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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.

There are limited treatment options for ovarian cancer patients with early relapse after platinum chemotherapy. In preclinical studies, we previously demonstrated the promising activity of ABT-737, a Bcl-2/Bcl-xWe conducted a prospective multicenter single-arm phase II study to assess the efficacy of Navitoclax (orally available ABT-737 analogue) monotherapy in 46 heavily pretreated (2-12 lines, median = 4) patients with high-grade serous platinum-resistant ovarian tumors. Navitoclax was administered at the daily dose of 150 mg during a lead-in period (7-14 days) and then increased to 250 mg daily in the absence of dose-limiting thrombocytopenia (G3). Progression-free survival (PFS) based on RECIST v1.1 criteria was the primary endpoint. Analysis of efficacy according to the expression of Bcl-2 family proteins in tumor biopsies was also planned.The 3-month PFS was 22.7% [Navitoclax monotherapy had poor activity that was not correlated with the expression of Bim, Mcl-1 and P-ERK, without unacceptable toxicity.Clinicaltrials.gov identifier: NCT02591095.

Older patients with ovarian cancer represent a heterogeneous population. The French National Group of Investigators for the Study of Ovarian and Breast Cancer developed the geriatric vulnerability score (GVS) to identify geriatric parameters predictive of poor outcomes. A prospective validation of the GVS was needed.The EWOC-1 study (NCT02001272) was an international, open-label, phase 2, three-arm trial designed according to a two-step process. Patients aged 70 years or older with newly diagnosed stage III or IV ovarian cancer were identified and the GVS determined. Those with a GVS of 3 or greater were randomly assigned to the EWOC-1 trial, stratified by country and surgical outcome, to receive three different carboplatin with or without paclitaxel regimens; those not included in the EWOC-1 trial were followed up in the EWOC-1 registry. External validation of the GVS was a secondary endpoint of the trial. Three validation cohorts were identified: the total population (validation cohort 1 [V1], n=447), the registry-only population (validation cohort 2 [V2], n=327), and the carboplatin-paclitaxel-treated population (validation cohort 3 [V3], n=320).From Dec 11, 2013, to Nov 16, 2018, 447 patients were included in 48 academic centres in six countries; 120 in the EWOC-1 trial and 327 in the EWOC-1 registry. Median follow-up was 19·7 (95% CI 8·5-29·7) months for the total cohort; missing values were low (2%). According to the maximum likelihood analysis, the hazard ratio (HR) of death in V1 was 1·8 (95% CI 1·1-3·1, p=0·029) for those with a GVS of 1; 2·4 (1·4-4·0, p=0·0009) with a GVS of 2; 4·1 (2·5-7·0, p0·0001) for a GVS of 3; 5·5 (3·3-9·3, p0·0001) for a GVS of 4; and 9·1 (4·7-17·5, p0·0001) for a GVS of 5 compared with a score of 0. Whatever the validation cohort, GVS of 3 or more significantly segregated two groups with different overall survival: V1 (median 13·2 [95% CI: 10·8-18·7] vs 40·8 [32·0-45·6] months; HR 2·8 [95% CI 2·2-3·7]; p0·0001); V2 (11·9 [95% CI 8·8-18·1] vs 40·8 [32·0-45·6] months, HR 3·5 [2·5-4·9]; p0·0001); and V3 (18·1 [95% CI 15·8-31·8] vs 43·0 [40·6-49·7] months, HR 2·6 [1·9 to 3·7]; p0·0001).The GVS has high prognostic performance for overall survival in patients with advanced ovarian cancer, independently of geographic and historic effect (V1), as well as treatment patterns (V3), validated in an international population. Even though the GVS is time consuming it will allow the stratification of populations for clinical research and might permit the orientation of the geriatric intervention to specific domains.French National Cancer Institute.For the French translation of the abstract see Supplementary Materials section.

Introduction Cabazitaxel multiple rechallenges may be a treatment option in heavily pretreated patients with metastatic castration‐resistant prostate cancer (mCRPC) who had a good initial response to cabazitaxel and who are still fit to receive it. Our objective was to assess the efficacy and toxicity of multiple rechallenges. Patients and methods We retrospectively identified 22 mCRPC patients previously treated with docetaxel and/or androgen receptor‐targeted agents who received multiple cabazitaxel rechallenges in 9 French centers. Cabazitaxel was initiated at a dose of 25 mg/m2 q3week. A reduced dose (20 mg/m2 q3w) or an alternative schedule (mainly 16 mg/m2 q2w) was increasingly used for subsequent rechallenges. Progression‐free survival, prostate‐specific antigen (PSA) response, best clinical response, and grade ≥3 toxicities were collected. Overall survival was calculated from various time points. Results Twenty‐two patients with an initial response to cabazitaxel were rechallenged at least twice. The median number of cabazitaxel cycles was 7 at first cabazitaxel treatment, 6 at first rechallenge, and 5 at subsequent rechallenges. Median progression‐free survival at first rechallenge was 9.6 months and 5.6 months at second rechallenge. Median overall survival was 50.9 months from the first cabazitaxel dose, 114.9 months from first life‐extending therapy initiation in mCRPC, and 105 months from mCRPC diagnosis. There was no cumulative grade ≥3 neuropathy or nail disorder and one case of febrile neutropenia. Conclusion Cabazitaxel multiple rechallenges may be a treatment option without cumulative toxicity in heavily pretreated patients having a good response to first cabazitaxel use and still fit to receive it. Novelty & Impact Statements Patients with metastatic castration‐resistant prostate cancer can be treated with Cabazitaxel after docetaxel and androgen receptor‐targeted agent. This chemotherapy can be used multiple times with efficacy and manageable toxicity., We assessed the efficacy and toxicity of multiple rechallenges with cabazitaxel for 22 patients with metastatic castration‐resistant prostate cancer (mCRPC). Median overall survival was 50.9 months from the first cabazitaxel dose, 114.9 months from first life‐extending therapy initiation in mCRPC, and 105 months from mCRPC diagnosis. Cabazitaxel rechallenge may be an effective option in heavily pretreated mCRPC patients with a good initial response to cabazitaxel and still fit to receive it, without cumulative grade ≥3 toxicity.

Anti-angiogenic rechallenge with bevacizumab plus chemotherapy is effective in recurrent ovarian cancer (rOC); however, data are limited on tyrosine kinase inhibitors after progression on maintenance bevacizumab.In the randomized phase II TAPAZ trial, patients with rOC during the first year of bevacizumab maintenance therapy were assigned 2:1 to either weekly paclitaxel 65 mg/mOverall, 116 patients were randomized and treated: 79 with combination therapy and 37 with single-agent paclitaxel. Median follow-up was 13.1 months. There was no difference between treatment arms in 4-month PFS rate (61% [95% CI, 51-73%] with the combination versus 68% [95% CI, 54-85%] with paclitaxel alone), median PFS (4.9 [95% CI, 4.1-6.1] versus 5.8 [95% CI, 4.8-7.4] months, respectively) or median overall survival (13.6 versus 12.9 months, respectively). The combination was associated with more grade 3/4 toxicities (87% versus 70%, respectively) and toxicity-related paclitaxel discontinuations (22% versus 11%). Pazopanib was discontinued for toxicity in 44% of patients, most commonly for gastrointestinal and vascular events. There were two treatment-related deaths, both in the combination arm (pulmonary embolism and gastrointestinal perforation). At month 4, patient-reported outcomes deteriorated from baseline in the combination arm, particularly for abdominal/gastrointestinal symptoms, which showed a clinically important difference versus paclitaxel alone.In rOC progressing during maintenance bevacizumab, adding pazopanib to paclitaxel did not improve efficacy, increased toxicity, and compromised chemotherapy delivery.govregistration:NCT02383251.

Resume Introduction Le traitement dans le cancer de l’ovaire localement avance est une chirurgie optimale suivie d’une chimiotherapie. Les patientes avec une dissemination tumorale importante, un OMS superieur a deux et un âge superieur a 75 ans sont de mauvaises candidates pour une chirurgie premiere agressive. La chirurgie d’intervalle, apres une chimiotherapie neo adjuvante, a pour but d’obtenir davantage de chirurgies completes, d’augmenter la survie et de diminuer la morbidite liee a la chirurgie. Le critere principal de jugement etait la survie sans progression. Les criteres secondaires de jugement etaient la survie globale et la morbi-mortalite post-chirurgie. Methode Il s’agit d’une etude retrospective effectuee dans deux centres de reference francais entre janvier 2000 et decembre 2015. Les patientes qui ne pouvaient pas beneficier d’une chirurgie initiale complete etaient operees apres trois cures de chimiotherapie au centre Francois Baclesse et apres au moins cinq cures au centre Rene Gauducheau. Resultats La population analysee comportait 104 patientes, 43 (41,0 %) patientes traitees au centre Rene Gauducheau (groupe 1) et 61 (59,0 %) patientes traitees au centre Francois Baclesse (groupe 2). La survie sans progression et globale etait similaire entre les deux groupes. Elles etaient respectivement de 15,9 mois et 34 mois dans le groupe 1 vs 15,4 mois et 37,6 mois dans le groupe 2 (p = 0,72 ; p = 0,65). La duree d’hospitalisation moyenne et la morbidite postoperatoire etait similaire dans les deux groupes. Conclusion Pour des patientes fragiles, afin de limiter une chirurgie invasive, faire plus de cinq cures de chimiotherapie peut etre une option raisonnable.

BackgroundCervical cancer is the tenth diagnosed cancer in the world. Early-stage and locally recurrent disease may be cured with radical surgery or chemo-radiotherapy. However, if disease persists or recurs, options are limited and the prognosis is poor. In addition to chemotherapy, bevacizumab, an antiangiogenic agent, has recently demonstrated its efficacy in this setting. Cabozantinib is an oral small molecule tyrosine kinase inhibitor that exhibits potent inhibitory activity against several receptor tyrosine kinases that are known to influence tumor growth, metastasis, and angiogenesis. The main targets of Cabozantinib are VEGFR2, MET and AXL. It is currently approved for the treatment of metastatic renal cell carcinoma, hepatocellular carcinoma and medullary thyroid carcinoma. Given its angiogenic properties associated with growth factor receptors inhibition, Cabozantinib represents a potential active treatment in cervical carcinoma. In this context, we propose to assess the efficacy and safety of cabozantinib monotherapy in advanced/metastatic cervical carcinoma (CC) after failure to platinum-based regimen treatment.MethodsThis study is a single-arm two-stage multicenter phase II aiming to simultaneously assess efficacy and safety of Cabozantinib among advanced/metastatic cervical carcinoma (CC) after failure to platinum-based regimen treatment. The main criterion will be based on both safety and clinical efficacy by conducting a Bryant-and-Day design. Safety endpoint is the proportion of patients with clinical gastro-intestinal (GI) perforation/fistula, GI-vaginal fistula and genito-urinary (GU) fistula events grade ≥ 2 (NCI CTCAE V.5.0) occurring up to one month after the end of treatment. Efficacy endpoint is the proportion of patients with disease control rate 3 months after Cabozantinib initiation. A patients’ self-reported quality of life evaluation is also planned, as well as the investigation of nutritional outcomes. Cabozantinib will be administered at the daily dose of 60 mg given orally, without interruption until disease progression or discontinuation for any cause.DiscussionCabozantinib is a promising drug for patients with advanced/metastatic cervical cancer where few therapeutics options are available after failure to platinum-based regimen metastatic CC. It appears challenging to assess the interest of Cabozantinib in this indication, taking into account the potential toxicity of the drug.Trial registrationNCT04205799, registered “2019 12 19”.Protocol versionVersion 3.1 dated from 2020 08 31.

Importance: Single-agent carboplatin is often proposed instead of a conventional carboplatin-paclitaxel doublet in vulnerable older patients with ovarian cancer. Such an approach could have a detrimental effect on outcomes for these patients. Objective: To compare the feasibility, efficacy, and safety of single-agent carboplatin every 3 weeks, weekly carboplatin-paclitaxel, or conventional every-3-weeks carboplatin-paclitaxel in vulnerable older patients with ovarian cancer. Design, Setting, and Participants: This international, open-label, 3-arm randomized clinical trial screened 447 women 70 years and older with newly diagnosed stage III/IV ovarian cancer by determining their Geriatric Vulnerability Score; 120 patients with a Geriatric Vulnerability Score of 3 or higher were stratified by country and surgical outcome. Enrollment took place at 48 academic centers in France, Italy, Finland, Denmark, Sweden, and Canada from December 11, 2013, to April 26, 2017. Final analysis database lock April 2019. Data analysis was performed from February 1 to December 31, 2019. Interventions: Patients were randomized to receive 6 cycles of (1) carboplatin, area under the curve (AUC) 5 mg/mL·min, plus paclitaxel, 175 mg/m 2, every 3 weeks; (2) single-agent carboplatin, AUC 5 mg/mL·min or AUC 6 mg/mL·min, every 3 weeks; or (3) weekly carboplatin, AUC 2 mg/mL·min, plus paclitaxel, 60 mg/m 2, on days 1, 8, and 15 every 4 weeks. Main Outcomes and Measures: The primary outcome was treatment feasibility, defined as the ability to complete 6 chemotherapy cycles without disease progression, premature toxic effects-related treatment discontinuation, or death. Results: A total of 120 women were randomized. The mean and median age was 80 (interquartile range, 76-83; range, 70-94) years; 43 (36%) had a Geriatric Vulnerability Score of 4 and 13 (11%) had a Geriatric Vulnerability Score of 5; 40 (33%) had stage IV disease. During its third meeting, the independent data monitoring committee's recommendation led to the termination of the trial because single-agent carboplatin was associated with significantly worse survival. Six cycles were completed in 26 of 40 (65%), 19 of 40 (48%), and 24 of 40 (60%) patients in the every-3-weeks combination, single-agent carboplatin, and weekly combination groups, respectively. Treatment-related adverse events were less common with the standard every-3-weeks combination (17 of 40 [43%]) than single-agent carboplatin or weekly combination therapy (both 23 of 40 [58%]). Treatment-related deaths occurred in 4 patients (2 of 40 [5%] in each combination group). Conclusions and Relevance: This randomized clinical trial shows that compared with every-3-weeks or weekly carboplatin-paclitaxel regimens, single-agent carboplatin was less active with significantly worse survival outcomes in vulnerable older patients with ovarian cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT02001272.

International audience; BACKGROUND:Despite multimodality treatments including neurosurgery, radiotherapy and chemotherapy, glioblastoma (GBM) prognosis remains poor. GBM is classically considered as a radioresistant tumor, because of its high local recurrence rate, inside the irradiation field. The development of new radiosensitizer is crucial to improve the patient outcomes. Pre-clinical data showed that Poly (ADP-ribose) polymerase inhibitors (PARPi) could be considered as a promising class of radiosensitizer. The aim of this study is to evaluate Olaparib, a PARPi, as radiosensitizing agent, combined with the Stupp protocol, namely temozolomide (TMZ) and intensity modulated radiotherapy (IMRT) in first line treatment of partially or non-resected GBM.METHODS:The OLA-TMZ-RTE-01 study is a multicenter non-randomized phase I/IIa trial including unresectable or partially resectable GBM patients, from 18 to 70 years old. A two-step dose-escalation phase I design will first determine the recommended phase 2 dose (RP2D) of olaparib, delivered concomitantly with TMZ plus conventional irradiation for 6 weeks and as single agent for 4 weeks (radiotherapy period), and second, the RP2D of olaparib combined with adjuvant TMZ (maintenance period). Phase IIa will assess the 18-month overall survival (OS) of this combination. In both phase I and IIa separately considered, the progression-free survival, the objective response rate, the neurocognitive functions of patients, emotional disorders among caregivers, the survival without toxicity, degradation nor progression, the complications onset and the morphologic and functional MRI (magnetic resonance imaging) parameters will be also assessed as secondary objectives. Ancillary objectives will explore alteration of the DNA repair pathways on biopsy tumor, proton magnetic resonance spectroscopy parameters to differentiate tumor relapse and radionecrosis, and an expanded cognition evaluation. Up to 79 patients will be enrolled: 30 patients in the phase I and 49 patients in the phase IIa.DISCUSSION:Combining PARP inhibitors, such as olaparib, with radiotherapy and chemotherapy in GBM may improve survival outcomes, while sparing healthy tissue and preserving neurocognitive function, given the replication-dependent efficacy of olaparib, and the increased PARP expression in GBM as compared to non-neoplastic brain tissue. Ancillary studies will help to identify genetic biomarkers predictive of PARPi efficacy as radiosensitizer.TRIAL REGISTRATION:NCT03212742 , registered June, 7, 2017. Protocol version: Version 2.2 dated from 2017/08/18.

Background Brain metastases often occur in cancer evolution. They are not only responsible for death but also for disorders affecting the quality of life and the cognitive functions. Management of brain metastases usually consists in multi-modality treatments, including neurosurgery, whole brain radiotherapy (WBRT), and more recently radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT), systemic treatment (chemotherapy or targeted therapy), combined or not with corticosteroids. Almost 20% of brain metastases can present recent (within 15 days) bleeding signs on neuro-imagery. In these conditions, WBRT is the usual treatment. Yet, patients may benefit from a more aggressive strategy with SRT or FSRT. However, these options were suspected to possibly major the risk of brain haemorrhage, although no scientifically proven. Radiation oncologists therefore usually remain reluctant to deliver SRS/FSRT for bleeding brain metastases. It is therefore challenging to establish a standard of care for the treatment of bleeding brain metastases. We propose a phase II trial to simultaneously assess safety and efficacy of FSRT to manage brain metastases with hemorrhagic signal. Methods The STEREO-HBM study is a multicenter two-step non-randomised phase II trial addressing patients with at least one bleeding brain metastasis out of a maximum of 3 brain metastases. Each brain metastasis will be treated with 30 Gy in 3 fractions for 1 week. The main endpoint is based on both safety and efficacy endpoints as proposed by Bryant and Day’s design. Safety endpoint is defined as the rate of bleeding complications 4 months post-FSRT while efficacy endpoint is defined as the 6-month local control rate. Multi-modal MRI will be used to assess intra-tumoral hemorrhagic events before and after treatment. Patients’ quality of life will also be assessed. Discussion Management of bleeding brain metastases is still debated and poorly explored in clinical trials. There is sparse and weak data on the signification of pretreatment intra-tumour haemorrhagic signs or on the risk of brain bleeding complications after FSRT. We expect this first prospective phase 2 trial in this particular setting will allow to clarify the place of FSRT to optimally manage bleeding brain metastases. Trial registration NCT 03696680, registered October, 4, 2018. Protocol version Version 2.1 dated from 2018/11/09.

Background Molecular targeted therapies have improved progression-free survival (PFS) without translating systematically into overall survival (OS) for patients with metastatic renal cell carcinoma (mRCC). In this population, patient-reported outcomes (PROs) have become a significant outcome. We evaluated the methodological quality of the assessment of PROs in randomized controlled trials (RCTs) and the clinical benefit of the different treatments including survival and quality of life (QoL). Methods A systematic review identified RCTs published between January 2005 and July 2014. They were evaluated according to 11 items derived from the 2013 CONSORT PROs reporting guidelines. Survival outcomes and PROs main results were analyzed and the magnitude of clinical benefit was assessed with the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). Results 12 RCTs were included with a total of 22 publications. The mean CONSORT score for all items was 4.5 on an 11-point scale. No publication reported the power of the PROs analysis and only one reported a PRO hypothesis. 50% of studies did not interpret PROs in relation to clinical outcomes and only 18% discussed specific limitations of PROs and their implications for generalizability. By adding the QoL criterion to PFS, 4 trials (36.4%) obtained a high level of proven clinical benefit according to the ESMO-MCBS. Conclusion The methodology for assessing PROs in mRCC is not optimal. Efforts should focus on defining PROs endpoint and increasing the quality of reporting of QoL. New-generation therapies in mRCC should demonstrate a gain not only in survival but also in QoL to be included in the therapeutic arsenal.

Treatment in locally advanced ovarian cancer is optimal surgery followed by chemotherapy. Patients with significant tumor spread, OMS2, age75 years old are poor candidates for aggressive primary surgery. Interval surgery, after neo-adjuvant chemotherapy, aims to achieve more complete surgery, increase survival, and reduce surgical morbidity. The primary endpoint was progression-free survival. Secondary outcomes were overall survival and postoperative morbidity and mortality.This is a retrospective study conducted in 2 French referral centers between January 2000 and December 2015. Patients who could not benefit from a complete initial surgery were operated after 3 cures of chemotherapy at the François Baclesse center and after least 5 cures at the center René Gauducheau.The population analyzed included 104 patients, 43 (41.0%) patients treated at the René Gauducheau center (group 1) and 61 (59.0%) patients treated at the François Baclesse center (group 2). Progression-free and overall survival were similar between the 2 groups, they were, respectively, 15.9 months and 34 months in group 1 vs. 15.4 months and 37.6 months in group 2 (P=0.72; P=0.65). Mean hospital stay and postoperative morbidity were similar in both groups.For weak patients, to limit invasive surgery, doing more than 5 courses of chemotherapy may be a reasonable option.

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.

5046 Background: Darolutamide (Daro) and enzamutamide (Enza) are both next generation androgen receptor inhibitors with demonstrated activity in men with CRPC. Although both agents are associated with survival improvement, their toxicity profiles are different. To help decipher whether this may impact on patient preference, we designed the ODENZA trial. Methods: ODENZA is a prospective, randomized, open-label, multicenter, cross-over, phase II trial of preference between Daro and Enza in men with asymptomatic or mildly symptomatic metastatic CRPC. Patients were randomized 1/1 to receive Daro 1200 mg/d for 12 weeks followed by Enza 160 mg/d for 12 weeks (Daro-Enza arm) or the reverse sequence (Enza-Daro arm). In both arms, the second treatment was given in absence of evidence of cancer progression at week 12. The primary endpoint was patient preference between the two drugs, as assessed by a questionnaire at week 24. The Prescott's test was used to determine treatment preference in patients fullfilling pre planned criteria (exposure to both treatments, no progression at week 12, and completion of the preference questionnaire). A p-value greater than 0.05 indicates that there is no difference in preference between treatments. Stratification factors were performance status and prior taxane for mCSPC. After week 24, patients went on to an extension period during which they received the chosen treatment until progression or toxicity. The main secondary objectives included reasons for preference, response at week 12, cognitive assessment, and toxicity. Results: Overall 249 pts were randomized, median age 72y (68; 79), ECOG PS 0 (56%), prior taxanes (22%). Two hundred pts fulfilled the pre-planned criteria for evaluation of the preference primary endpoint : 97 (48.5% [41.3;55.7]), 80 (40.0% [33.0;47.0]), and 23 (11.5% [6.8;16.2]) chose Daro, Enza, and had no preference, respectively (unilateral p-value of 0.92). After preference assessment, 186 patients entered the extension period: 103 (55.4%) and 83 (44.6%) received Daro and Enza respectively. The most common factors influencing patient preference all numerically favored Daro over Enza, without significant differences were: less fatigue (44% vs 29%), ease of taking the medication (37% vs 31%), better quality of life (36% vs 28%), ability to be more active (26% vs 15%), ability to concentrate (22% vs 15%) and less falls (6% vs 3%). A PSA50 response was achieved in 76.2% and 83.9% at week 12 with Daro and Enza respectively (p = 0.13). Fatigue was the most frequently reported all grade adverse event at week 12, in 21% and 36% with Daro and Enza, respectively. Conclusions: More patients with early mCRPC preferred Daro over Enza, although the difference did not reach significance, with fatigue as the key influencing factor. Clinical trial information: NCT03314324.

97 Background: Cabazitaxel rechallenge could be a more efficient therapy with an acceptable toxicity than docetaxel in the treatment of patients with a metastatic castration resistant prostate cancer (mCRPC). The aim of this study was to assess the feasibility and efficacy of cabazitaxel multiple rechallenge. Methods: This is a multicenter, retrospective cohort study including patients from 9 centers in France who received 3 lines or more of cabazitaxel from February 2012 to July 2020. Cabazitaxel schedule differed between patients: 25 mg/m2 q3w, 20 mg/m2 q3w, 16 mg/m2 q2w or 10 mg/m2 weekly. Efficacy was assessed by overall survival (OS) and progression-free survival (PFS) from each cabazitaxel line start. Only toxicities grade ≥ 3 were reported. Results: Twenty-two patients were included. The median follow-up from mCRPC was 94.7 months, median age at initial diagnosis was 59.5 years old, median ISUP score at diagnosis was 4 and median PSA at diagnosis was 55 ng/ml. Median number of cabazitaxel cycles was 7 at first-line, 6 at first rechallenge, and 5 for subsequent rechallenges. Median OS from mCRPC diagnosis was 105 months. Median PFS from cabazitaxel line start was 11.8 months at first use, 9.6 for first rechallenge and 5.6 in second rechallenge (table). Only one case of febrile neutropenia and 6 events of grade ≥ 3 toxicity were reported. Conclusions: Cabazitaxel multiple rechallenge could efficiently extend OS with manageable toxicities for patients. Even if anti-PARP therapy and immunotherapy are promising treatments, cabazitaxel rechallenge could be also a relevant therapeutic option for long responder patients. Specific biomarkers should be explored to predict the efficacy of cabazitaxel rechallenge. [Table: see text]

e17595 Background: More than 20% of mCRPC present somatic DNA damage repair gene mutation (DDR). If some data are available for germline mutations, there are few studies describing the relation between somatic alterations and response to standard therapies in mCRPC. Methods: To describe outcomes of mCRPC patients treated with standard therapies according to somatic DDR status.A retrospective somatic analysis on a 69-gene panel was conducted among mCRPC patients. Progression-free survival (PFS) of first-line treatment was analyzed according to somatic DDR mutation as primary endpoint. First exposition to taxanes chemotherapy and PFS2 (time to the second event of disease progression) depending on therapeutic sequences (new-generation hormonotherapy [NGHT]/taxanes chemotherapy) were also analyzed. Results: Among 83 patients tested, 33 (40%) had a somatic DDR mutation, including 10 ATM, 5 BRCA2, 4 CHEK2, 3 CDK12, 3 FANCG, 1 BLM, 1 CHEK1, 1 FANCF, 1 FANCI, 1 FANCM, 1 MDC1, 1 MRE11A and 1 PALB2. In first-line treatment, 20 patients received taxanes and 63 NGHT. Median PFS was 9.8 months for mutated patients and 8.4 months for non-mutated patients (p = 0.9). For mutated patients, median PFS was 12.3 months in taxanes group and 9.8 months in NGHT group, (p = 0.74). One BRCA2-mutated patient treated by docetaxel was particularly long responder (PFS = 39.2 months). PFS of first exposition to taxanes was 8.2 months among mutated patients and 5.7 months among non-mutated patients (p = 0.31). Patients with BRCA1/BRCA2/ATM mutations had longer PFS compared to the others patients (10.6 months versus 5.5 months, p = 0.04). Ten patients received the chemotherapy-NGHT sequence (CHS) and 28 the NGHT-chemotherapy sequence (HCS). PFS2 were 16.5 months for mutated patients, whatever the sequence, and 11.7 months among non-mutated patients (p = 0.07). The 3 mutated patients (1 BRCA1, 1 BRCA2, 1 ATM mutation) had long PFS2 in the CHS (49.8 months). PFS2 of mutated patients in HCS was 15.6 months. Conclusions: Mutated mCRPC patients benefit from standard therapies, with long responders to taxanes among patients with BRCA1/2 and ATM mutations.

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.

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.

Background Axitinib is used after failure of first line treatment for metastatic renal cell carcinoma (mRCC). A known side effect is the increase of haemoglobin level (HbL) during treatment with a suspected correlation with better outcome. Our objective was to examine whether HbL increase during the first three months of axitinib treatment is associated with better prognosis. Methods Retrospective multicentre analysis including patients with mRCC treated with axitinib for at least three months from 2012 to 2014. Progression-free survival (PFS) was analysed by a Cox model according to gender, International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic score, high blood pressure (hBP), and maximum increase in HbL within the first three months of treatment. Results Ninety-eight patients were analysed (71% men; median age at treatment initiation: 62 years; IMDC: 24%, 50%, and 26% in the favourable, intermediate, and poor-risk group, respectively). Patients received axitinib for a median of 8 months. During the first three months, the median increase of HbL was +2.3 g/dL (−1.1; 7.2). Fifty-six (57%) patients developed hBP. In multivariate analysis, after adjustment for performance status (P

The evaluation of quality of life has become essential in gynecological oncology. Recent guidelines have been published to improve the collection, analysis and publication of the data quality of life that will make them more reliable, reproducible and integrate them into the final treatment decision. This year at ASCO, in breast cancer, the benefit of sentinel lymph node dissection compared to the quality of life has been demonstrated. New data on cognitive function in patients treated for breast cancer show the importance of the evaluation of these disorders especially among elderly patients who are at-risk populations. Medical strategies including targeted therapies can improve survival without impairing the quality of life, also with improved gastrointestinal symptoms in case of combination chemotherapy with bevacizumab in patients with ovarian cancer in a situation early recurrence. Similarly, the addition of a pathway inhibitor M- Tor (everolimus) with hormonal therapy does not induce degradation of the quality of life in women with metastatic breast cancer.

4553 Background: BISCAY is a biomarker-directed Ph1b multi-arm platform study exploring the combination of targeted therapies with anti-PD-L1, Durvalumab, in advanced urothelial cancer. Methods: Next generation sequencing (NGS) of tumour tissue samples from > 380 patients(pts) was performed using the FoundationOne assay alongside IHC for PD-L1. ct DNA from pts enrolled in trial modules at treatment initiation was profiled using the Guardant Health OMNI platform assessing a panel of 500 genes. For a subset of pts, serial plasma samples were also analysed to monitor early signs of response vs. resistance and changes in ct DNA dynamics using a bespoke NGS panel of 10 genes. Results: To date 149 pts have been actively enrolled across 7 different biomarker selected and unselected treatment modules. Across all screened pts the most prevalent genomic alterations in tumour tissue were TERT promoter (65%), TP53 (59%), KMT2D 21%, KDM6A 21%, with the most common CNV CDKN2A/ B loss (32 %). All enrolled pts tested had detectable ctDNA in plasma. Similar genomic alterations, both frequency and type, were detected in both plasma ctDNA and tumour tissue with high concordance for module specific biomarkers used for patient allocation (80% (8/10) for ATM, BRCA1 and 2). Alterations in putative biomarkers predictive of response to anti-PD-L1, such as HRR/MMR alterations and high bTMB levels ( > 20mut/Mb) were observed in22% and 40% patient plasma samples, respectively. Correlations between biomarkers across modules treatment efficacy have been explored. Conclusions: All pts with advanced bladder cancer enrolled on BISCAY who were plasma profiled had detectable ctDNA; frequencies of genomic alterations (in both tumour tissue and plasma) were comparable to prior published data sets. ctDNA may be an attractive alternative to tissue-based NGS, providing comprehensive dynamic snapshots of genomic landscapes at the start and during therapy, and warrants further prospective investigation in trials.

Introduction OLA-TMZ-RTE-01 (PHRC-K15-135, Clinicaltrial NCT03212742 ), en cours de recrutement, est un essai de Phase I/IIa dont l’objectif est de determiner la dose optimale puis l’efficacite de l’association de l’olaparib au protocole Stupp (six semaines de temozolomide et radiotherapie, suivi, apres quatre semaines de pause, de six cycles de temozolomide en traitement de maintenance), chez les patients atteints d’un gliome de haut grade non resecable. Il repose sur deux designs innovants, la « Time-to-event Continual Reassessment Method » (Tite-CRM) et le design de Case & Morgan. Nous presentons ces designs et les difficultes rencontrees par leur mise en œuvre dans l’essai. Methodes La Phase I se scinde en deux escalades de dose successives (pendant la radiotherapie puis la periode de maintenance), chacune selon une Tite-CRM [1] . Cette methode permet d’inclure les patients sans attendre un delai fixe d’observation des toxicites en leur attribuant un poids proportionnel au delai d’apparition de l’evenement, pour guider l’escalade de dose. L’efficacite, en termes de survie, de la dose d’olaparib definie lors de la Phase I sera evaluee en utilisant un design de Case & Morgan en deux etapes [2] . Ce design donne la possibilite de poursuivre l’inclusion pendant l’analyse intermediaire. Resultats Chez les patients a esperance de vie limitee, la Tite-CRM autorise une escalade de dose plus rapide qu’un design de type CRM ou 3 + 3, permettant de faire beneficier plus vite d’un traitement novateur. Les contraintes de securite liees a la dose administree restent neanmoins primordiales, que ce soit pour des toxicites a court ou a plus long terme. Le rythme d’inclusion se definit au fur et a mesure des observations en utilisant les proprietes mathematiques du design qui permettent une inclusion au jour le jour, tout en s’accordant un temps d’observation acceptable entre chaque inclusion, en partie guide par la periode definie d’observation des TDL (toxicites dose-limitantes). Mais comment definir ce rythme ? Combien de patients observer ? Et comment gerer de facon efficace le processus d’inclusion dans le cadre d’une etude multicentrique ? Telles sont les questions auxquelles nous avons ete confrontes par l’utilisation de la Tite-CRM. Les designs classiques d’essais de Phase II, tels que Simon ou Fleming, sont concus pour repondre a une problematique d’efficacite lorsque la variable d’interet est binaire, generalement la reponse au traitement, en se basant sur le fait que sa loi est binomiale. Lorsque l’efficacite est mesuree par un taux de survie, cette propriete ne tient plus. Le design de Case & Morgan repond alors a cette problematique, dans lequel le taux de survie est evalue par l’estimateur de Nelson–Aalen. Les regles de decisions sont accompagnees d’un test statistique, rendant l’utilisation et l’interpretation de ce design moins intuitives. Conclusion Au-dela des nombreux avantages que conferent les deux methodologies, elles suscitent de nombreuses questions, que ce soit des la conception de l’etude ou pendant son deroulement. Ces limites peuvent generer un frein a leur developpement, ce qui peut expliquer qu’elles soient encore peu utilisees dans les essais cliniques.

Glandular metastases (GMs) (pancreas, breast, parotid, thyroid, or contralateral adrenal) are rare in metastatic clear cell renal cell carcinoma (mccRCC). In a multicenter study we have assessed outcome from mccRCC with or without GMs.Patients with mccRCC and GM or non-GM (NGM) at first presentation of mccRCC, treated at 9 European centers (5 French, 3 UK, and 1 Belgian centers) between January 2004 and October 2013, were retrospectively analyzed. Association between overall survival (OS) and site of metastases was assessed using the log-rank test for univariate analysis and the chi-square test for multivariable Cox regression.In all, 138 patients with GM mccRCC and 420 with NGM mccRCC were included; 37.2% patients with GM had Memorial Sloan-Kettering Cancer Center (MSKCC)-favorable risk vs. 18% NGM patients; 10.7% patients with GM had MSKCC-poor risk vs. 27% NGM patients (P0.0001). Median interval from metastases to treatment was 4.2 months (range: 0-221.3mo). Median OS was 61.5 months (51.4-81.6mo) for GM and 37.4 months (31.3-42mo) for NGM (hazard ratio [HR] = 1.7; 95% CI = 1.3-2.2, P0.001). In univariate OS analysis, age, delay between initial diagnosis and metastases, MSKCC, bone/lung metastases, and GM or NGM group were significant parameters (P0.001). In multivariate analysis, adjusted according to MSKCC risk group, NGM vs. GM was a strong prognostic factor (HR = 1.4; 95% CI = 1.0-1.8, P=0.026); bone or liver metastases were also significant (HR = 1.3; 95% CI = 1.1-1.7, P0.02; HR = 1.4; 95% CI = 1.1-1.7, P0.02, respectively). Even in patients without bone or liver metastases, GM status was significant (HR = 1.8; 95% CI = 1.2-2.7, P0.004).This large retrospective study shows that the presence of at least 1 GM site in development of mccRCC was associated with a significantly longer OS. The presence of GMs vs. NGM disease was an independent prognostic factor for survival irrespective of the presence or absence of bone or liver metastases. This finding could affect daily practice in which patients with mccRCC and GMs should receive more aggressive treatment with a potential for long-term survival. The causal mechanisms for this improved prognosis in GM mccRCC would be evaluated in translational studies.

e17048 Background: Brain metastases (BM) EOC are rare and late events. We explored tumoral genetic variations of HR system. We identify genomic alterations with NGS in both primary tumor and BM EOC Methods: Seven patients suffering from histologically proven EOC and BM, which underwent neurosurgery, were included in the study. Seven matched samples (primary tumor and BM) were analyzed by high throughput sequencing after enrichment by capture of the whole exome. After bioinformatics procedures (BWA, HaplotypeCaller, Varscan2, Outlyzer) the analysis was restricted firstly to a in silico panel of 69 genes involved in HR system. Results: Mean age was 56 years (47 to 71). Five had serous and 2 endometrioid carcinomas. All the patients had an initial FIGO stage ≥IIIA, were platine-sensitive. Median time from diagnosis of EOC to BM was 29 months (24 to 76). BM occurred after first line treatment in 5 cases and after at least 2 relapses in the 2 other cases. Median Overall survival (OS) from diagnosis of BM was 17 months (1 to 45). Five primary tumor showed a variation of at least one HR gene: pathogenic variants inactivating in BRCA2 (n = 2), CDK12 (n = 1) and probably pathogenic missenses in BRIP1 (n = 1) and TOPB1 (n = 1). These 5 variations have been also found in the BM tissues. Among the 2 patients without variations in the primary tumor, 2 probably pathogenic missenses were detected in the BM tumor (1 FANCD2 and 1 FANCM). Time to BM relapse and OS were longer among these 2 last patients compared to the remaining 5 patients (median 68 vs 29 months and 90 vs 56 months, respectively). Conclusions: Patients with BM presented HR somatic mutations and are susceptible to have high response to Parp inhibitors.

4563 Background: Nivolumab (N) has been shown active in patients (pts) with mRCC after failure of 1 or 2 TKIs. Efficacy and safety of N in pts with brain metastases (BM) from RCC is still unknown. The aim of this study is to report preliminary data of the Nivoren study in pts with BM. Methods: GETUG-AFU 26 (Nivoren) is a prospective phase 2 study assessing safety and efficacy of N in a broader mRCC patient population than those recruited in the pivotal phase 3, including pts with BM (previously treated or not, but not requiring steroids), with previous mTOR inhibitor, with PS 2 as well as in previously highly pretreated pts. N was given every 2 weeks at 3mg/kg, until disease progression or unacceptable toxicity. Treatment was allowed beyond progression in case of clinical benefit. All pts had brain CT scan or MRI at baseline. Results: Up to December 2016 , 588 pts have been enrolled including 55 pts with BM (35 (67%) ,6 (12%) and 11 (21%) with 1, 2 or > 2 BM, respectively. Of those 55 pts, 10 pts (23%) were PS 2 and 25 (58%) PS 1, and 16 patients (29%) had received more that 2 lines of therapy. No previous treatment for BM was performed in 67% (n = 37), while 9% had previous brain surgery (n = 5 ;) or brain radiation (n = 17 (31%). 2/55 pts never received N. Median duration of therapy in BM pts was 2.4 months (varying from 0 to 9) with a 3-months PFS of 60% (IC95% = 45 – 73). Median OS is not reached at the time of this analysis. Among 44 pts with assessment of response on BM, 10 (23%) had objective response while 21 (48%) had local progressive disease. Neurologic deterioration requiring steroids was observed in 15 pts (32%) . Updated data will be presented at the meeting. Conclusions: This is the first large study to report preliminary safety and efficacy of N in RCC pts with BM. Safety of N in this pt population appears to be acceptable, although some pts do require steroids because of brain progressive disease. Objective response in the brain was observed in 23% of pts. Further follow up is required to determine the real benefit of N in this group of mRCC pts. Clinical trial information: NCT03013335.

The evaluation of quality of life has become essential in gynecological oncology. Recent guidelines have been published to improve the collection, analysis and publication of the data quality of life that will make them more reliable, reproducible and integrate them into the final treatment decision. This year at ASCO, in breast cancer, the benefit of sentinel lymph node dissection compared to the quality of life has been demonstrated. New data on cognitive function in patients treated for breast cancer show the importance of the evaluation of these disorders especially among elderly patients who are at-risk populations. Medical strategies including targeted therapies can improve survival without impairing the quality of life, also with improved gastrointestinal symptoms in case of combination chemotherapy with bevacizumab in patients with ovarian cancer in a situation early recurrence. Similarly, the addition of a pathway inhibitor M- Tor (everolimus) with hormonal therapy does not induce degradation of the quality of life in women with metastatic breast cancer.

580 Background: Axitinib is used after failure of first line treatment for metastatic renal cell carcinoma (mRCC). A common side effect of axitinib is the increase of hemoglobin level (HbL) during treatment with a suspected correlation with better outcome. We examined whether HbL increase during the first 3 months of axitinib treatment is associated with better prognosis. Methods: Retrospective multicenter analysis including patients with mRCC treated with axitinib for at least 3 months from 2012 to 2014 as part of the French temporary use authorization cohort. Progression-free survival (PFS) was analyzed according to the following factors: gender, International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic score at axitinib initiation, polycythemia (HbL above 16.5/18.5 g/dL or hematocrit above 56/60% for women/men), and maximum increase in HbL within the first 3 months of treatment. Results: 97 patients were analyzed (71% men; median age at diagnosis: 54.7 years [22; 80]; IMDC: 23%, 49%, and 27% in the favorable, intermediate, and poor-risk group, respectively). Patients received axitinib for a median of 8 months [3; 30]. Grade 2-3 toxicities were observed in 81% of patients. Objective response rate was 32%. The median PFS and OS were 8.9 [7.4; 9.3] and 22 [19.4; not reached] months, respectively. During the first 3 months, 81 patients (84%) experienced HbL increase with a median increase of +2.3g/dL [-1.1; 7.2] and 40 of them (51%) had an increase above this median. Eight patients (8%) presented polycythemia. In univariate analysis, significantly longer PFS was observed for men (p = 0.02), for patients who had a better IMDC prognostic score (p = 0.004), and for patients who experienced an increase of HbL ≥ 2.3 g/dL (with a median PFS of 11.7 vs. 7.4 months; p = 0.025), but not for patients with polycythemia. In a multivariate analysis, after adjustment for IMDC score (p < 0.0001) and gender (p = 0.029), an increase in HbL ≥ 2.3 g/dL was significantly associated with a longer PFS (HR = 0.57, 95%CI [0.34; 0.95]). Conclusions: HbL increase ≥ 2.3g/dL in the first 3 months of axitinib treatment was associated with longer PFS. These results require validation in a prospective trial setting.

Aim: The announcement device was an emblematic measure of the first French Plan Cancer aiming at enabling patients to have a listening and information time after diagnosis announcement and treatment proposition: the different aspects of the treatments including side effects are discussed during these specific clinics. This procedure includes a medical and paramedical consultation. Nausea and vomiting (CINV) are still one of the most common side effects of the chemotherapy (CT) despite of known risk factors and efficient supportive treatments. Hypothesizing patients with good information on CINV and preventive supportive treatments may have less CINV, our study aimed to assess the relation between the patient's satisfaction of information delivered during the diagnosis announcement procedure and the incidence of CINV after the first cycle of chemotherapy. Methods: This prospective multicentric study assessed the frequency and intensity of CINV among patients naive of CT after the first cycle of treatment, using the MASCC Antiemesis Tool (MAT). CINV were defined by≥1 emetic episode or reported nausea intensity≥3 on a 0-10 scale. Multivariate analysis was used to identify various factors related to overall CINV onset, including satisfaction defined as a satisfaction score equal or above median on a 0-10 scale for≥1 announcement consultation. Results: Data from 291 patients (women: 85.2%; mean age: 57 years) from 4 centers were analyzed. Median satisfaction score were 9 and 10 for medical/paramedical consultations (1st quartile: 8 and 9, respectively): 67% of patients were satisfied of announcement device. 40.4% of patients reported acute CINV, 34.8% delayed CINV and 52.4% overall CINV. Four independent predictive factors of CINV were found: motion sickness history (OR 2.73), highly emetogenic CT (OR 2.12), anxiety (OR 2.09) and age under 57 (OR 1.99). No relation was noted between announcement consultation satisfaction and risk of CINV. Conclusions: The announcement consultation satisfaction was not linked to lower CINV frequency. In fact, even "unsatisfied" patients gave a high score, not allowing to clearly identify the impact of satisfaction on CINV. Disclosure: All authors have declared no conflicts of interest.

Aim: Glandular metastasis (GM) as defined by pancreas, breast, parotid, thyroid and contralateral adrenal metastasis are rare in clear cell renal cell carcinoma. We have performed a multicenter comparison of metastatic clear cell RCC (mRCC) with GM and non-GM to determine if GM impacts on overall survival (OS). Methods: Data were collected from mRCC pts with GM or non-GM at metastatic presentation. GM: pts with at least one GM with or without other sites. Non-GM: pts without GM at metastatic presentation. Pts were treated in 5 French, 1 Belgian and 3 UK centers between January 2004 and October 2013. Association between OS and site of metastasis was assessed using the log-rank test for univariate analysis and the chi-square test for multivariable Cox regression. Results: 188 GM and 453 non-GM mRCC pts were analyzed. The majority were male (70.2%), median age was 59y, with no difference between the GM and non-GM groups. Interval from diagnosis to metastasis was 25.7 months (mo) (0.03-272.8)for GM and 4.8 mo (0.03-334) for non-GM (p 60y), delay between renal tumor and metastatic diagnosis, MSKCC risk group and GM or non-GM group were significant parameters in univariate OS analysis (p Conclusions: This large retrospective study shows that the presence of at least one GM at metastatic presentation of clear cell mRCC was associated with a significantly longer OS compared to non-GM pts. The presence of GM vs non-GM disease was an independent prognostic factor for OS. Further translational studies will be performed on matched primary tumor and metastasis samples to assess molecular differences between GM and non-GM. Disclosure: All authors have declared no conflicts of interest.

510 Background: Metastatic renal cell carcinoma (RCC) is still associated with a poor prognosis with an overall survival (OS) of 37 months, although some patients are long survivors despite a disseminated disease. The purpose of this study was to determine whether the presence of at least one glandular metastasis (GM), defined by metastasis in pancreas, thyroid, breast or adrenal contralateral, affect survival outcome in patients with metastatic clear cell RCC (cc-RCC). Methods: In this retrospective analysis, we included patients treated for GM and non GM (NGM) metastatic RCC at the Institut Paoli Calmettes (IPC), Marseille, France between January 2004 and May 2013. Two more centers provided data for GM cc-RCC. GM were authentified using CTscan and/or by histopathological analysis obtained at biopsy or at surgery. Patients were analyzed from the time of metastatic disease to last follow up or death. The purpose of this study was to analyze patients outcomes based on the presence or absence of GM. We analysed survival using a log rank test from the time of the diagnosis of GM to the death or last follow-up visit. Results: Among 180 patients analysed, 59 had GM. Median age 65.2 vs 61.8 years old, male 55% vs 72%, 90% vs 78% prior nephrectomy in GM and NGM group. GM sites were pancreas for 45.5%, adrenal 44.5%, thyroid: 10%, breast10%. GM was the only site of metastasis for 10% of pts. For GM group, 55.5% had histopathology proven RCC metastasis. The median follow up was 72 months and the median survival is 114 months (IC95% [62.9-NR.]) in GM group vs 33.2 months (IC95% [23-41.9]; p