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Around 15% of metastatic endometrial carcinoma (EC) are MMRd/MSI-H improving response to immune checkpoint inhibitors (ICI). So far, few data existed considering the chemotherapy (CT) sensitivity in MMRd/MSI-H EC, especially response to first-line platinum-based treatment.We performed a multicentric retrospective analysis reporting the response to first line platinum CT in MMRd/MSI-H EC patients. The primary endpoints were objective response rate (ORR) and progression-free survival (PFS) with first line platinum-based CT.A total of 112 patients MMRd/MSI-H EC from 8 centers were identified. Median overall survival was 58.0 months (95% CI: 45.3-95.1). Among them, 78 patients received first line platinum CT in recurrent/metastatic setting. With a median follow up of 32.6 months (min: 0.03; max: 135.0), ORR and DCR (disease control rate) were 50% (95% CI: 38.5-61.5) and 68% (95% CI: 56.4-78.1), respectively. Median PFS and OS from first line platinum-based CT was 7.8 months (95% CI: 6.0-9.0) and 51.9 months (95% CI: 28.0-NE), respectively. Median PFS with ICI in second line (n = 48) was 10.7 months (95% CI: 3.4-NE) from ICI initiation.ORR in first line metastatic MMRd/MSI-H EC is consistent with efficacy in an all comer metastatic EC population.

Resume Objectifs La strategie de preservation de fertilite (PF) dans le cancer du col de l’uterus est challengee depuis plusieurs annees et une desescalade therapeutique semble s’imposer. Dans ce contexte, nous avons evalue les resultats oncologiques, de fertilite et obstetricaux des techniques chirurgicales realisees dans notre centre en vue d’une PF. Methodes Cet essai uni centrique retrospectif a inclus 75 patientes, prises en charge a l’institut Gustave Roussy entre 1995 et 2020, pour un cancer de col (stade IB1 FIGO 2018) et ayant conduit un projet de preservation de la fertilite apres un bilan pre-therapeutique approfondi. L’objectif d’un tel recueil etait d’apprehender nos resultats sur la fertilite et les issues obstetricales et les correler aux donnees oncologiques et enfin d’evaluer l’evolution de nos pratiques chirurgicales. Resultats Cinquante quatre patientes ont beneficie d’une trachelectomie elargie, aucune atteinte ganglionnaire n’a ete constatee. 1 patiente a recu un traitement complementaire en post operatoire ne permettant pas de preserver sa fertilite. Le taux de recidive etait de 4,8 % (4/75) avec un deces decrit. 31 grossesses ont ete obtenues soit un taux de grossesse de 50 %. 74 % des grossesses ont ete obtenues spontanement et 60 % des grossesses ont ete conduites a terme. Conclusion Nos resultats sont similaires a ceux de la litterature. Malgre un projet de preservation de fertilite seulement la moitie des patientes a pu obtenir une grossesse.

Resume L’evolution des connaissances en oncologie gynecologique conduit progressivement vers une desescalade chirurgicale dans plusieurs domaines, notamment dans celui de la chirurgie ganglionnaire. L’indication du ganglion sentinelle (GS) dans le cancer de l’endometre, initialement reserve aux risques bas et intermediaire, est maintenant elargie a tous les stades FIGO (International Federation of Gynecology and Obstetrics) I et II. Le GS a aussi une place tres importante dans la stadification ganglionnaire des cancers du col a un stade precoce. Par ailleurs, une reflexion importante est menee sur la radicalite des hysterectomies chez les patientes operees de cancer du col a un stade precoce. De meme, la stadification ganglionnaire lombo-aortique dans les cancers du col localement avances ne serait benefique qu’a une minorite de patientes. Les cancers de l’ovaire n’echappent pas a la desescalade chirurgicale avec une diminution des indications de lymphadenectomie.

Objective The randomized phase 3 CORAIL trial evaluated whether lurbinectedin improved progression-free survival (PFS) compared to pegylated liposomal doxorubicin (PLD) or topotecan in patients with platinum-resistant ovarian cancer. Methods Patients were randomly assigned (1:1) to lurbinectedin 3.2 mg/m2 1-h i.v. infusion q3wk (experimental arm), versus PLD 50 mg/m2 1-h i.v. infusion q4wk or topotecan 1.50 mg/m2 30-min i.v. infusion Days 1–5 q3wk (control arm). Stratification factors were PS (0 vs. ≥1), prior PFI (1–3 months vs. >3 months), and prior chemotherapy lines (1–2 vs. 3). The primary endpoint was PFS by Independent Review Committee in all randomized patients. This study was registered with ClinicalTrials.gov , NCT02421588 . Results 442 patients were randomized: 221 in lurbinectedin arm and 221 in control arm (127 PLD and 94 topotecan). With a median follow-up of 25.6 months, median PFS was 3.5 months (95% CI, 2.1–3.7) in the lurbinectedin arm and 3.6 months (95% CI, 2.7–3.8) in the control arm (stratified log-rank p = 0.6294; HR = 1.057). Grade ≥ 3 treatment-related adverse events (AEs) were most frequent in the control arm: 64.8% vs. 47.9% (p = 0.0005), mainly due to hematological toxicities. The most common grade ≥ 3 AEs were: fatigue (7.3% of patients) and nausea (5.9%) with lurbinectedin; mucosal inflammation (8.5%) and fatigue (8.0%) in the control arm. Conclusions The primary endpoint of improvement in PFS was not met. Lurbinectedin showed similar antitumor efficacy and was better tolerated than current standard of care in patients with platinum-resistant ovarian cancer.

Resume But de l’etude Le carcinome sereux de bas grade (CSBG) de l’ovaire est une entite distincte, d’evolution lente et touchant preferentiellement la femme jeune. L’objectif de cette etude est de decrire les caracteristiques cliniques et la survie d’une population de patientes atteintes de CSBG a un stade avance. Patients et methodes Il s’agit d’une etude retrospective, regroupant les patientes atteintes de CSBG de l’ovaire a un stade avance (FIGO IIIb-IV) ayant eu une chirurgie de cytoreduction macroscopiquement complete, prises en charge a l’Institut Gustave Roussy, Villejuif, entre 2004 et 2017. Resultats Trente-quatre patientes ont ete incluses. Il s’agissait de femmes jeunes (âge moyen 41,3 ans), ayant une maladie diagnostiquee au stade FIGO IIIc (91 %). Le suivi median etait de 41 mois. Une chimiotherapie neoadjuvante a ete administree chez 16 patientes (47,1 %), et n’a jamais permis d’obtenir une reponse complete. La chirurgie extensive comportait dans 90 % des cas un traitement de l’etage sus-mesocolique et dans plus de 80 % des cas une resection digestive. Plus de 90 % des patientes ont recu une chimiotherapie adjuvante, suivie de Bevacizumab en entretien dans plus de 40 % des cas. Au cours du suivi, 9 (26 %) deces sont survenus. La survie globale a 5 ans etait de 70 %, la survie sans recidive de 20 %. Conclusion Le CSBG de l’ovaire est un cancer peu chimiosensible et necessite une prise en charge chirurgicale maximale dans des centres experts.

Sarcoid-like granulomatosis (SLG) reaction caused by immunotherapy remains poorly understood. This study aims to investigate the outcome of patients with cancer and SLG associated with immunotherapy.Between April 2016 and June 2020, 434 patients with immunological adverse events were screened from the ImmunoTOX assessment board of Gustave Roussy, an academic cancer centre in France. Among them, 28 patients had SLG associated with immunotherapy (SLG cohort) and 406 patients had other immunological adverse events (control cohort). Clinical characteristics and outcome of patients were compared from SLG and control cohort.The SLG cohort consisted of 28 patients, 14 women and 14 men, with the median (range) age of 56.5 (28.7-75.3) years. Patients in the SLG cohort with sarcoidosis were asymptomatic (only radiographical finding) in 13 (46.4%) cases; otherwise, the most frequent symptoms were dyspnoea in 8 (28.6%) patients and cough in 5 (17.8%) patients. The computerised tomography scan found sarcoidosis localisations in mediastinal or peri-hilar thoracic lymph nodes in 26 (92.9%) patients, and lung parenchymal involvement was found in 14 (50.0%) patients. The radiographic Scadding stages for sarcoidosis classification were distributed in stages 0, I, II, III and IV in 2 patients (7.1%), 13 patients (46.4%), 11 patients (39.3%), 1 patient (3.6%) and 1 patient (3.6%), respectively. Compared with patients with other immunological toxicities (cohort control), patients with sarcoidosis presented most frequently with melanoma (75.0% versus 21.9% of patients; p 0.001) and more often received combined therapies of anti-programmed cell death 1 plus anti-cytotoxic T-lymphocyte antigen 4 protein (46.4% versus 12.6% of patients; p = 0.002). Patients with sarcoidosis had an improved overall survival (OS); the median OS was not reached in the SLG cohort and 40.4 months in the control cohort, hazard ratio = 0.232 (95% confidence interval: 0.086-0.630) (p = 0.002).Sarcoidosis-like reactions in patients receiving immunotherapy were reported as non-severe immunological reactions in most cases and were correlated with improved OS. SLG should not be misdiagnosed as tumour progression in patients receiving immunotherapy treatment for cancer.

Background The disappointing activity of single agent immune-checkpoint inhibitors in epitherlial ovarian cancer (EOC) has been attributed in part to its unique tumor microenvironment (TME). IDO, PDL1, LAG3 and TIM3 have been implicated in the immunotolerance of EOC. We investigated the expression of these co-regulators, their change with neoadjuvant chemotherapy (NACT), and their association with outcome. Method We identified 98 patients with EOC treated with NACT and performed IDO, PDL1, LAG3 and TIM3 immunohistochemistry on samples obtained before and after NACT. The cut-off threshold to consider a positive sample was set at 5%. Results In our cohort, TIM3 was the most prevalent co-regulator, with more than 75% of the samples being TIM3 positive. In comparison, only 22%, 28% and 17% of the samples were considered IDO, PDL1 and LAG3 positive. More than half of ovarian tumors expressed 2, 3 or even all 4 co-inhibitory molecules. However, biomarkers were not correlated with each other. NACT had a marked impact on immune co-regulator expression with over 70% of patients showing a change in biomarker status from negative to positive or vice versa. There was no significant difference in the pattern of co-regulator expression between platinum-sensitive and resistant patients. Co-expression of multiple inhibitory molecules did not appear to affect overall and progression-free survival. Conclusion TIM3 is the most abundant co-inhibitory molecule in OC and may represent an attractive target. In addition, OC frequently co-expressed 2 or more markers supporting ICI combinatorial approaches. Finally, NACT significantly altered the expression of immunosuppressive molecules suggesting that the choice of ICI combinations should be adapted to the composition of the post-NACT immune TME.

Small cell carcinoma of the ovary of hypercalcemic type (SCCOHT) is a rare and rapidly lethal disease affecting young women. Cytoreductive surgery associated with chemotherapy followed by a high dose chemotherapy regimen (HDC) demonstrated improved outcomes in a unique prospective and several retrospective studies, and this report aimed to confirm these results in an independent and larger cohort.Between 2006 and 2018, we conducted a multicentric prospective study on 44 women diagnosed with SCCOHT. Patients were treated homogeneously with optimal cytoreductive surgery and chemotherapy protocol for four to six cycles (PAVEP). In case of complete response, patients received HDC with stem-cell support, followed by pelvic radiotherapy. The primary endpoint was the event-free survival (EFS) in the per-protocol cohort. Secondary analysis explored the effect of HDC with outcomes.Mean age at diagnosis was 33 years old (range 13.8-75.8). 14 patients presented with stage FIGO I, 21 with stage III and 9 with stage IV. Median follow-up was 53.4 months. 38 patients underwent optimal surgery with up to 6 cycles of PAVEP. 30 received HDC, and 21 pelvic radiotherapy. 21 relapses were reported leading to death for 18 patients. Median EFS in the per-protocol cohort was 18.2 months, and 2-year EFS rate was 40%. HDC was significantly associated with better overall survival (p .001). Grades 3/4 adverse events were frequent but, in most cases, manageable, although one grade-5 adverse-event occurred during HDC.Intensive regimen containing multidrug chemotherapy, HDC and pelvic radiotherapy, for the management of SCCOHT, demonstrated encouraging survival and should be proposed for all patients. However, the significant toxicity cost associated is of concern and it should be restricted to expert centers.

Since dose escalation allowed by image-guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer (LACC), local relapses have become a rare event. Only scarce data are available on the outcome of patients experiencing a local relapse after IGABT.Between 2004 and 2016, all consecutive patients treated at Gustave Roussy Institute for LACC and receiving concomitant chemoradiation and IGABT were analysed. Clinical and treatment-related prognostic factors for survival after local relapse were searched, in order to potentially identify patients requiring salvage treatment.Two hundred and fifty-nine patients were treated during this period. With a median follow-up of 4.1 years, 10.8% (n = 28) had a local relapse. Among these patients, 53.6% had synchronous lymph nodes or distant metastatic relapse and only 13 patients (5% of all patients) had isolated local relapse. After local relapse, median survival was 47 months and three patients were alive at last follow-up. Only three patients with local relapse could receive salvage surgery (10.7%). Metastases occurrence and pelvic wall involvement were the main contraindications (67.9%) for salvage surgery. Among the three patients treated with surgery, two are still alive at last follow-up without significant complication. Improved survival was observed among the two patients who could have surgery (p = .02). Local progression led to serious symptoms in 75% of patients. Only the time interval between brachytherapy and relapse (1 year) was prognostic for 2-year overall survival (p = .005).Salvage surgery is feasible in a very low number of highly selected patients with local relapse following IGABT. Local failure is a major cause of severe local symptoms, confirming that every effort should be done to achieve long-term local control through dose escalation.

Resume De nombreuses femmes ayant ete traitees pour tumeur frontiere de l’ovaire (TFO) sont concernees par les questions de contraception et de traitement hormonal de la menopause ou substitutif (THM/THS). Objectifs Synthetiser les connaissances sur les risques de TFO lies a la contraception hormonale et au THM/THS, et emettre des recommandations sur la contraception et le THM/THS apres TFO. Methodes Revue systematique de la litterature concernant contraception hormonale et TFO et THM/THS et TFO (realisee sur PubMed/Medline et la Cochrane Library). Resultats Il n’existe pas de donnees concernant l’utilisation de contraception hormonale apres TFO. L’utilisation d’une contraception orale (ou un antecedent d’utilisation) est associee a une tendance a la reduction du risque de TFO sereuse, et a un effet moins marque voire neutre sur le risque de TFO mucineuse. L’utilisation de contraception hormonale apres une TFO sereuse ou mucineuse n’est ainsi pas contre-indiquee (grade C). Une tendance a l’augmentation du risque de TFO sereuse liee a la prise de THM/THS est retrouvee contrairement au risque de TFO mucineuse qui ne semble pas modifie (grade C). En cas d’antecedent de TFO presentant des criteres histologiques pejoratifs (contingent micropapillaire, micro-invasion, implants peritoneaux), compte tenu du risque accru de recidive sous forme infiltrante, hormonosensible, l’utilisation d’un THM/THS ne pourra etre envisagee qu’au cas par cas, avec prudence, apres discussion pluridisciplinaire. Apres traitement d’une TFO mucineuse ou sereuse sans criteres histologiques pejoratifs, un THM/THS peut etre utilise (grade C). Conclusion Les contraceptions hormonales peuvent etre utilisees apres TFO. Les caracteristiques histologiques de la tumeur doivent etre prises en compte pour decider de l’utilisation d’un THS/THM.

Summary Background Anti-programmed cell death 1 (PD-1) and anti-programmed cell death ligand 1 (PD-L1) antibodies are novel immunotherapies for cancer that can induce immune-related adverse events (irAEs). These adverse events can involve all organs, including the haemopoietic system. Thus far, haematological irAEs (haem-irAEs) have not been extensively characterised. This study aims to provide a comprehensive report of the haem-irAEs induced by anti-PD-1 or anti-PD-L1. Methods In this descriptive observational study, we included consecutive patients aged at least 18 years with grade 2 or worse haem-irAEs induced by anti-PD-1 or anti-PD-L1 immunotherapy registered in three French pharmacovigilance databases: the Registre des Effets Indesirables Severes des Anticorps Monoclonaux Immunomodulateurs en Cancerologie (REISAMIC; a prospective registry of patients treated with anti-PD-1 or anti-PD-L1 at a single centre), the ImmunoTOX committee of Gustave Roussy (a national referral database of suspected irAEs in patients treated with immunotherapy), and the registry of the Centre de Reference des Cytopenies Auto-Immunes de l'Adulte (CeReCAI; a national database of autoimmune cytopenias). Cases were reviewed by a central committee; adverse events had to be classed as certainly or probably related to anti-PD-1 or anti-PD-L1 therapy, and their severity was assessed according to the Common Terminology Criteria for Adverse Events (version 4.03). The primary endpoint was clinical description of haem-irAEs, as reported in all databases, and their frequency, as reported in the prospective REISAMIC registry. Findings We screened 948 patients registered in the three databases from June 27, 2014, to June 29, 2018 (745 from REISAMIC, 190 from the ImmunoTOX committee, and 13 from CeReCAI). 35 patients (21 men and 14 women) with haem-irAEs related to anti-PD-1 or anti-PD-L1 were included in the study. Of 745 patients in the REISAMIC registry treated with anti-PD-1 or anti-PD-L1, four had haem-irAEs, giving a frequency of 0·5%. Median age in the 35 patients was 65 years (IQR 51–75), and the most common tumour types were melanoma (15 [43%] patients), non-small-cell lung cancer (12 [34%] patients), and lymphoma (four [11%] patients). 20 (57%) patients received nivolumab, 14 (40%) received pembrolizumab, and one (3%) received atezolizumab. Among the 35 patients, neutropenia, autoimmune haemolytic anaemia, and immune thrombocytopenia were the most common types of haem-irAE (each in nine patients [26%]), followed by pancytopenia or aplastic anaemia (five patients [14%]), bicytopenia (one patients with thrombocytopenia plus anaemia and one patient with neutropenia plus anaemia [6%]), and pure red cell aplasia (one patient [3%]). The maximum grade of severity was grade 2 in three (9%) patients, grade 3 in five (14%) patients, and grade 4 in 25 (71%) patients; two (6%) patients died from febrile neutropenia during haem-irAE related to anti-PD-1. Haem-irAEs resolved in 21 (60%) of the 35 patients. Interpretation Haem-irAEs induced by PD-1 or PD-L1 inhibitors are rare but potentially life-threatening events. The most common clinical presentations are neutropenia, autoimmune haemolytic anaemia, immune thrombocytopenia, and aplastic anaemia. Investigations into earlier detection and better management are warranted. Funding Gustave Roussy and Gustave Roussy Immunotherapy Program.

During the recent past years, the therapeutic management of locally advanced cervical cancer patients has consistently improved, with the integration of image guided brachytherapy and dose escalation strategies leading to an improvement of local control rates. In parallel, the evolution of external beam radiotherapy techniques and the better control of organs at risk doses in brachytherapy have contributed to decrease the probability of severe normal tissue complication. In case of advanced disease, patients prognosis remains however marked by a high risk of distant failure, and this finding has encouraged the assessment of various research pathways in order to better predict and/or prevent tumor relapse. Major studies are being conducted or have been published, and the place of chemoradiation and brachytherapy has been confirmed as first intent treatment in case of locally advanced disease. Numerous prospective or retrospective data, few of which are reviewed there, have been integrated as part of a strategy aimed at being more and more personalized. Next steps of therapeutic optimization will include the assessment of multiparameters radiological tools, but will also rely on a better understanding of radiobiological pathways involved in local or systemic response to irradiation, and the most promising of those is probably the anti-tumor immune response.

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.

Objectives: In the PAOLA-1/ENGOT-ov25 primary analysis (NCT02477644), adding the PARP inhibitor olaparib to maintenance bevacizumab (bev) after first-line platinum-based chemotherapy with bev led to a significant progression-free survival (PFS) benefit vs placebo (pbo) + bev in patients (pts) with advanced high-grade ovarian cancer (HGOC), using modified RECIST v1.1 criteria (HR 0.59; 95% CI 0.49-0.72; P Methods: Pts with newly diagnosed, FIGO stage III-IV HGOC in response after platinum-based chemotherapy plus bev received bev (15 mg/kg q3w for 15 months) + olaparib (300 mg bid for 24 months) or pbo. Scans were performed every 24 weeks, or every 12 weeks if there was evidence of clinical or CA-125 progression. CA-125 levels were assessed every 12 weeks. Time to RECIST or CA-125 progression or death was a secondary endpoint; RECIST/CA-125 progression by biomarker status, response to initial therapy and CA-125 level at baseline were explored. Results: 537 pts were randomized to olaparib + bev and 269 to pbo + bev with median follow-up for PFS by RECIST/CA-125 of 24.2 vs 24.7 months (DCO 22 March 2019). In the ITT population, the benefit provided by olaparib + bev vs pbo + bev for PFS by RECIST/CA-125 (HR 0.58; 95% CI 0.48-0.70; P Download : Download high-res image (258KB) Download : Download full-size image Conclusions: Median PFS and HRs were consistent when progression was assessed by either RECIST or RECIST/CA-125 in PAOLA-1. Scans appear particularly important for detecting progression in HRD-positive pts, tBRCAm pts or pts with normal CA-125 levels at baseline as CA-125 levels did not seem to predict relapse in these pts. Results suggest that CA-125 surveillance alone may be sufficient to detect progression in most pts with abnormal baseline CA-125 levels when starting maintenance therapy.

Resume Le cancer de l’endometre presente generalement une evolution favorable quand il est diagnostique a un stade precoce, mais reste de mauvais pronostic en situation avancee (metastatique ou en rechute), avec peu d’options therapeutiques. L’hormonotherapie est le traitement de choix en cas de maladie lentement evolutive, et lorsque la tumeur exprime les recepteurs hormonaux. Les taxanes, les anthracyclines et les sels de platine sont les molecules de chimiotherapie les plus actives, avec des taux de reponses augmentes en cas d’association, au prix d’une toxicite non negligeable. Des therapeutiques ciblees basees sur une meilleure connaissance de la biologie tumorale sont en cours de developpement clinique, avec des resultats parfois prometteurs, surtout en association. Il est important de connaitre, pour choisir au mieux le traitement, les comorbidites associees frequentes dans cette population, les caracteristiques histologiques precises (type histologique, grade, expression des recepteurs hormonaux, et statut des proteines de reparation des mesappariements de base [statut MSI]) pour une decision therapeutique adaptee.

Rare adult cancer (RAC) is characterised by an incidence of less than six cases per 100,000 people per annum; 4,300,000 patients in the European Union are living with rare cancer (22% of all new human cancers). These cancers are linked with worse survival rates than ‘frequent’ tumours (5-year survival: 47% for RAC against 65% for ‘common’ cancers), mainly because of: (1) delays in obtaining an accurate diagnosis, (2) inadequate treatments given in curative phases and (3) restricted opportunities for patients to participate in clinical trials because of the lack of support for dedicated trials for this disease group from both academic and industrial sponsors. Although quantitative studies to measure the socioeconomic burden of RACs as a whole are still lacking, the increasing fragmentation of all cancers into molecular subgroups implies a substantial increase in the number of RACs and their associated socioeconomic burden. To answer this urgent and growing need, some countries, cooperative groups, and cancer institutes delineated national and/or regional organisations to promote quality management for RACs. Currently, the European Union (EU) is supporting an official EU call to organise a European network dedicated to RACs. The goals will be to pool the vast knowledge and expertise of the 67 EU clinical reference centres and to cover ten rare adult solid cancer domains across more than 18 countries in order to deploy an integrated, EU-wide capacity towards accelerated innovative treatments and care for RACs while empowering patients. This article will summarise these experiences and the potential benefit for patients.

Since the last two decades, the feasibility of fertility-sparing surgery (FSS) in early-stage epithelial ovarian cancer (EOC) has been explored by several teams and is reconsidered in this systematic review undertaken using the PRISMA guidelines. Borderline ovarian tumours and non-EOCs were excluded. This review comprises 1150 patients and 139 relapsing patients reported by 21 teams. This conservative treatment can be safely carried out for stage IA and IC grade 1 and 2 disease and stage IC1 according to the new FIGO staging system. Nevertheless, the number of patients reported with grade 2 disease is too small to definitively confirm whether FSS is safe in this subgroup. For patients with 'less favourable' prognostic factors (grade 3 or stage IC3 disease), the safety of FSS could not be confirmed, but patients should be informed that radical treatment probably may not necessarily improve their oncological outcome, because the poorest survival observed could be related to the natural history of the disease itself and not specifically to the use of conservative therapy. FSS could probably be considered in stage I clear-cell tumours but should remain contraindicated for stage II/III disease (whatever the histologic subtype). As the disease stage and the histologic data (tumour type and grade) are crucial to patient selection for this treatment, this implies careful and mandatory complete surgical staging surgery in this context and a pathological analysis (or review) of the tumour by an expert pathologist.

Background. Anti-programmed death (ligand) 1 (PD-(L)1) antibodies are novel immunotherapies for cancer. Anti-PD(L)1 can induce immune-related adverse events (irAEs), which most frequently affect the skin, endocrine glands, lung, liver and digestive tract, however all organs including the hematopoietic system can potentially be involved. Hematologic irAEs (hem-irAEs) have not yet been extensively characterized. This study based on a pharmacovigilance academic registry aims to provide a comprehensive report of hem-irAEs. Patients and methods. All grade 2 or higher hem-irAEs recorded in pharmacovigilance databases were recorded in this study over the period 2013-2018. Pharmacovilance database included REISAMIC (Registre des Effets Indesirables Severes des Anticorps Monoclonaux Immunomodulateurs en Cancerologie) and ImmunoTOX committee of Gustave Roussy, and the French nationwide CeReCAI registry (Centre de Reference des Cytopenies Auto-Immunes de l'adulte). Prevalence of hem-irAE was calculated in the prospective REISAMIC registry. The hem-irAE's severity was assessed according to the Common Terminology Criteria for Adverse Events (version 4.03). Results. Thirty-five patients (21 men and 14 women) with hem-irAEs related to anti-PD(L)1s were recorded. The prevalence of grade ≥2 hem-irAEs among patients treated with anti-PD(L)1s was estimated to 0.54%. The patients' median age was 65 years (range: 30-90), tumor types were melanoma (n=15), non-small-cell lung carcinoma (n=12), lymphoma (n=4), and other types (n=4). A concomitant medical history of chronic lymphocytic leukemia was found in 3 (9%) patients. The hem-irAEs were classified as neutropenia (n=9; 26%), auto-immune hemolytic anemia (n=9; 26%), immune thrombocytopenia (IT) (n=9; 26%), pancytopenia or aplastic anemia (n=5; 14%), bicytopenia (n=2; 6%) and pure-red cell aplasia (n=1; 3%). The maximum grade of severity reported was grade 2 in 3 (9%) patients, grade 3 in 8 (23%) patients and grade 4 in 24 (69%) patients. Two patients (6%) had a poor outcome and died in the course of the hem-irAE. Treatments given for the hem-irAE were steroids in 31 (89%) patients, granulocyte colony-stimulating factor in 13 (37%) patients, intravenous immunoglobulins in 6 (17%) patients and rituximab in 2 (6%) patients. The median time to onset from anti-PD(L)1 initiation was 10.1 weeks (range 0.9 - 198.0). With a median follow-up of 19 (range 2-180) weeks, the rate of resolution of hem-irAE was 67% (78% for IT and 40% for aplastic anemia patients, p=0.524). After resolution, 6/35 (17%) patients were rechallenged and 3 of them (50%) recurred the same hem-irAE. Conclusion. The clinical spectrum of hematologic irAE is wide and dominated by neutropenia, hemolytic anemia and immune thrombocytopenia. Aplastic anemia is rarer and present as a life-threatening condition. The prevalence of grade ≥2 hematologic irAEs following anti-PD(L)1 was 0.54%. The recurrence rate after rechallenge was 50%. Further prospective investigations are warranted to better detect and manage hematologic immune-related adverse events. Funding: This academic study was supported by Gustave Roussy Declaration of Interest: Nicolas Delanoy: none, Jean-Marie Michot: Advisory board: Bristol-Myers Squibb, Thibaut Comont: none, Nora Kramkimel: none, Julien Lazarovici : none, Romain Dupont : none, Stephane Champiat : none, Caroline Robert: Advisory board: Bristol-Myers Squibb, Charles Herbaux: none, Benjamin Besse : none, Claude Chahine : none, Aude Guillemin : none, Christine Mateus : none Ethical Approval: The REISAMIC registry was approved by ethical committee and the institutional review board of Gustave Roussy.

Background The response to ICI in cervical cancer remains modest and predictive biomarkers to select patients (pts) are needed. An IPI score combining lactate dehydrogenase (LDH) level and the derived neutrophils/ (leucocytes minus neutrophils) ratio (dNLR) has been shown to correlate with ICI outcome in melanoma and lung cancer. We aimed to assess the predictive value of baseline IPI for advanced cervical cancer treated with ICI. Methods Pre-ICI treatment dNLR and LDH were retrospectively collected for all pts with advanced cervical cancer treated at our institution with PD1/PDL1 inhibitors (n = 48). Patients were divided into three groups: IPI-0 (normal LDH, dNLR upper limit or dNLR>3), and IPI-2 (LDH>upper limit and dNLR>3). The primary endpoint was overall survival (OS) and the secondary objective was progression free survival analyzed by Kaplan Meyer and log-rank (PFS). Results In our cohort of 48 pts, 37 (77%) had squamous histology, median age was 47 (range 21 to 76), and 46 (95%) had performance status of 0 or 1. Among the 14 pts with papilloma virus (HPV) testing, 100% were HPV+. PDL1 expression >1% was detected in 9 of 13 patients tested (69%). Most patients were previously treated with at least one line of previous systemic therapy (92%). The majority were treated in phase 1 trials (n = 37) and 25 received ICI in combination with antiangiogenic therapy or another ICI. 22 patients were IPI-0, 22 IPI-1, and 4 IPI-2. Median OS and PFS for our cohort were 14.7 and 3.4 months, respectively. Median PFS in the three groups was 4.9 months, 2.6 months and 0.6 months, respectively (p = 0.004). Median OS was 19.3, 10.4, and 0.9 for IPI 0, 1, and 2, respectively (p = 0.003). OS was 8.9 months for patients who received ICI as monotherapy, whereas OS for the combination group had not yet been reached. Conclusions Baseline IPI was highly correlated with ICI-treated cervical cancer pt outcomes. Pts with higher IPI had poorer survival and are likely worse candidates for ICI, particularly as monotherapy. IPI score should be considered in addition to PDL1 status before introducing ICI in patients with advanced cervical cancer. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure F. Blanc-Durand: Speaker Bureau / Expert testimony: Janssen Cylag; Travel / Accommodation / Expenses: Pfizer. P. Pautier: Travel / Accommodation / Expenses, Officer / Board of Directors: AstraZeneca; Travel / Accommodation / Expenses, Officer / Board of Directors: Roche; Travel / Accommodation / Expenses, Officer / Board of Directors: Tesaro; Officer / Board of Directors: MSD; Officer / Board of Directors: Clovis. C. Massard: Advisory / Consultancy: Amgen; Advisory / Consultancy: Astellas; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Bayer; Advisory / Consultancy: Beigene; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy: Celgene; Advisory / Consultancy: Debiopharm; Advisory / Consultancy: Genentech; Advisory / Consultancy: Ipsen; Advisory / Consultancy, Research grant / Funding (institution): Janssen; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy, Research grant / Funding (institution): Medimmune; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Advisory / Consultancy: Orion; Research grant / Funding (institution): Boehringer; Research grant / Funding (institution): Merck. A. Leary: Advisory / Consultancy, Travel / Accommodation / Expenses, PI: Tesaro; Advisory / Consultancy, Travel / Accommodation / Expenses, PI: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses, PI: Clovis; Advisory / Consultancy, PI: Gammamabs; Advisory / Consultancy, Pi: Grindstone; Advisory / Consultancy, Pi: Seattle Genetics; Advisory / Consultancy, PI: Pfizer; Advisory / Consultancy, PI: MSD; Advisory / Consultancy, PI: BMS. All other authors have declared no conflicts of interest.

La quimioterapia ocupa un lugar primordial en el tratamiento de los carcinomas ovaricos epiteliales, tanto en los estadios tempranos como en los avanzados. El esquema de referencia asocia carboplatino y paclitaxel por via intravenosa. En los estadios avanzados y despues de una cirugia completa, la via intraperitoneal ha demostrado tambien su eficacia en el tratamiento de primera linea, pero debe reservarse a los equipos experimentados, debido a sus dificultades tecnicas y a la toxicidad de la que puede ser responsable. En caso de recaida o de progresion, las modalidades de la quimioterapia dependen principalmente del intervalo libre entre este diagnostico y la ultima inyeccion de platino. El bevacizumab ha demostrado su eficacia prolongando la supervivencia libre de progresion en tratamiento de primera linea, asociado a quimioterapia y luego en mantenimiento, asi como en las recaidas o progresiones tanto sensibles como resistentes a los platinos. Finalmente, un mejor conocimiento de la biologia del cancer de ovario permitira considerar en el futuro tratamientos personalizados guiados por las caracteristicas especificas de cada paciente y cada tumor.

Recent advances have been made in the molecular profiling of gynecological tumors. These discoveries have led to the development of targeted therapies that have the potential to disrupt molecular pathways involved in the oncogenesis or tumor progression. In this review, we highlight areas of recent progress in the field of membrane receptor inhibitors in gynecological malignancies and describe the biological rationale underlying the inhibition of these receptors. We will introduce drug immuno-conjugates, and give an update on the biological rationale and the clinical studies involving agents directed against EGFR, HER3, IGFR, MET, FGFR, NOTCH, and TRAIL. We also discuss the challenge facing these new therapies.

Background Patients with high-risk gestational trophoblastic neoplasia (GTN) need multi-agent chemotherapy to be cured. The most common regimen is etoposide (E), methotrexate (M) and actinomycin D (A), alternating weekly with cyclophosphamide (C) plus vincristine (O) (EMA/CO). Cisplatin (P) is a very active drug, but it is usually restricted to second-line therapies. Herein, we report the results of a cisplatin-based therapy: APE (actinomycin D, cisplatin, and etoposide). Patients and methods The efficacy and safety of APE for high-risk GTN (defined by Institut Gustave-Roussy (IGR) criteria and/or an International Federation of Gynaecology and Obstetrics (FIGO) score >6) are reported. Patients with brain metastasis or placental-site trophoblastic tumour were excluded. Results Between 1985 and 2013, 95 patients were treated with APE for high-risk GTN: 59 patients as first-line, 36 as ⩾2nd-line therapy. There was 94.7% complete remission, though five patients relapsed. One patient died from GTN after multiple lines of chemotherapy. The five-year overall survival rate (median follow-up 5.7 years) was 97% (95% confidence interval (CI): 91–99%). No death from toxicity occurred. Long-term, six grade-1 neuro-toxicities, three grade-1 and two grade-2 oto-toxicities, and one grade-1 renal toxicity were recorded. One patient developed AML-M4 after APE and EMA/CO. Thirty-four of 35 women, who wished to become pregnant, succeeded and all had at least one live birth. Conclusion With a 97% long-term overall survival rate, limited long-term toxicity, and an excellent reproductive outcome, APE could be regarded as an alternative option to EMA/CO as a standard therapy for high-risk GTN.

Doublet chemotherapy with cisplatin is the reference for the treatment of recurrent cervical cancer. However, those tumors are little chemo-sensitive and overall survival remains poor. Moreover, because of pelvic irradiation, toxicities, especially hematologic toxicities, are increased and require a drug dose reduction. Finally, these treatments are rarely effective in radiation areas. Given all these elements, the development of new therapies is a prominent issue. This article reviews the results of the major targeted therapies in cervical cancer. Anti-EGFRs are disappointing despite of a strong biological rational. On the other hand, bevacizumab is the first targeted therapy to show a significant increase of overall survival. A major effort must be made in translational research for a better understanding of tumor biology of these tumors.

Background Most borderline ovarian tumors (BOTs) are cured with surgery. However BOTs with invasive implants have a poor prognosis with a mortality of 20–40%. The benefit of adjuvant chemotherapy (CT) in this setting remains poorly defined. Methods Retrospective study of serous BOT+invasive implants treated with adjuvant CT. Results 36 patients were referred with serous BOTs+invasive implants and treated with surgery and platinum-based CT between 06/1982 and 02/2011. 83% were stage III/IV. Tumors demonstrated microinvasion, micropapillary pattern or desmoplastic implants in 53%, 47% and 67% of cases, respectively. 8% had fertility-sparing surgery. Taking into account initial and completion surgeries, R0 was achieved in 84% (27/32) (NA, N=4). The majority (72%) received a combination of platinum+taxane. 11% of patients experienced a G3/G4 toxicity. 13 of 36 (36%) patients relapsed at a median of 27.3months after diagnosis of invasive implants. Among 12 patients with histologically confirmed relapse, 8 patients progressed with invasive disease in the form of carcinoma or invasive implants. 5year PFS/OS were 67%/96%. Neither microinvasion, micropapillary pattern, nor desmoplastic implants predicted relapse. In cases with evaluable disease, an objective response to chemotherapy was observed in 4 of 6 patients. Conclusion This is the largest study of BOT with invasive implants treated with surgery and adjuvant platinum-based CT. Treatment was well tolerated and the invasive relapse rate was 22% (8/36). Although numbers are small, the objective responses suggest a possible role for adjuvant CT in BOTs with invasive implants.

Background Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer and is often diagnosed at advanced stages. The current standard of care (SOC) for advanced EOC is primary debulking surgery (PDS) followed by adjuvant carboplatin/paclitaxel chemotherapy (CT). Although SOC may be effective initially, most patients experience relapse within 3 years after treatment. Combination therapy with PD-1 inhibitor pembrolizumab (pembro) plus PARP inhibitor niraparib resulted in efficacy in patients with platinum-resistant, relapsed OC in the phase 1/2 study TOPACIO/KEYNOTE-162. The PARP inhibitor olaparib is approved for women with newly diagnosed BRCA-mutated OC, as well as for platinum-sensitive, recurrent OC regardless of BRCA1/2 status. Pembro plus CT followed by olaparib maintenance therapy is being investigated in ENGOT-ov43/KEYLYNK-001 (NCT03740165), a phase 3, randomized, double-blind, active- and placebo-controlled study for first-line treatment of women with BRCA1/2-nonmutated advanced EOC. Trial design Women with stage III or IV BRCA-nonmutated EOC, primary peritoneal cancer, or fallopian tube cancer will be randomized 1:1:1 after one lead-in cycle of CT to receive pembro + CT followed by olaparib maintenance; pembro + CT followed by placebo; or placebo + CT followed by placebo. Stratification factors include surgery status (residual tumor after PDS [yes/no] or planned interval debulking), planned bevacizumab use (yes/no), and PD-L1 combined positive score (CPS; Clinical trial identification NCT03740165. Legal entity responsible for the study Merck & Co., Inc. Funding Funding for this study was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Disclosure K. Fujiwara: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Chugai Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Eisai; Advisory / Consultancy, Research grant / Funding (institution): Merck Sharpe & Dohme Corp.; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Taiho Pharmaceutical; Advisory / Consultancy: Takeda; Honoraria (self): Bayer; Honoraria (self): Daiichi Sankyo; Honoraria (self): Janssen Oncology; Honoraria (self): Kyowa Hakko Kirin; Honoraria (self), Research grant / Funding (institution): Lilly Japan; Honoraria (self): Nippon Kayaku; Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self): Zeria Pharmaceutical; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Immunogen; Research grant / Funding (institution): Kaken Pharmaceutical; Research grant / Funding (institution): Oncotherapeutics; Research grant / Funding (institution): Shionogi. I.B. Vergote: Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Eisai; Advisory / Consultancy, Travel / Accommodation / Expenses: PharmaMar; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Advaxis; Advisory / Consultancy: Merck Sharp & Dohme Corp.; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Genmab; Advisory / Consultancy: Millennium Pharmaceuticals; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Immunogen; Advisory / Consultancy, Travel / Accommodation / Expenses: TESARO, Inc.; Advisory / Consultancy, Research grant / Funding (institution): Oncoinvent; Advisory / Consultancy: Roche; Advisory / Consultancy: Sotio; Travel / Accommodation / Expenses: Takeda; Research grant / Funding (institution): Amgen. J. Sehouli: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self): Eisai; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Clovis; Honoraria (self): Olympus; Honoraria (self): JohnsonJ Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: PharmaMar; Honoraria (self): Teva Pharmaceutical Industries Ltd.; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: TESARO, Inc.; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Sharpe & Dohme Corp.; Advisory / Consultancy: Lilly; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche. P. Zola: Advisory / Consultancy, Travel / Accommodation / Expenses: TESARO, Inc.; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Research grant / Funding (self): Roche. R.M. Wenham: Research grant / Funding (self), Shareholder / Stockholder / Stock options: Ovation Diagnostics; Advisory / Consultancy, Speaker Bureau / Expert testimony: TESARO, Inc.; Advisory / Consultancy: Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony: Clovis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Genentech; Advisory / Consultancy: Mersana Therapeutics; Research grant / Funding (self): TapImmune; Research grant / Funding (self): Merck; Research grant / Funding (self): Prescient Therapeutics. P. Pautier: Advisory / Consultancy: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: PharmaMar; Advisory / Consultancy: GlaxoSmithKline. S. Lheureux: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): TESARO, Inc.; Research grant / Funding (institution): Roche/Genentech; Research grant / Funding (institution): Regeneron. K. Hasegawa: Honoraria (self), Research grant / Funding (self): Daiichi-Sankyo; Honoraria (self): Chugai; Honoraria (self), Advisory / Consultancy: Merck Sharpe & Dohme Corp.; Honoraria (self): AstraZeneca; Research grant / Funding (self): Yakult Honsha; Research grant / Funding (self): Pfizer. C-H. Lai: Research grant / Funding (self): Roche; Research grant / Funding (self): TTY Biopharm. A. Gonzalez-Martinez: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy: Clovis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Merck Sharpe & Dohme Corp.; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): TESARO, Inc.; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pharmama. Q. Liu: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. S.M. Keefe: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. M. Puglisi: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. All other authors have declared no conflicts of interest.

Background Mirvetuximab soravtansine (MIRV) is an ADC comprising a FRα-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent. FORWARD I, a phase III study, evaluated the safety and efficacy of MIRV compared to chemotherapy in pts with PROC. Methods Pts with PROC, 1-3 prior lines of therapy, and FRα positivity by immunohistochemistry (stratified by predefined medium or high expression) were enrolled. Pts were randomized 2:1 to MIRV (6 mg/kg, adjusted ideal body weight) once every 21 days or investigators’ choice chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary endpoint was progression-free survival (PFS) by blinded independent review committee, in both the intention-to-treat (ITT) population (medium and high FRα expression) and, separately, in pts with high FRα. Secondary endpoints included objective response rate (ORR) and overall survival (OS). Median follow-up time was 12.5 months. Results Of 366 pts randomized, 248 received MIRV and 118 chemotherapy. Baseline characteristics were well balanced across arms. In the ITT population, the PFS hazard ratio (HR) was 0.981 (median PFS of 4.1 vs 4.4 months for MIRV and chemotherapy, respectively). For the high FRα pt subset (n = 218), additional outcomes favored MIRV over chemotherapy: PFS HR of 0.693 (4.8 vs 3.3 months; p = 0.049, not significant by Hochberg procedure), ORR (24% vs 10%), and interim OS (83/213 events (34%); median not reached vs 11.8 months; HR, 0.618). The most common adverse events (AEs) observed with MIRV were nausea (54%), diarrhea (44%), and blurred vision (43%). Fewer high grade (≥ 3) events, dose modifications, and discontinuations due to AEs were seen with MIRV. Conclusions While the study did not meet the primary endpoint, promising and consistent efficacy measures were observed in the predefined subset of high FRα PROC pts treated with MIRV. Along with favorable tolerability and differentiated safety, these findings suggest a favorable benefit-risk profile for MIRV in this biomarker-defined and difficult-to-treat population. Clinical trial identification NCT02631876. Legal entity responsible for the study ImmunoGen, Inc. Funding ImmunoGen, Inc. Disclosure K.N. Moore: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Clovis; Advisory / Consultancy: ImmunoGen; Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy: Tesaro; Advisory / Consultancy: VBL Therapeutics; Advisory / Consultancy: Aravive. A. Oaknin: Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: PharmaMar; Advisory / Consultancy, Travel / Accommodation / Expenses: Clovis; Advisory / Consultancy, Travel / Accommodation / Expenses: Tesaro; Advisory / Consultancy: ImmunoGen. D. Lorusso: Advisory / Consultancy, Research grant / Funding (institution): Tesaro; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Clovis; Advisory / Consultancy: Merrimack. C.G. Murphy: Advisory / Consultancy: Janssen; Advisory / Consultancy: Roche; Advisory / Consultancy: Nordic Pharma; Travel / Accommodation / Expenses: Ipsen; Travel / Accommodation / Expenses: Pfizer. J.A. Konner: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Clovis; Advisory / Consultancy: ImmunoGen. M. Prasad Hayes: Research grant / Funding (institution): AstraZeneca. S.K. Kim: Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: AbbVie; Advisory / Consultancy: Cytomx; Advisory / Consultancy: ImmunoGen; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy, Travel / Accommodation / Expenses: Astellas/Agensys. J. Wang: Full / Part-time employment: ImmunoGen Inc. P. Pautier: Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Clovis; Advisory / Consultancy, Travel / Accommodation / Expenses: Tesaro. M.J. Birrer: Advisory / Consultancy: Tesaro; Advisory / Consultancy: Clovis; Advisory / Consultancy: Merck Sharp & Dome; Advisory / Consultancy: Genentech USA; Advisory / Consultancy: AstraZeneca. All other authors have declared no conflicts of interest.

Background NACT is increasingly used as a model to explore new targeted therapy in combination with CT in AOC. Whether an intermediate endpoint could be used as surrogate of PFS and/or OS in pts treated with NACT remains currently elusive and was explored retrospectively in the CHIVA trial. Methods Patients (pts) with FIGO stage IIIC-IV AOC considered as unresectable after laparoscopic (Lap) evaluation were treated with 3 to 4 cycles of platinum-taxane NACT + oral nintedanib before interval debulking surgery (IDS). CT (up to 6 cycles in total) and nintedanib were pursued post-operatively. Were measured response rates at the end of NACT according to RECIST (ORR) with CT-scan and to GCIG with CA125, initial Peritoneal Cancer Index (PCI) and its evolution at IDS, complete surgical resection rate (CC0), pathologic complete or near complete response rate (pCR). These covariates in univariate analysis were included together with other prognostic clinical covariates:age, FIGO stage, ECOG, tumor size, ascitis, neutrophil/lymphocyte ratio, platelet and hemoglobin counts and symptoms (pain). Results A total of 163/188 pts included in the CHIVA trial were evaluable for the analysis. Median follow-up is 42. 6 mos (95% CI: 39.9-44.8). In the univariate Cox model, ECOG, ascitis, neutrophil/lymphocyte ratio, PCI at baseline, RECIST ORR, CC0 at IDS, pCR and treatment arm were correlated (p Conclusions Results from the CHIVA trial suggest that the rate of patients who achieve both a RECIST response to NACT and a complete surgical resection (CC0) at IDS could be used as the main primary endpoint for future NACT trials. Clinical trial identification 2011-006288-23. Legal entity responsible for the study ARCAGY-GINECO. Funding Boehringer Ingelheim. Disclosure F. Lecuru: Advisory / Consultancy, Board: AstraZeneca; Advisory / Consultancy, Proctoring: Intuitive Surgical. E. Pujade-Lauraine: Honoraria (self), Self: AstraZeneca; Honoraria (self), Self: Tesaro; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Roche; Advisory / Consultancy: Clovis; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Genmab; Advisory / Consultancy: Incyte; Advisory / Consultancy: MSD; Advisory / Consultancy: Pfizer; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Tesaro; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Tesaro. N. Raban: Travel / Accommodation / Expenses: Roche. P. Pautier: Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Clovis; Advisory / Consultancy: Genentech; Research grant / Funding (institution): PharmaMar; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Tesaro. J. Alexandre: Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Ipsen; Honoraria (self): Novartis; Honoraria (self): PharmaMar; Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Novartis; Research grant / Funding (institution): Janssen; Travel / Accommodation / Expenses: Janssen; Travel / Accommodation / Expenses: Novartis. N. Dohollou: Research grant / Funding (institution): Roche; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Lilly. A. Floquet: Advisory / Consultancy: Tesaro; Advisory / Consultancy: Clovis; Advisory / Consultancy: AstraZeneca; Travel / Accommodation / Expenses: Tesaro; 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. A. Lortholary: Honoraria (self): AstraZeneca; Honoraria (self): Tesaro. G. Ferron: Honoraria (self): Olympus Europe; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Tesaro; Travel / Accommodation / Expenses: Roche. All other authors have declared no conflicts of interest.

Chemotherapy is fundamental in the management of epithelial ovarian carcinomas both for early and advanced stages (rarely surgical treatment alone) and in almost every step of the disease. The reference schema combines carboplatin and paclitaxel intravenously. Intraperitoneal chemotherapy also proved its efficacy after complete surgery for advanced disease and should be reserved to trained teams due to its technical constraints and toxicity issues. Modalities of treatment in relapsed and progressive disease depend mainly on the free interval between this diagnosis and the last dose of platinum. Bevacizumab has proven its effectiveness in prolonging progression-free survival in 1st line setting in association with chemotherapy followed by maintenance and in case of relapse or progression both fore platinum sensitive or resistant disease. Finally, a better understanding of ovarian cancer biology will allow us to consider new molecular-targeted agents guided by the specific characteristics of each patient and each tumor.

Objectives To assess the efficacy and morbidity of cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) for relapsed ovarian granulosa cell tumors (OGCT). Study design Between 2007 and 2009, patients with relapsed OGCT who had been treated with HIPEC after CRS in our institution were retrospectively analyzed. Results We identified 7 patients who had undergone CRS plus HIPEC. Macroscopically complete cytoreduction had been performed in all patients. The location of the recurrence was exclusively the pelvis in 2 cases and both the pelvis and abdomen in 5 cases. We had administered an intraperitoneal perfusion of oxaliplatin (460mg/m 2 ) or oxaliplatin (360mg/m 2 ) plus irinotecan (360mg/m 2 ) heated up to 41–43°C for 30min. No post-operative mortality nor any grade IV morbidity (according to the Clavien and Dindo classification) had occurred. One lymphocyst (grade III) had appeared which had twice required percutaneous drainage. Six patients had experienced extra-abdominal complications (all grade II). Median follow-up after CRS plus HIPEC was 32 months (range, 25–56). Among the 7 patients, 2 are disease free, 3 had relapsed with peritoneal carcinomatosis and 2 had relapsed with liver metastases. Conclusions HIPEC (using oxaliplatin or oxaliplatin plus irinotecan) should not be recommended to treat relapsed OGCT.