANCER. The ESME OC database is supported by an industrial consortium (Roche, Pfizer, AstraZeneca, MSD, Eisai and Daiichi Sankyo). Data collection, analyses and publications are totally managed by R&D UNICANCER independently of the industrial consortium. All the authors declare that there is no conflict of interest regarding the publication of this article.

Introduction/Background Surgery is the cornerstone of ovarian Granulosa Cell Tumor (GCT). Complete resection with adequate staging is the gold standard in 1st line setting. The aim of this study is to assess the impact of an appropriate surgery according to the guidelines. Methodology This is a nationwide five-year retrospective study, including 463 patients (of the 639 included patients) with a definitive diagnosis of GCT between 2011 and 2016. Medical and surgical practices were analyzed for conformity. Conformity to guidelines was defined by a conservative (unilateral salpingo-oophorectomy) or radical surgery (hysteretomy and bilateral salpingo-oophorectomy) including surgical staging (omentectomy, peritoneal biopsy and peritoneal cytology) according to the FIGO classification. Results Median age at diagnosis was 49 years old (range 10–89). The median size of tumor was 94 mm (range 5–400). Radical surgery was performed in 240 patients (51,8%), while a fertility-sparing surgery was performed in 98 cases (21,2%). A complete surgical staging was performed in only 76 cases (16,4%). 289 (62.4%) patients received an evaluation of the endometrium (hysterectomy or endometrial curettage). Surgery was fully compliant with the guidelines in 65 patients (14%), partially compliant in 213 patients (46%), non-compliant in 137 patients (29,6%) and not assessable in 48 cases (10,4%) respectively. A statistically significant improvement in the surgical management was observed among patients treated after 2012 compared to those treated before 2012. This Improvement included: endometrial evaluation (p=0,026), tumour rupture rate during surgery (p=0,010) and the global compliance of the surgery (p Conclusion Staging surgery provides a better assessment and an appropriate treatment of this rare tumors. According to this study, the implementation of a national network and guidelines dedicated to rare gynaecologic tumors seems to significantly improve the surgical management of the patients with GCT. Disclosure Nothing to disclose.

Introduction/Background In the Phase III SOLO1 first-line trial, maintenance therapy with the PARP inhibitor olaparib provided a substantial progression-free survival (PFS) benefit to advanced ovarian cancer (OC) patients who have a BRCA1/2 mutation (BRCAm) and are in complete or partial response to first-line chemotherapy (Moore K et al. N Engl J Med 2018). VEGF inhibitor may increase PARP sensitivity, particularly in some OC patients with BRCA wild type (Liu JF et al. Lancet Oncol 2014). PAOLA-1/ENGOT-ov25 (NCT02477644) is the first Phase III trial to evaluate the efficacy and safety of a PARP inhibitor with bevacizumab as first-line maintenance therapy, and in patients regardless of BRCAm status. Methodology PAOLA-1 is a randomized, double-blind, international Phase III trial. Eligible patients had newly diagnosed, advanced (FIGO stage IIIA-IV) high-grade serous or endometrioid ovarian, fallopian tube or peritoneal cancer. Patients had no evidence of disease or were in partial response following first-line platinum-based chemotherapy plus bevacizumab. Bevacizumab was to be given for up to 15 months, including the initial combination with chemotherapy. 806 patients were randomized (2:1) in maintenance therapy to olaparib (300 mg bid) or placebo plus bevacizumab (15 mg/kg, d1, q3w), stratified by first-line treatment outcome and tumour BRCAm status. The primary endpoint is investigator-assessed PFS (modified RECIST v1.1). The 458 PFS events required for the primary analysis to show significance at the two-sided 5% level with an estimated >80% power have been reached in March 2019. Database lock was in July and analyses are ongoing. Results The LBA will report: investigator-assessed PFS, PFS by BRCAm/HRD status, health- related quality of life, and safety and tolerability results. Conclusion PAOLA-1 will demonstrate whether addition of olaparib to bevacizumab maintenance therapy following first-line platinum-based chemotherapy plus bevacizumab provides a clinically meaningful benefit to OC patients. Disclosure P Harter declares honoraria from AstraZeneca, Roche, Sotio, Tesaro, Stryker, ASCO, Zai Lab and MSD; and consultancy/advisory board fees from AstraZeneca, Roche, Tesaro, Lilly, Clovis, Immunogen and MSD/Merck. Marie Ange Mouret-Reynier declares no conflicts of interest. S Pignata declares honoraria from Roche, AstraZeneca, MSD, Pfizer, Incyte, Novartis, PharmaMar, Clovis and Tesaro; and travel expenses from Roche, AstraZeneca and MSD. Claire Cropet declares no conflicts of interest. A Gonzalez-Martin declares consulting/advisory board fees from Roche, AstraZeneca, Tesaro, Clovis, Pfizer, ImmunoGen, PharmaMar, MSD, Genmad and Novartis; and speaker bureau/expert testimony fees from Roche, AstraZeneca, MSD Tesaro and PharmaMar. Gerhard Bogner declares consulting/advisory board fees from AstraZeneca Tesaro and Roche; and travel expenses from GSK, Roche, Pharmamar, AstraZeneca and Tesaro. K Fujiwara declares honoraria from AstraZeneca, Chugai Roche, Zeria, Taiho, Nihon Kayaku, Kyowahakko Kirin, Janssen and Daiichi Sankyo; consulting/advisory board fees from Pfizer, MSD and Eisai; research funding from AstraZeneca, MSD, Chugai Roche, Eisai and Kaken; and travel expenses from Pfizer. I Vergote declares consulting/advisory board fees from Advaxis, BIOCAD, Eisai, MSD, Roche, Genmab, Roche, PharmaMar, Millenium Pharmaceuticals, Clovis, AstraZeneca, Tesaro, Oncoinvent, ImmunoGen and Sotio; contracted research with Oncoinvent and Genmab; research funding from Amgen, Roche and Stichting tegen Kanker; and Takeda Oncology, PharmaMar, Genmab, Roche, AstraZeneca, Tesaro, Clovis and Immunogen. N Colombo declares honoraria from Roche, AstraZeneca, PharmaMar, Tesaro, Clovis, Pfizer, MSD, BIOCAD and Takeda; consulting/advisory board fees from Roche, AstraZeneca, PharmaMar, Tesaro, Clovis, Pfizer, MSD, BIOCAD, Takeda; and travel expenses from PharmaMar, Tesaro and Roche. J Maenpaa declares honoraria from Roche, AstraZeneca and Tesaro; consultancy/advisory board fees from AstraZeneca, Tesaro, Clovis and MSD; and travel expenses from Roche. Anne Floquet declares consultancy/advisory board fees from GSK, AstraZeneca and Clovis; and travel expenses from Roche, GSK and AstraZeneca. Ahmed El-Balat declares honoraria from AstraZeneca, Roche, Pharmamar, MSD, Tesaro, Clovis; and consultancy/advisory board fees from AstraZeneca and Roche. D Lorusso declares honoraria from Merck; consultancy/advisory board fees from Merck, AstraZeneca, Tesaro, Clovis, Immunogen, PharmaMar and Roche; research funding from Clovis, PharmaMar, Merck and Roche; and travel expenses from Tesaro, Roche and PharmaMar. EM Guerra Alia declares consultancy/advisory board fees from Roche, Clovis and AstraZeneca; and travel expenses from Roche and Baxter. Michel Fabro declares honoraria from Tesaro and AstraZeneca; and consultancy/advisory board fees from Tesaro and AstraZeneca. Barbara Schmalfeldt declares honoraria from Roche, AstraZeneca, Tesaro, Clovis, Ethicon, MSD; consultancy/advisory fees from Roche, AstraZeneca, Tesaro, Clovis, Ethicon, MDS; speaker bureau/expert testimony fees from Roche, AstraZeneca, Tesaro, Clovis, Ethicon, MDS; research grant funding from Roche, AstraZeneca, Tesaro, Clovis, Ethicon, MDS and travel expenses from Roche, AstraZeneca, Tesaro, Clovis, Ethicon, MDS. Anne Claire Hardy Blessard declares honoraria from AstraZeneca, Lilly, Novartis, Pfizer, Roche and Tesaro. Ingo Runnebaum declares honoraria from AstraZeneca. I Ray-Coquard declares honoraria from AstraZeneca, Clovis, Tesaro and PharmaMar; consulting/advisory board fees from AstraZeneca, Roche, Clovis, Tesaro, Genmab, PharmaMar, MSD and Pfizer; research funding from MSD; and travel expenses from AstraZeneca and Roche; consulting/advisory board fees from Roche; and travel expenses from Roche, MSD, Tesaro and AstraZeneca. E Pujade-Lauraine declares honoraria from AstraZeneca and Tesaro; consulting/advisory board fees from AstraZeneca, Roche, Clovis, Tesaro, Genmab, Incyte, MSD and Pfizer; research funding from AstraZeneca, Roche and Tesaro; and travel expenses from AstraZeneca, Roche and Tesaro.

Introduction/Background In SOLO1 (NCT01844986; GOG-3004), maintenance olaparib significantly improved progression-free survival (PFS) vs placebo (HR 0.30; 95% CI 0.23–0.41; P Methodology SOLO1 recruited patients who had undergone upfront or interval cytoreductive surgery and had no residual or residual macroscopic disease. Patients were stratified by platinum response (clinical CR or PR) and received olaparib tablets 300 mg twice daily or placebo. PFS was assessed by investigators using modified RECIST v1.1. Results 260 patients were randomized to olaparib and 131 to placebo; one patient did not receive placebo. Median follow-up was 41 months in both arms. 63% and 35% of patients underwent upfront and interval surgery, respectively; 76% and 21% had no residual and residual macroscopic disease, respectively, after surgery regardless of timing; and 44% of SOLO1 patients had stage III disease, underwent upfront surgery and had no residual disease following surgery. PFS was significantly improved with olaparib, regardless of the timing of surgery or residual disease status after surgery (table 1). PFS was also significantly improved in the subgroup of patients with stage III disease who underwent upfront surgery and had no residual disease following surgery. Conclusion Maintenance olaparib improved outcomes compared with placebo in patients with newly diagnosed advanced OC and a BRCAm, regardless of the timing of surgery or residual disease status after surgery. Olaparib improved PFS in stage III patients who had undergone upfront surgery and had no residual disease, a population at high risk of progression, but typically excluded from first-line OC trials. Disclosure KM: Ad board: AZ, Advaxis, Clovis, Tesaro, Genentech/Roche, Immunogen, VBL Therapeutics, Merck, Janssen, Aravive, Pfizer, Eisai, Samumed, Oncomed. NC: Honoraria/reimbursement, speaker role/advisory board fees: AZ, Roche, Tesaro, PharmaMar; advisory board fees: Clovis, Pfizer. GS: None. B-GK: None. AO: Consulting fees: Roche, AZ, PharmaMar, Clovis, Tesaro, Immunogen, Genmab. MF: Honoraria, speaker role/advisory boards: AZ; advisory board fees: MSD, Lilly, Takeda; non-comp consulting: AbbVie. AL: None. AF: Advisory board fees: AZ, Clovis; congress support: Roche, PharmaMar; advisory board fees/congress support: Tesaro. AL: Honoraria/reimbursement, advisory board fees: AZ; advisory board fees: Clovis, Biocad; consulting fees: Seattle Genetics. GS: Research funding: AZ, Merck, Novartis, Roche. CG: Honoraria/reimbursement, consulting fees, grants: AZ, Tesaro, Nucana; honoraria/reimbursement, consulting fees: Roche, Clovis, Foundation One, MSD, Sierra Oncology; grants: Novartis, Aprea. SB: Grants, honoraria/reimbursement: AZ; honoraria/reimbursement: Tesaro, Clovis, Merck, PharmaMar, Roche, Seattle Genetics. AO: Steering committee role (non-comp): AZ, Clovis, Tesaro. AG-M: Speaker role/consulting fees: AZ, Tesaro, PharmaMar, Roche; consulting fees: Clovis, Inmunogen, Genmab, Pfizer, MSD. CA: Honoraria/reimbursement: Tesaro, ImmunoGen, Clovis. WB: None. CM: None. JL: Advisory board fees: AZ, Clovis, Mersana, Tesaro. ESL: Shareholder, employee: AZ. RB: Shareholder, employee: AZ. PD: Consulting fees: AZ, Tesaro.

Purpose: Uterine leiomyosarcoma, which accounts for 7% of all soft-tissue sarcomas and 1%–3% of all uterine malignancies, is an aggressive tumor responsible for a significant proportion of uterine cancer–related deaths. While Federation Internationale des Gynaecologistes et Obstetristes (FIGO) stage is the most important prognostic factor, metastatic and relapse rates at stage I exceed 50% so it is currently impossible to predict the clinical outcome of stage I leiomyosarcomas. In 2010, our team published a transcriptomic signature composed of 67 genes related to chromosome biogenesis, mitosis control, and chromosome segregation. It has demonstrated its prognostic value in many cancer types and was recently successfully applied to formalin-fixed, paraffin-embedded sarcomas by NanoCind on NanoString technology, making another step forward toward its use in routine practice. Experimental Design: Sixty uterine leiomyosarcomas at any stage, including 40 localized in the uterus (stage I), were analyzed with the NanoCind (CINSARC with NanoString) signature. Its prognostic value was evaluated for overall survival and relapse-free survival and compared in multivariate analysis with other prognostic markers like FIGO staging and genomic index. Results: The NanoCind signature was able to split the heterogeneous group of uterine leiomyosarcomas of any stage including stage I into two distinct groups with different relapse-free survival and overall survival. These results were validated on an independent cohort of uterine leiomyosarcomas in The Cancer Genome Atlas consortium. Conclusions: The NanoCind signature is a powerful prognosticator that outperforms FIGO staging and the genomic index. The CINSARC signature is platform independent and “ready to use” and should now be used for randomization in future therapeutic trials.

The French national rare gynecological tumor network has been established to improve the quality of care through offering expertise in double reading histological diagnosis, reviewing cases and guiding management of these tumors through specialized multidisciplinary tumor boards and online clinical guidelines (www.ovaire-rare.com). The aim of this study is to evaluate the impact of the development and implementation of this network by assessing the conformity of medical practice with the guidelines concerning the granulosa cell tumors (GCTs).This is a French nationwide study, including 463 patients (out of the 639 identified patients) with a definitive diagnosis of GCT between 2011 and 2016. Surgical practices were analyzed for conformity with the current guidelines (www.ovaire-rare.org). Medical records, surgical and pathological reports were systematically analyzed. Total conformity was defined by a conservative (unilateral salpingo-oophorectomy) or radical surgery (hysterectomy and bilateral salpingo-oophorectomy) including surgical staging (omentectomy, peritoneal biopsies and peritoneal cytology) according to the FIGO stage. Partial conformity referred to a conservative or radical surgery without surgical staging and non-conformity was defined as a non-optimal surgery as recommended by the guidelines.Median age at diagnosis was 49 years old (range 10-89). The median size of tumor was 94 mm (range 5-400). Radical surgery was performed in 240 patients (52%); while a fertility-sparing surgery was performed in 98 cases (21%). A surgical staging was performed in 76 cases (16%) and an evaluation of the endometrium in 289 cases (62%). Surgery was fully compliant with the guidelines in 65 patients (14%), partially compliant in 213 patients (46%), non-compliant in 137 patients (30%) and not assessable in 48 cases (10%). A statistically significant difference for compliance was observed in restaging surgery (p 0,001), radical surgery (p = 0,017) and the period (before or after) of the implementation of the network (p 0,001). Survival analyses did not allow us to demonstrate a significant difference in overall survival nor in PFS although there was a trend in favor of optimal surgery compared to incomplete/non optimal surgery.Surgical management's conformity to the guidelines increases over time from 2011 to 2016. According to this study, the implementation of a national network dedicated to rare gynecologic tumors seems to significantly improve the surgical management of the patients with ovarian granulosa cell tumors.

The European Society of Gynaecologic Oncology (ESGO) guidelines cover the whole field of common clinical situations in gynecologic oncology. Their elaboration follows a strict process including a systematic review of the literature, the setting up of a group of expert on the basis of scientific production, geographical balance, and multidisciplinarity, and an external review by users and patients. The recommendations for the management of vulvar cancer were elaborated in 2015 and published in 2017. They are available in open access on the ESGO website, and can be incorporated in clinical practice using the free ESGO guidelines smartphone application. This review is a selection of the sections addressing the diagnostic and strategical aspects of the management of lymph nodal disease in vulvar cancer. An additional review of the recent literature published since 2015 has been carried out. The management of nodal disease in vulvar cancer encompasses a diagnostic and a therapeutic component. Clinical and imaging assessment still play a major role, whilst the identification of the sentinel node is currently a mainstay of assessment of the nodal status in early vulvar cancer. The therapeutic component is based on the rational use of full lymph node dissection and (chemo)radiation.

5508 Background: The Geriatric Vulnerability Score (GVS) combining albumin, lymphocyte count, ADL, IADL and HADS scores has been reported (Falandry C Ann Oncol 2013) to identify vulnerable elderly OC patients (pts) as those with a GVS≥3. For such pts, Carboplatin (Cb) monotherapy or weekly Cb plus paclitaxel (Pa) are often proposed as an alternative to Cb-Pa given every 3 weeks. Methods: Pts ≥70 yrs with first line FIGO stage III/IV epithelial OC were screened for GVS. Those with GVS≥3 were randomized to receive either arm A: Cb AUC5-6 + Pa 175mg/m², d1q3week or arm B: Cb AUC5-6 d1q3week or arm C:weekly Cb AUC2 + Pa 60mg/m² d1-d8-d15 q4week. Primary endpoint is treatment feasibility defined as the ability to complete 6 chemotherapy courses without disease progression, early treatment stopping due to unacceptable toxicity or death. Inclusion of 240 pts was planned. Results: Among 444 screened pts, 120 were randomized from 12/2013 to 04/2017 (armA = B = C = 40). Pts characteristics were well balanced between arms A-B-C respectively: median age (79-82-80 yrs), FIGO stage IV (32-37-27%), primary surgery (65-72-70%), absence of macroscopic residuals (CC-0) (7-5-7%), ECOG≥2 (50-50-47%). Feasibility per protocol for arms A-B-C is 65%, 47% and 60% (p = 0.15). Main reasons for treatment arrest are treatment toxicity (A:20%; B:15%; C:22.5%; p = 0.771) and disease progression (A:7.5%; B:30%; C:2%; p = 0.004). Median PFS for arm A-B-C are 12.5 mos (95%CI 10.3-15.3), 4.8 (3.8-15.3) and 8.3 (6.6-15.3), respectively (p < 0.001) and median OS for arm A-B-C is not reached (NR) (21, NR), 7.4 (5.3-NR) and 17.3 (10.8-NR), respectively (p = 0.001). At the pre-planned intermediate analysis, the IDMC recommended to prematurely close the study as survival in armB was found significantly worse and the number of potential pts required to find a significant difference between both Cb-Pa regimens (arms A&C) was out of reach. Conclusions: Compared to 3-weekly and weekly Cb-Pa regimens, Cb single agent was reported to be less active with significant worse survival outcome in vulnerable elderly pts. In this population Cb-Pa combination remains a standard. Clinical trial information: NCT02001272.

Few data are available on long-term fatigue (LTF) and quality of life (QoL) among epithelial ovarian cancer survivors (EOCS). In this case-control study, we compared LTF, symptoms and several QoL domains in EOCS relapse-free ≥3 years after first-line treatment and age-matched healthy women.EOCS were recruited from 25 cooperative GINECO centers in France. Controls were randomly selected from the electoral rolls. All participants completed validated self-reported questionnaires: fatigue (FACIT-F), QoL (FACT-G/O), neurotoxicity (FACT-Ntx), anxiety/depression (HADS), sleep disturbance (ISI), and physical activity (IPAQ). Severe LTF (SLTF) was defined as a FACIT-F score37/52. Univariate and multivariate logistic regressions were conducted to analyze SLTF and its influencing factors in EOCS.A total of 318 EOCS and 318 controls were included. EOCS were 63-year-old on average, with FIGO stage I/II (50%), III/IV (48%); 99% had received platinum and taxane chemotherapy, with an average 6-year follow-up. There were no differences between the two groups in socio-demographic characteristics and global QoL. EOCS had poorer FACIT-F scores (40 versus 45, P 0.0001), lower functional well-being scores (18 versus 20, P = 0.0002), poorer FACT-O scores (31 versus 34 P 0.0001), and poorer FACT-Ntx scores (35 versus 39, P 0.0001). They also reported more SLTF (26% versus 13%, P = 0.0004), poorer sleep quality (63% versus 47%, P = 0.0003), and more depression (22% versus 13%, P = 0.01). Fewer than 20% of EOCS and controls exercised regularly. In multivariate analyses, EOCS with high levels of depression, neurotoxicity, and sleep disturbance had an increased risk of developing SLTF (P 0.01).Compared with controls, EOCS presented similar QoL but persistent LTF, EOC-related symptoms, neurotoxicity, depression, and sleep disturbance. Depression, neuropathy, and sleep disturbance are the main conditions associated with severe LTF.

Introduction Rare ovarian tumours include complex borderline ovarian tumours, sex-cord tumours, germ cell tumours and rare epithelial tumours. Indications and modalities of fertility preservation (FP), infertility management, contraindications for hormonal contraception or menopause hormone therapy are frequent issues in clinical practice. A panel of experts from the French national network dedicated to rare gynaecological cancers, and experts in reproductive medicine and gynaecology have built guidelines on FP, contraception and menopause hormone therapy in women treated for ovarian rare tumours. Material and methods A panel of 35 experts from different specialties contributed to the preparation of the guidelines, following the DELPHI method (formal consensus method). Statements were drafted after a systematic literature review and then rated through two successive rounds. Results Thirty-five recommendations were identified, concerning indications for FP, contraindications for ovarian stimulation, contraceptive options and menopause hormone therapy for each tumour type. Discussion Overall, caution has been recommended in the case of potentially hormone-sensitive tumours such as sex-cord tumours, serous and endometrioid low-grade adenocarcinomas, as well as for high-risk serous borderline ovarian tumours. Conclusion In the context of a scarce literature, a formal consensus method allowed the elaboration of guidelines, which will help clinicians in the management of these patients.

Background: There is a lack of information as to which molecular processes, present at diagnosis, favor tumour escape from standard-of-care treatments in cervical cancer (CC). RAIDs consortium (www.raids-fp7.eu), conducted a prospectively monitored trial, [BioRAIDs (NCT02428842)] with the objectives to generate high quality samples and molecular assessments to stratify patient populations and to identify molecular patterns associated with poor outcome. Methods: Between 2013-2017, RAIDs collected a prospective CC sample and clinical dataset involving 419 participant patients from 18 centers in seven EU countries. Next Generation Sequencing has so far been carried out on a total of 182 samples from 377 evaluable (48%) patients, allowing to define dominant genetic alterations. Reverse phase protein expression arrays (RPPA) was applied to group patients into clusters. Activation of key genetic pathways and protein expression signatures were tested for associations with outcome. Findings: At a median FU of 22 months, progression-free survival rates of this FIGO stage IB1-IV population, treated predominantly (87%) by chemoradiation, were 65*4% [CI95%: 60*2-71.1]. Dominant oncogenic alterations were seen in PIK3CA (40%), while dominant suppressor gene alterations were seen in KMT2D (15%) and KMT2C (16%). Cumulative frequency of loss-of-function (LOF) mutations in any epigenetic modulatorgene alteration was 47% and it was associated with PIK3CA gene alterations in 32%. Patients with tumours harbouring alterations in both pathways had a significantly poorer PFS. A new finding was the detection of a high frequency of gains of TLR4 gene amplifications (10%), as well as amplifications, mutations, and non-frame-shift deletions of Androgen receptor (AR) gene in 7% of patients. Finally, RPPA protein expression analysis defined three expression clusters. Interpretation: Our data suggests that patient population may be stratified into four different treatment strategies based on molecular markers at the outset. Funding: European Union's Seventh Program grant agreement No 304810. Declaration of Interest: All authors declared: No conflict of interest. Ethical Approval: Ethical review was conducted according to national requirements and in accordance with the Declaration of Helsinki. All tumour and serum samples and clinical data were registered in a common database using a unique barcode system assuring data privacy.

5522 Background: There is a medical unmet need for effective treatments in platinum resistant ovarian cancer patients. We assessed the safety and efficacy of a combination of pembrolizumab with bevacizumab and pegylated liposomal doxorubicin (PLD). Methods: This is an open-label phase 1b trial in patients ECOG 0 or 1 with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. The safety of the dual combinations of pembrolizumab with bevacizumab or with PLD were previously evaluated in 6 patients respectively. In the absence of dose limiting toxicities (DLT) the triple combination was evaluated at a maximum tolerated dose (MTD)-1 for PLD in 3 patients and in the absence of DLT at MTD. The sample size was calculated according to the modified toxicity probability interval design. The primary evaluation criteria was the safety, the secondary endpoint was the outcome. Pharmacokinetics of the flat dose of bevacizumab will be evaluated. Results: 22 patients were enrolled from September 2019 until June 2020 in six French centers. 3 initial patients have been treated at 20mg/m2 of PLD (MTD-1) and 19 patients were treated at the dose of 30mg/m2 of PLD (MTD) combined with 200mg of pembrolizumab until progression, unacceptable toxicity, or withdrawal of consent and 400mg of bevacizumab for a total of six cycles. The patients’ characteristics are reported in the table. No DLT occurred. Grade 3 palmar-plantar erythrodysesthesia were reported in 4 patients. The recommended phase II dose of PLD was 30mg/m2 in combination with pembrolizumab and bevacizumab. For patients treated at MTD, the overall response rate was 32% (6 partial responses) with 74% of clinical benefit with a durable response in 10 patients (53%). Median number of cycles was 7.5 (2 to not reached). Two patients are still on treatment. Correlative studies are ongoing. Conclusions: The combination was well tolerated and demonstrated clinical benefit in 74% platinum resistant ovarian cancer patients with durable response (>6 months) in 53% of patients. Clinical trial information: NCT03596281. [Table: see text]

Importance To our knowledge, this is the first randomized trial in sex cord-stromal tumors, and it establishes weekly paclitaxel as standard-of-care therapy after platinum-based therapy in this setting. Objective To determine the efficacy of weekly paclitaxel with or without bevacizumab as treatment for relapsed sex cord-stromal tumors and evaluate whether the addition of bevacizumab to weekly paclitaxel improves 6-month progression-free rate. Design, setting, and participants This open-label, academic, international, randomized phase 2 trial (ALIENOR) was conducted at 28 referral centers in France, Germany, Italy, Japan, and Belgium in collaboration with the Rare Tumor committee of the Gynecologic Cancer InterGroup and used an adaptive bayesian design. It included 60 women with sex cord-stromal tumors that had relapsed after at least 1 platinum-based chemotherapy. Enrollment occurred from 2013 to 2016, and the final analysis database lock was on March 27, 2020 (median follow-up, 38.9 months). Interventions Participants were randomized to receive either paclitaxel (80 mg/m2, days 1, 8, and 15 every 4 weeks) alone or paclitaxel with bevacizumab (10 mg/kg, every 2 weeks) for 6 cycles followed by maintenance bevacizumab (15 mg/kg, every 3 weeks) for up to 1 year or until progression or unacceptable toxicity. Crossover to bevacizumab was permitted after progression during or following paclitaxel alone. Main outcomes and measures Six-month progression-free rate. Results Sixty patients (predominantly with granulosa cell tumors) were randomized, 32 to receive single-agent paclitaxel (median [interquartile range] age at inclusion, 60 [53-64] years) and 28 to receive paclitaxel-bevacizumab (median [interquartile range] age at inclusion, 55 [47-61] years; 1 did not receive treatment). The estimated 6-month progression-free rate was 71% (95% credible interval, 55%-84%) with paclitaxel alone and 72% (95% credible interval, 55%-87%) with paclitaxel-bevacizumab. The bayesian estimate for the probability that the 6-month progression-free rate distribution was higher with the combination than with paclitaxel alone was 57%, less than the predefined superiority threshold. The objective response rate increased from 25% (95% CI, 12%-43%) to 44% (95% CI, 26%-65%) with the addition of bevacizumab. One patient discontinued combination therapy within 6 months because of toxicity. Conclusions and relevance Weekly paclitaxel is a new option for relapsed sex cord-stromal tumors. In this international randomized clinical trial of patients with relapsed sex cord-stromal tumors unsuitable for surgery, adding bevacizumab to weekly paclitaxel does not improve clinical benefit. Trial registration ClinicalTrials.gov Identifier: NCT01770301.

Community forestry, promoted as a “win–win” forest management strategy yielded a variety of results that includes both failure and relative success. The willingness of government to hold control over forest resources while transferring only part of property rights to local communities is one of the major constraints. Therefore, there is a need to explore alternative approaches, which enhance the position and accountability of local communities in community forest management. This study evaluated socio-economic and ecological outcomes of community forestry in a context of important property rights conceded to local communities. The study was conducted using focus groups discussions, forest income evaluation and assessment of forest resources and their dynamics. Findings showed that institutional design with important property rights conceded to local communities partially empowered local communities and reduced threats while improving the condition of forest resources. The approach also yielded positive economic outcomes that enabled bordering populations to make up to 25% of their global annual income from the forest. However, the sustainability of this scheme of forest management was mostly limited by the financial dependency on local non-governmental organization, by local institutions and discrepancy in forest benefits sharing among local forest users.

6023 Background: Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), is a rare and rapidly lethal disease affecting young women with over half dying within 2 years of diagnosis. We previously reported improved outcomes with cytoreductive surgery followed by HDC-aSCR in a prospective study, but these encouraging results needed to be confirmed in an independent and larger cohort. Methods: Between 2008 and 2019, out of 44 patients (pts) diagnosed with centrally confirmed SCCOHT in 16 referent centers of the TMRG network, 38 were treated prospectively according to the French recommendations of the network with complete surgery (primary or after neoadjuvant chemotherapy), 4 to 6 cycles of PAVEP chemotherapy (cisplatin, doxorubicin, vepeside, and cyclophosphamide), and for pts with complete response (CR), HDC-aSCR, followed by pelvic radiotherapy. The 6 patients who could not receive PAVEP (unfit or diagnostic delay) relapsed and died rapidly. The primary endpoint was the event-free survival (EFS) in the intention-to-treat cohort. Results: Median age at diagnosis was 33 years (14-76). 13 pts presented with FIGO stage I, 17 stage III and 6 stage IV, 2 unknown. Median follow-up was 55.5 months. 34 patients achieved CR with CT + surgery and 30 received HDC-aSCR (40%, 47% and 10% with stages I, III and IV diseases respectively) and 21 received also pelvic radiotherapy. Median overall and event-free survival was 36.4 and 15.9 months respectively, and 2-years event-free survival rate was 40% (CI95% 25-56). Median OS was respectively not reached, 18 and 9.6 months for FIGO I, III and IV patients. Among the pts (N = 14) who did not receive HDC-aSCR (rapid progression during or after PAVEP), the 2-yr EFS was 0% compared to 50.5% for the 30 patients receiving HDC. In multivariate analysis, HDC was significantly correlated with better outcomes (p < 0.001). For the 21 patients receiving also pelvic radiotherapy, 57% (12/21) are free of recurrence at 4 years. Grades 3/4 adverse events were frequent (78%) but, in most cases, manageable, although one toxic death (3%) occurred during HDC (fungal septic shock). Conclusions: Treatment of SCCOHT, with intensive multimodal therapy, is associated with a 40% 2-yr event-free survival. However, this protocol is associated with significant toxicity and should be restricted to good performance status patient and expert centers.

11506 Background: U-LMS and ST-LMS are rare tumors with poor prognosis when locally advanced or metastatic, and with moderate chemosensitivity. Overall response rates (ORR) given in the 1st-line setting do not exceed 50% for U-LMS and 35% for ST-LMS with a mean response duration of 3- 6 months without impact on overall survival (OS). In 2015 we reported very encouraging results of the LMS-02 study (NCT02131480) with ORR of 59.6% in U-LMS, and 39.3% in ST-LMS with manageable toxicity (Pautier; Lancet oncol 2015). Herein, we report the updated results of progression-free survival (PFS) and final results of overall survival (OS). Methods: Patients (pts) received 60 mg/m² intravenous Doxo followed by trabectedin 1.1 mg/m2 as a 3-hour infusion on Day 1 and pegfilgrastim on Day 2, repeated every 3 weeks for up to 6 cycles. Surgery for residual disease was permitted. Patients were stratified into U-LMS and ST-LMS groups. Results: Overall, 108 patients with LMS with a median age of 59 years and mostly metastatic disease (85%) were enrolled. Of those, 77 patients (71.3%) have received all 6 cycles of treatment, and 20 patients (18.5%) had metastasis resection. With a median follow-up of 7.2 years (95% CI: 6.9 - 8.2), the overall median PFS was 10.1 months (95% CI: 8.5 - 12.6), being 8.3 months (95 CI: 7.4 - 10.3) and 12.9 months (95% CI: 9.2 - 14.1) in U and ST group, respectively. Median OS was 34.4 months (95% CI: 26.9 - 42.7), being 27.5 months (95% CI: 17.9 - 38.2) in U-LMS and 38.7 months (95% CI: 31.0 - 52.9) in ST-LMS group. The median OS among the 20 pts with surgery was not reached vs 31.6 months in the population without surgery (95% IC: 23.9 - 35.4). Conclusions: The Doxo +Trab combination is an effective 1st-line therapy for pts with LMS, with promising PFS and OS results and an acceptable safety profile. Merely for comparison, the most recent results of Doxo alone in metastatic LMS, given in 1st-line setting in a phase III ANNOUNCE trial conducted during the same period, reported median PFS of 6.9 months, and median OS of 21.9 months (ASCO 2019 LBA3). Results of the LMS04 trial (NCT02997358), a randomized phase III study comparing this combination vs Doxo alone in 1st-line therapy in metastatic LMS are pending. Clinical trial information: NCT02131480 .

TPS6109 Background: Advanced endometrial cancer (EC) patients relapse despite treatment with combination chemotherapy and have a short progression-free survival (PFS). Data from the TGCA suggest opportunities to targeting DNA repair in women with EC. Particularly type 4 (High copy number or serous like, with frequent TP53 mutations) and type 2 (microsatellite instability hypermutated) EC can be associated with defects in double strand break DNA repair by homologous recombination (HR) and could potentially be targeted by olaparib. We propose a placebo-controlled, multicenter, two-arm, phase II trial comparing olaparib versus placebo in maintenance therapy after chemotherapy in patients with advanced/metastatic EC. Methods: The primary objective of this trial is to evaluate the efficacy of maintenance olaparib in comparison to placebo after platinum based chemotherapy, defined by PFS according to Recist. Key eligibility criteria include: advanced/metastatic histologically confirmed EC (excepted carcino-sarcoma, small cells& neuroendocrine); prior surgery, adjuvant chemotherapy, radiation and hormonal therapy are permitted; objective or stable response after first-line chemotherapy is mandatory. 147 patients are randomized (2:1) after chemotherapy to receive Olaparib 300mg twice daily or placebo in maintenance after at least 4 cycles of platinum based chemotherapy. Olaparib/placebo is continued until disease progression, unacceptable toxicity, or withdrawal. Stratification is on IHC P53 and MMR status. Primary hypothesis is a 66.7% relative increase in the median PFS rate in the olaparib arm (from 4.5 to 7.5 months), corresponding to a 0.60 Hazard Ratio. Secondary endpoints include PFS according to P53, MMR and NGS HRD status, PFS2, disease specific survival, time to subsequent therapy, overall survival, objective response, disease control rate, patient reported outcomes (assessed via EORTC QLQ-C30 and EORTC QLQ-EN24, EORTC-FA, EQ5D) and safety. Trial is recruiting in France (in February n= 40 randomization). Conclusion: this will be the first study that evaluate the efficacy of olaparib in maintenace after chemotherapy in advanced/metastastic EC, stratified on molecular profil. Clinical trial information: NCT03745950.

Poly(ADP-ribose)polymerase (PARP) inhibitors are targeted therapy for cancers with homologous repair deficiency (HRD). They were first approved for ovarian cancer and have changed current treatment strategies. They have also demonstrated efficacy in HER2-negative metastatic breast cancer and advanced prostate cancer with BRCA1/2 or ATM mutations. Patients with somatic and/or germline BRCA1/2 mutations benefit more from these treatments than other patients. Nowadays, the diagnosis of HRD is largely based on germline genetic testing, which is performed after an in-person genetic counseling session, even for patients without any family history of cancer. However, with the increasing number of PARP inhibitor indications across different tumor types, rapid access to oncogenetic consultations will become a challenge. To meet this demand, tumor genomic testing could be offered at initial diagnosis. Telephone counseling and other referral systems could replace in-person consultations for certain subgroups of patients deemed to have a low risk of harboring a germline mutation. This article reviews international guidelines for genetic counseling testing. We herein propose new care pathways for breast, prostate and ovarian cancers, including tumor genomic testing at initial diagnosis in order to help triage genetic counseling referrals.

© 2017 Elsevier Ltd Background Poly(ADP-ribose) polymerase (PARP) inhibitors have activity in ovarian carcinomas with homologous recombination deficiency. Along with BRCA1 and BRCA2 (BRCA) mutations genomic loss of heterozygosity (LOH) might also represent homologous recombination deficiency. In ARIEL2, we assessed the ability of tumour genomic LOH, quantified with a next-generation sequencing assay, to predict response to rucaparib, an oral PARP inhibitor. Methods ARIEL2 is an international, multicentre, two-part, phase 2, open-label study done at 49 hospitals and cancer centres in Australia, Canada, France, Spain, the UK, and the USA. In ARIEL2 Part 1, patients with recurrent, platinum-sensitive, high-grade ovarian carcinoma were classified into one of three predefined homologous recombination deficiency subgroups on the basis of tumour mutational analysis: BRCA mutant (deleterious germline or somatic), BRCA wild-type and LOH high (LOH high group), or BRCA wild-type and LOH low (LOH low group). We prespecified a cutoff of 14% or more genomic LOH for LOH high. Patients began treatment with oral rucaparib at 600 mg twice per day for continuous 28 day cycles until disease progression or any other reason for discontinuation. The primary endpoint was progression-free survival. All patients treated with at least one dose of rucaparib were included in the safety analyses and all treated patients who were classified were included in the primary endpoint analysis. This trial is registered with ClinicalTrials.gov, number NCT01891344. Enrolment into ARIEL2 Part 1 is complete, although an extension (Part 2) is ongoing. Findings 256 patients were screened and 206 were enrolled between Oct 30, 2013, and Dec 19, 2014. At the data cutoff date (Jan 18, 2016), 204 patients had received rucaparib, with 28 patients remaining in the study. 192 patients could be classified into one of the three predefined homologous recombination deficiency subgroups: BRCA mutant (n=40), LOH high (n=82), or LOH low (n=70). Tumours from 12 patients were established as BRCA wild-type, but could not be classified for LOH, because of insufficient neoplastic nuclei in the sample. The median duration of treatment for the 204 patients was 5·7 months (IQR 2·8–10·1). 24 patients in the BRCA mutant subgroup, 56 patients in the LOH high subgroup, and 59 patients in the LOH low subgroup had disease progression or died. Median progression-free survival after rucaparib treatment was 12·8 months (95% CI 9·0–14·7) in the BRCA mutant subgroup, 5·7 months (5·3–7·6) in the LOH high subgroup, and 5·2 months (3·6–5·5) in the LOH low subgroup. Progression-free survival was significantly longer in the BRCA mutant (hazard ratio 0·27, 95% CI 0·16–0·44, p

Mesenchymal neoplasms of the uterus (corpus and cervix) encompass a heterogeneous group of tumors with differing morphologies, immunophenotypes and molecular alterations. With the advent of modern molecular techniques, such as next generation sequencing, newly defined genetic abnormalities are being reported in this group of neoplasms. Herein we report the clinicopathological and molecular features of a series of 13 spindle cell sarcomas of the uterus and vagina (10 cervix, 2 uterine corpus, 1 vagina) with morphology resembling fibrosarcoma. After targeted RNA-sequencing, dual FISH fusion and array-CGH analysis, 7 of 13 tumors exhibited NTRK rearrangements (6 TPM3-NTRK1 and 1 EML4-NTRK3) and 3 a COL1A1-PDGFB fusion; in the other 3 neoplasms, all of which were positive with S100 (2 diffuse, 1 focal), we identified no rearrangement. All the NTRK fusion-positive sarcomas were located in the cervix and exhibited diffuse staining with Trk while all the other neoplasms were negative. CD34 was diffusely positive in all 3 of the COL1A1-PDGFB fusion sarcomas. The latter molecular abnormality is identical to that commonly found in dermatofibrosarcoma protuberans and has not been reported previously in uterine mesenchymal neoplasms. We suggest that uterine sarcomas with a morphology resembling fibrosarcoma (and in which leiomyosarcoma and the known molecularly confirmed high-grade endometrial stromal sarcomas have been excluded) can be divided into 3 groups:- an NTRK fusion group, a COL1A1-PDGFB fusion group and a group containing neither of these molecular abnormalities which, on the basis of positive staining with S100, could be tentatively classified as malignant peripheral nerve sheath tumor, although additional molecular studies may identify specific genetic alterations necessitating a nomenclature change. We suggest a diagnostic algorithm when reporting such neoplasms. Identification of these newly described fusion-associated sarcomas is important given the potential for targeted treatments.

Introduction Onapristone is a type I progesterone receptor (PR) antagonist, which prevents PR- mediated DNA transcription. Onapristone is active in multiple preclinical models and two prior studies demonstrated promising activity in patients with breast cancer. We conducted a study of extended release (ER) Onapristone to determine a recommended dose and explore the role of transcriptionally-activated PR (APR), detected as an aggregated subnuclear distribution pattern, as a predictive biomarker. Methods An open-label, multicenter, randomized, parallel-group, phase 1 study (target n = 60; NCT02052128) included female patients ≥18 years with PRpos tumors. APR analysis was performed on archival tumor tissue. Patients were randomized to five cohorts of extended release (ER) onapristone tablets 10, 20, 30, 40 or 50 mg BID, or immediate release 100 mg QD until progressive disease or intolerability. Primary endpoint was to identify the recommended phase 2 dose. Secondary endpoints included safety, clinical benefit and pharmacokinetics. Results The phase 1 dose escalation component of the study is complete (n = 52). Tumor diagnosis included: endometrial carcinoma 12; breast cancer 20; ovarian cancer 13; other 7. Median age was 64 (36–84). No dose limiting toxicity was observed with reported liver function test elevation related only to liver metastases. The RP2D was 50 mg ER BID. Median therapy duration was 8 weeks (range 2–44), and 9 patients had clinical benefit ≥24 weeks, including 2 patients with APRpos endometrial carcinoma. Conclusion Clinical benefit with excellent tolerance was seen in heavily pretreated patients with endometrial, ovarian and breast cancer. The data support the development of Onapristone in endometrial endometrioid cancer. Onapristone should also be evaluated in ovarian and breast cancers along with APR immunohistochemistry validation.

Background In SOLO1 (NCT01844986; GOG-3004), maintenance olaparib significantly improved PFS vs placebo (HR 0.30; 95% CI 0.23–0.41; Moore et al. NEJM 2018) in patients with newly diagnosed advanced OC, a BRCA mutation and clinical complete or partial response after platinum-based chemotherapy. Most patients in the maintenance setting are well following first-line treatment; thus, it is important to show that extending PFS is not at the expense of decreased health-related quality of life because of toxicity. We assessed the duration of ‘good quality of life’ while on maintenance therapy based on time without significant symptoms of toxicity (TWiST) and quality-adjusted PFS (QAPFS) which both incorporate the adverse effects experienced by patients on maintenance therapy. Methods Patients were randomized 2:1 to olaparib tablets 300 mg bid or placebo. Patient-centred outcomes were assessed by QAPFS (product of adjusted mean estimate of the EuroQol 5D-5L single-index utility score from randomization to disease progression and mean PFS time) and TWiST (period without significant symptoms post-randomization and before disease progression or censoring for progression) in a post hoc analysis in the full analysis set. Results Of 391 randomized patients, 260 received olaparib and 130 placebo (1 patient did not receive placebo). Mean QAPFS and TWiST improved to a clinically meaningful extent with olaparib vs placebo, with highly significant between-group improvements of at least 12 months (Table). Table . 224O Olaparib Placebo QAPFS n = 260 n = 131 Mean duration (95% CI), months 29.75 (28.20–31.63) 17.58 (15.05–20.18) Between-group difference (95% CI), months 12.17 (9.07–15.11) P value P TWiST * n = 260 n = 131 Mean duration (95% CI), months 33.15 (30.82–35.49) 20.24 (17.36–23.11) Between-group difference (95% CI), months 12.92 (9.30–16.54) P value P * TWiST is the time without significant symptoms of toxicity, defined as grade ≥2 nausea, vomiting or fatigue. Conclusions There were clinically meaningful patient-centred benefits with maintenance olaparib in both QAPFS and TWiST supporting the substantial benefit of PFS improvement seen with olaparib in newly diagnosed advanced OC. Clinical trial identification NCT01844986. Editorial acknowledgement Medical writing assistance was provided by Gillian Keating, MBChB, from Mudskipper Business Ltd, funded by AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (MSD). Legal entity responsible for the study AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (MSD). Funding AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Disclosure M.L. Friedlander: Honoraria (self), Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: MSD; Advisory / Consultancy: Lilly; Advisory / Consultancy: Takeda; Advisory / Consultancy, Uncompensated: AbbVie. K.N. Moore: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Advaxis; Advisory / Consultancy: Clovis; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy: Immunogen; Advisory / Consultancy: VBL Therapeutics; Advisory / Consultancy: Merck; Advisory / Consultancy: Janssen; Advisory / Consultancy: Aravive; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Eisai; Advisory / Consultancy: Samumed; Advisory / Consultancy: Oncomed. N. Colombo: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Tesaro; Honoraria (self), Advisory / Consultancy: PharmaMar; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Immunogen; Advisory / Consultancy: Biocad; Advisory / Consultancy: Seattle Genetics. A. Oaknin: Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: PharmaMar; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Immunogen; Advisory / Consultancy: Genmab. A. Floquet: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy, Congress support: Roche; Advisory / Consultancy, Congress support: PharmaMar; Advisory / Consultancy, Congress support: Tesaro. A. Leary: Honoraria (self), Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Biocad; Advisory / Consultancy: Tesaro; Advisory / Consultancy: MSD; Advisory / Consultancy: GamaMabs; Advisory / Consultancy: Seattle Genetics. G.S. Sonke: Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Merck; Research grant / Funding (self): Novartis; Research grant / Funding (self): Roche. C. Gourley: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Tesaro; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Nucana; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Clovis Oncology; Honoraria (self), Advisory / Consultancy: Foundation One; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Sierra Oncology; Honoraria (self), Advisory / Consultancy: Cor2Ed; Research grant / Funding (self): Novartis; Research grant / Funding (self): Aprea. S. Banerjee: Honoraria (self), Research grant / Funding (self): AstraZeneca; Honoraria (self): Tesaro; Honoraria (self): Clovis Oncology; Honoraria (self): Merck; Honoraria (self): PharmaMar; Honoraria (self): Roche; Honoraria (self): Seattle Genetics; Honoraria (self): Nucana. A. Oza: Non-remunerated activity/ies, Steering Committee: AstraZeneca; Non-remunerated activity/ies, Steering Committee: Clovis Oncology; Non-remunerated activity/ies, Steering Committee: Tesaro. A. Gonzalez-Martin: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Tesaro; Advisory / Consultancy: PharmaMar; Advisory / Consultancy: Roche; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Immunogen; Advisory / Consultancy: Genmab; Advisory / Consultancy: Pfizer; Advisory / Consultancy: MSD. C. Aghajanian: Honoraria (self): Tesaro; Honoraria (self): ImmunoGen; Honoraria (self): Clovis Oncology. E. Lowe: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. R. Hettle: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. E. Flood: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. P. Disilvestro: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Tesaro. All other authors have declared no conflicts of interest.

Background Nintedanib is a multikinase inhibitor whose main targets are VEGFR 1/2/3, PDGFR and FGFR1. It is approved for idiopathic pulmonary fibrosis and non-small-cell lung cancer. The randomized phase II CHIVA trial tested it as an add-on to chemotherapy in the neo-adjuvant/adjuvant setting in advanced ovarian cancer eligible for debulking surgery. We report a nintedanib exposure-response relationship in the nintedanib arm. Methods Data from 122 pts in the nintedanib arm were available. A population pharmacokinetic model could not be used, due to the sampling schedule (mostly trough concentrations). Therefore, raw serum nintedanib values were used as indicative of exposure. An ascending step-wise multivariate Cox model building strategy was used, without any a priori requirement for exposure to be in the final model, starting from 26 possible predictors. The outcome of interest (response) was overall survival. The existence and optimal value of a threshold was investigated using effect size and model likelihood with different thresholds. HRs and 95% CI are reported for each variable in the final model. Exposure-safety analyses on grade 3-4 and grade 4 adverse events were performed using similar model-building strategies in time-to-event analyses (Cox models) and in per-visit analyses (logistic models). Sensitivity analyses tested the robustness of the findings. Results The final model included average serum nintedanib, ECOG status, resection score, histological type, and renal function. The HR for death per extra 30 ng/mL average serum nintedanib was 0.61 (95% CI, 0.41-0.92). The threshold with highest model likelihood and highest effect on survival was around 50-55 ng/mL(100 nM), which is in the range of known IC50 values for nintedanib targets. 75% of pts were below this value, 25% were below 12 ng/mL. No exposure-safety relationships were found. Conclusions An exposure-response relationship was found for nintedanib in ovarian cancer. These exploratory results suggest that while it is difficult to maintain consistent nintedanib exposure, survival gains could reward success on that front. Future nintedanib trials may benefit from therapeutic drug monitoring with a threshold trough concentration of 100 nM. Clinical trial identification 2011-006288-23. Legal entity responsible for the study ARCAGY-GINECO. Funding Boehringer Ingelheim. Disclosure N. Dohollou: Research grant / Funding (institution): Roche; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Lilly. A. Floquet: Advisory / Consultancy, Travel / Accommodation / Expenses: Tesaro; Advisory / Consultancy: Clovis; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Roche. C. Louvet: Advisory / Consultancy: MSD; Advisory / Consultancy: Roche; Advisory / Consultancy: Halozyme; Advisory / Consultancy: Servier; Advisory / Consultancy: AstraZeneca; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: MSD. J.E. Kurtz: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Takeda; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: PharmaMar; Travel / Accommodation / Expenses: Tesaro. P. Follana: Advisory / Consultancy: Novartis; Advisory / Consultancy: AstraZeneca; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: AstraZeneca; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: Tesaro. M. Leheurteur: Speaker Bureau / Expert testimony: Pfizer; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Eisai. J. Alexandre: Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self): Ipsen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self): PharmaMar; Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen. All other authors have declared no conflicts of interest.

Background The GINECO previously developed the GVS to identify geriatric vulnerability in oOC pts (Falandry, 2013). The derivation cohort was EWOT-3 database of 111 oOC pts treated with first line carboplatin. The GVS combines albumin (≥ or Methods Pts ≥70 yrs diagnosed with FIGO stage III/IV epithelial OC and no organ failure were screened for GVS. Those with GVS≥3 were proposed EWOC-1 randomized trial, evaluating 3 treatment regimens in the vulnerable pts. Other pts’ data were collected in the “EWOC-1 registry”. External validation of GVS was performed in the whole population (V1), in the EWOC-1 registry subgroup (V2), and in the subgroup of pts treated with carboplatin paclitaxel regimens (V3). Cross-validation analyses (calibration, discrimination, and performance analysis) were performed according current recommendations (Steyerber, 2014). Results From 12/2013 to 11/2018, 447 elderly patients were included, 120 (27%) in EWOC-1 trial and 327 in EWOC-1 registry (V1: n = 447, V2: n = 327, V3: n = 324). Patients’ cancer characteristics were similar in the validation cohorts compared to the derivation one. Median follow up was 22 mo; missing values were limited ( Conclusions GVS provides a reproducible and robust prediction model of vulnerability in oOC pts, independent of geographic and historic effect (V1), as well as treatment patterns (V3), validated on an international population. Clinical trial identification PROTOCOL EWOC-1 - ENGOT OV-23 - 2013-000266-11. Legal entity responsible for the study Centre Hospitalier Lyon Sud. Funding Hospital Clinical Research Program (PHRC). Disclosure D. Lorusso: Honoraria (self), Honoraria (institution), Advisory / Consultancy: MERCK; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Leadership role, Research grant / Funding (self): Clovis; Advisory / Consultancy: Immunogen; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Licensing / Royalties, Full / Part-time employment: PharmaMar; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Licensing / Royalties, Full / Part-time employment: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Licensing / Royalties, Full / Part-time employment: Tesaro; Officer / Board of Directors, Spouse / Financial dependant, Non-remunerated activity/ies: GCIG. A. Floquet: Advisory / Consultancy: Clovis; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Tesaro; Travel / Accommodation / Expenses: Roche. O. Tredan: Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): Novartis; Honoraria (self): Lilly; Honoraria (self): BMS; Honoraria (self): MSD. E. Pujade-Lauraine: Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Leadership role, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses, Shareholder / Stockholder /: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Leadership role, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Licensing / Royalties, Full: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Leadership role, Research grant / Funding (self): Clovis; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Leadership role, Research grant / Funding (institution), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time e: Tesaro; Advisory / Consultancy, Speaker Bureau / Expert testimony, Leadership role, Research grant / Funding (self): Genmab; Advisory / Consultancy, Speaker Bureau / Expert testimony, Leadership role, Research grant / Funding (self): Incyte; Advisory / Consultancy, Speaker Bureau / Expert testimony, Leadership role, Research grant / Funding (self): MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Leadership role, Research grant / Funding (self): Pfizer. C. Falandry: Honoraria (self): Leo Pharma; Honoraria (self), Honoraria (institution): Pfizer; Honoraria (self): MSD oncology; Honoraria (self): Teva; Honoraria (self): AstraZeneca; Honoraria (self): Baxter; Honoraria (self): Eisai; Honoraria (self): Janssen; Honoraria (self): Novartis; Honoraria (institution): Chugai Pharma; Honoraria (institution): Pierre Fabre; Honoraria (institution): Astellas Pharma. All other authors have declared no conflicts of interest.

Ovarian small cell carcinoma of the hypercalcemic type (SCCOHT)/ovarian rhabdoid tumor is a rare and highly malignant tumor that typically occurs in young women. Up until now the diagnosis has been made on the basis of morphology without any specific immunohistochemical (IHC) markers. However, several authors have shown recently that SCCOHTs are characterized by inactivation of the SMARCA4 gene (encoding the BRG1 protein) resulting in a loss of BRG1 protein expression in IHC. We evaluated BRG1 and INI1 expression in 12 SCCOHTs and in a series of 122 tumors that could mimic SCCOHT morphologically: 9 juvenile granulosa cell tumors, 47 adult granulosa cell tumors, 33 high-grade ovarian serous carcinomas, 9 desmoplastic round cell tumors, 13 Ewing sarcomas (5 from the pelvis and 8 from soft tissues), 1 round cell sarcoma associated with CIC-DUX4 translocation from soft tissue (thigh), 1 case of high-grade endometrial stromal sarcoma of the ovary, and 9 melanomas. Forty-four adult granulosa cell tumors were interpretable by IHC. All 12 SCCOHTs were devoid of BRG1 expression and expressed INI1. All other interpretable 119 tumors showed BRG1 nuclear positivity, with variable staining proportions, ranging from 10% to 100% of positive cells (mean: 77%, median: 80%), variable intensities (weak: 5%, moderate: 37%, strong: 58%), and distributions: diffuse in 82 cases (70%) and heterogenous in 36 cases (30%). BRG1 positivity was heterogenous in desmoplastic round cell tumors and adult granulosa cell tumors. Overall, BRG1 is a useful diagnostic marker in SCCOHT, showing the absence of expression in SCCOHT. Nevertheless, the possible heterogeneity and the variable intensity of this staining warrant caution in the interpretation of BRG1 staining in biopsy specimens.

Purpose: EGFR is frequently overexpressed in cervical cancer, suggesting EGFR blockade as a promising treatment approach. Cetuximab, an anti EGFR antibody, used conjointly with radiochemotherapy, was feasible in first-line treatment of cervix carcinoma limited to the pelvis. Experimental Design: This randomized phase II trial enrolled 78 FIGO stage IB2–IIIB cervical cancer patients to either cisplatin-based radiochemotherapy alone (arm B, n = 38) or conjointly with a 6-week course of weekly cetuximab (arm A, n = 40). Brachytherapy was given to the pelvic mass. Primary endpoint was disease-free survival (DFS) at 2 years. EGFR expression and targeted sequencing were performed in 54 of 78 patients. Results: Cetuximab over a 6-week period did not improve DFS at 24 months. At 31 months median follow-up, DFS was not significantly different (P = 0.18). Complete response at 4 to 6 months was strongly predictive for excellent DFS (log-rank test; P < 0.001). PIK3CA, KRAS, and STK11 mutations were observed in 22%, 4%, and 2% of patients, respectively. No tumor with a PI3K pathway mutation showed complete response (0/8 in arm A and 0/6 in arm B), whereas 14 of 52 (27%) tumors without mutations did (P = 0.021). PI3K pathway-mutated tumors showed a trend toward poorer DFS (P = 0.06) following cetuximab (8/22) as compared with those following standard treatment only (6/18). Conclusions: Similar to patients with head and neck cancer, patients with cervical cancer showed no gain in DFS at 2 years following a combined treatment of cetuximab with radiochemotherapy. Although treatment tolerance and compliance were satisfactory, it remains to be demonstrated whether maintenance therapy with cetuximab could be beneficial in selected patient groups. Clin Cancer Res; 21(11); 2530–7. ©2015 AACR.

The consumption frequency, the consumer’s income, the specific quality attribute and the consent to pay Agonlin oil, an oil of high standard made with a traditional knowledge is transferred from generation to generation in Agonlin region. According to its attributes, this oil has been evaluated through 400 consumers from 5 different districts or municipalities. The data collected have been analyzed thanks to a descriptive analysis. All in all, 10 attributes have been identified: the flavor, color, consistency, taste, local and natural character, nutritional value, geographical origin, viscosity and texture. The descriptive analysis shows its taste (60%) as being the main attribute of Agonlin oil, followed by its flavor (51%). The majority of interviewers consume Agonlin oil many times in a week (59%). But the oil is consumed by people with low income (40000 to 75000 FCFA). Other consumers with average income agree to value Agonlin oil when it is well manufactured and conserved. This study shows that Agonlin oil is a traditional and original product that the consumers agree to value. Consequently, Agonlin oil rightly deserves a geographical indication protection. Key words: Quality attributes, geographical attribute, specific quality, consent to pay.