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Background: Around 15% of adult GIST are wild type for KIT/PDGFRA mutations (KPWT), usually have SDH deficiencies, and are resistant to imatinib (IM). The underlying mechanisms include overexpression of HIF1α in SDH deficient-GIST, high IGFR signaling through MAPK, BRAF mutation or STAT3 activation. Regorafenib (RE), targeting these pathways, could be more active as upfront therapy in KPWT GIST. Methods: Patients (pts) >18, with advanced non pretreated KPWT GIST were eligible after central confirmation by next-generation sequencing (NGS). Eligible pts received RE at 160mg/d for 21/28d cycles. Primary end-point was disease control rate (DCR) at 12 weeks (RECIST 1.1 ) by central radiological assessment (CRA). Secondary objectives were PFS, OS, ORR (RECIST,Choi), safety and QoL. An amendment allowed previous IM (adjuvant). Statistical assumptions [H0 73% and H1 90% (α 0.1 and β 0.2)], defined a sample size of 20 pts. Results: From May 2016 to October 2020, 30pts with KPWT GIST (by Sanger) underwent central molecular screening. Among the 15 non-eligible pts, 8 harbored KIT exon 11 mutations, 3 exon 9 and 3 PDGFRA exon 18 by NGS. The remaining 16 (53.3%) molecularly eligible pts were enrolled and started RE except one pt due to COVID-19 pandemic. The trial was prematurely closed due to low recruitment, especially after COVID outbreak. Demographics and treatment details in the table. Based on CRA, 12w-DCR was 86.7%. With a median (m) FU of 26 (5-44) months (mo), 10/15 pts progressed, with a mPFS of 10.8 mo (95% CI 6.9-14.8). 6 mo, 9 mo and 12 mo PFS rates were 65%, 48% and 29% respectively. 2 pts were PD-free at 25 and 43 mo from start of RE. 6/15 pts died, with a mOS of 33.5 mo (95% CI NR). [Formula presented] Conclusions: The study results approach the prespecified activity threshold. The low recruitment rate could have affected this attainment. Other analysis of secondary endpoints are ongoing. The high percentage of overlooked mutant GIST by Sanger raises the need of NGS in presumed KPWT GIST. Clinical trial identification: NCT02638766. Legal entity responsible for the study: Spanish Group for Research on Sarcoma (GEIS). Funding: Bayer. Disclosure: J. Martin Broto: Financial Interests, Personal, Expert Testimony, Honoraria: Lilly;Financial Interests, Personal, Expert Testimony, Honoraria: PharmaMar;Financial Interests, Personal, Expert Testimony, Honoraria: Eisai;Financial Interests, Personal, Expert Testimony, Honoraria: Bayer;Financial Interests, Personal, Invited Speaker: PharmaMar;Financial Interests, Institutional, Invited Speaker: PharmaMar;Financial Interests, Institutional, Invited Speaker: Eisai;Financial Interests, Institutional, Invited Speaker: Novartis;Financial Interests, Institutional, Invited Speaker: IMMIX Biopharma;Financial Interests, Institutional, Invited Speaker: Lixte;Financial Interests, Institutional, Invited Speaker: Karyopharm;Financial Interests, Institutional, Invited Speaker: Bayer;Financial Interests, Institutional, Invited Speaker: Celgene;Financial Interests, Institutional, Invited Speaker: Pfizer;Financial Interests, Institutional, Invited Speaker: BMS;Financial Interests, Institutional, Invited Speaker: Blueprint;Financial Interests, Institutional, Invited Speaker: Deciphera;Financial Interests, Institutional, Invited Speaker: Nektar;Financial Interests, Institutional, Invited Speaker: FORMA;Financial Interests, Institutional, Invited Speaker: Amgen;Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo;Financial Interests, Institutional, Invited Speaker: Lilly;Financial Interests, Institutional, Invited Speaker: AROG;Financial Interests, Institutional, Invited Speaker: Adaptimmune;Financial Interests, Institutional, Invited Speaker: GSK. N. Hindi: Financial Interests, Personal, Invited Speaker: PharmaMar;Financial Interests, Personal, Advisory Board: PharmaMar;Financial Interests, Institutional, Research Grant: PharmaMar;Financial Interests, Institutional, Sponsor/Funding: PharmaMar;Financial Interests, Institutional, Research Grant: Nova tis;Financial Interests, Institutional, Research Grant: Eisai;Financial Interests, Institutional, Research Grant: Immix Bio;Financial Interests, Institutional, Sponsor/Funding: Bayer;Financial Interests, Institutional, Sponsor/Funding: Deciphera;Financial Interests, Institutional, Sponsor/Funding: Daychii;Financial Interests, Institutional, Sponsor/Funding: Blueprint;Financial Interests, Institutional, Sponsor/Funding: Adaptimmune;Financial Interests, Institutional, Sponsor/Funding: GSK;Financial Interests, Institutional, Sponsor/Funding: Karyopharm;Financial Interests, Institutional, Sponsor/Funding: Celgene;Financial Interests, Institutional, Sponsor/Funding: AROG. J. Lavernia: Financial Interests, Personal, Invited Speaker: PharmaMar;Financial Interests, Personal, Invited Speaker: BMS. C. Serrano: Financial Interests, Personal, Invited Speaker: Bayer;Financial Interests, Institutional, Research Grant: Bayer. D. Moura: Financial Interests, Institutional, Research Grant: Novartis;Financial Interests, Institutional, Research Grant: Eisai;Financial Interests, Institutional, Research Grant: PharmaMar;Financial Interests, Institutional, Research Grant: Immix Bio. J. Blay: Financial Interests, Institutional, Research Grant: Bayer;Financial Interests, Personal, Invited Speaker: Bayer;Financial Interests, Institutional, Research Grant: Novartis;Financial Interests, Personal, Invited Speaker: Novartis;Financial Interests, Institutional, Research Grant: Roche;Financial Interests, Personal, Invited Speaker: Roche;Financial Interests, Institutional, Research Grant: Deciphera;Financial Interests, Personal, Research Grant: Deciphera. E.R. Fumagalli: Financial Interests, Institutional, Research Grant: Bayer. All other authors have declared no conflicts of interest.

International audience; Soft tissue sarcomas are a group of rare and aggressive connective tissue neoplasms for which curative therapeutic opportunities are limited in advanced phase. Clinical trials assessing immunotherapy in these tumors have so far reported limited efficacy. The objective of this study is to provide a description of the immunologic landscape of sarcomas to guide the next clinical trials of immunotherapy in these diseases. The gene expression profile of 93 immune checkpoint (ICP) and membrane markers (MM) of immune cells was analyzed in a series of 253 soft tissue sarcoma (synovial sarcoma, myxoid liposarcoma, sarcoma with complex genomic and GIST) using Agilent Whole Human Genome Microarrays. The unsupervised hierarchical clustering of gene expression level was found able to properly group patients according to the histological subgroup of sarcoma, indicating that each sarcoma subgroup is associated with a specific immune signature defined by its gene expression pattern. Using the prognostic impact of CIBERSORT signature on metastatic-free survival in each subgroup, specific target could be proposed for each of the four groups: Treg through ICOS and GITR in GIST, M0 macrophages in all four sarcoma subtypes, OX40 in SS, CD40 in GIST and SS. The immune landscape of sarcoma was found to be as heterogeneous as the histotypes and molecular subtypes, but strongly correlated to the histotype. Histotype adapted immunotherapeutic approaches in each sarcoma subtypes must be considered in view of these results, consistently with the already reported specific response of histotypes of ICPs.

Survival of adolescents and young adults (AYA) with sarcoma is lower than in younger patients. The objective of this study was to describe the regional healthcare circuits, the differences in the management between adult, paediatric and mixed units and to assess the prognostic impact of compliance with clinical practice guidelines (CPGs) on overall survival (OS) and on relapse free survival (RFS).Retrospective analysis of the management and long term follow-up of all 13-25 year old patients with a sarcoma diagnosed in the Rhône-Alpes area between 2000 and 2005.140 patients satisfied inclusion criteria and were selected. The majority of 13-25 year old patients were treated in paediatric units. Joint management resulted in a higher rate of discussion in multidisciplinary tumour board, inclusion in clinical trials, and fertility preservation. Non-compliance with guidelines was observed in 65% of cases. Overall compliance was not reported to correlate to survival. Compliance of radiotherapy with CPG's seemed associated with a better prognosis for OS (HR = 0.20, 95% CI = [0.10-0.40]; p 0.0001) and RFS (HR = 0.18, 95% CI = [0.09-0.37; p 0.0001) as well as compliance of surgery for OS (HR = 0.43, 95% CI = [0.23-0.81]; p = 0.01). Multivariate Cox regression analysis revealed other independent predictors of OS like age at diagnosis, stage and histological subtype.Management of AYA in joint units seems to improve the quality of care. Compliance of surgery and radiotherapy with CGP's seems to improve survival.

Purpose There are some lines of evidence suggesting a potential role of immunotherapy for treating patients with osteosarcomas. Patients and methods This was an open-label, multicentre, phase 2 study of pembrolizumab in combination with metronomic cyclophosphamide in patients with advanced osteosarcomas. All patients received 50 mg b.i.d. of cyclophosphamide one week on and one week off and 200 mg of intravenous pembrolizumab (every 3 weeks). There was a dual primary end-point, encompassing both the non-progression and objective responses at 6 months per Response Evaluation Criteria in Solid Tumours (RECIST), version 1.1. An objective response rate of 20% and/or a 6-month non-progression rate of 60% were determined as reasonable objectives for treatment with meaningful effect. Correlative studies of immune biomarkers were planned from the patients' tumour samples. Results Between October 13 2015 and July 3 2017, 17 patients were included. Fifty were assessable for the efficacy end-point. Four patients experienced tumour shrinkage, resulting in a partial response (PR) in one patient (6.7%). The 6-month non-progression rate was 13.3% (95% confidence interval [CI]: 1.7–40.5). The most frequent adverse events were grade I or II nausea, anaemia, anorexia and fatigue. programmed death-ligand 1 (PD-L1) expression rate was low, observed in only 2 cases of 14 with available tumour material. The only patient who experienced PR had a PD-L1–negative tumour. Conclusion Programmed cell death 1 (PD-1) inhibition has limited activity in osteosarcomas. Further studies investigating PD-1 inhibitor in combination with agents modulating the microenvironment are warranted. Trial registration This study is registered with ClinicalTrials.gov, number NCT02406781 .

BRAF mutations occurring in 1%-5% of patients with non-small-cell lung cancer (NSCLC) are therapeutic targets for these cancers but the impact of the exact mutation on clinical activity is unclear. The French National Cancer Institute (INCA) launched the AcSé vemurafenib trial to assess the efficacy and safety of vemurafenib in cancers with various BRAF mutations. We herein report the results of the NSCLC cohort.Tumour samples were screened for BRAF mutations in INCA-certified molecular genetic centres. Patients with BRAF-mutated tumours progressing after ≥1 line of treatment were proposed vemurafenib 960 mg twice daily. Between October 2014 and July 2018, 118 patients were enrolled in the NSCLC cohort. The primary outcome was the objective response rate (ORR) assessed every 8 weeks (RECIST v1.1). A sequential Bayesian approach was planned with an inefficacy bound of 10% for ORR. If no early stopping occurred, the treatment was of interest if the estimated ORR was ≥30% with a 90% probability. Secondary outcomes were tolerance, response duration, progression-free survival (PFS), and overall survival (OS).Of the 118 patients enrolled, 101 presented with a BRAFRoutine biomarker screening of NSCLC should include BRAFClinicalTrials.gov identifier: NCT02304809.

Despite being associated with a very poor prognosis, long-term survivors across all series of Desmoplastic Small Round Cell Tumor (DSRCT) have been reported.To analyze patients 'characteristics associated with a prolonged survival after DSRCT diagnosis.All consecutive patients treated for DSRCT in nine French expert centers between 1991 and 2018 were retrospectively analyzed. Patients with a follow-up of less than 2 years were excluded and cure defined as being disease-free at least 5 years.100 pts were identified (median age 25 years, 89% male). 27 had distant metastases at diagnosis and 80 pts underwent upfront chemotherapy (CT). 71 pts were operated, 20 pts without prior CT). Surgery was macroscopically complete (CC0/1) in 50 pts. Hyperthermic intraperitoneal Chemotherapy (HIPEC) was administered during surgery in 15 pts 54 pts had postoperative CT and 26 pts had postoperative whole abdomino-pelvic RT (WAP-RT). After a median follow-up of 103 months (range 23-311), the median overall survival (OS) was 25 months. The 1- year, 3-year and 5-year OS rates were 90%, 35% and 4% respectively. 5 patients were considered cured after a median disease-free interval of 100 months (range 22-139). Predictive factors of cure were female sex (HR = 0.49, p = 0.014), median PCI12 (HR = 0.32, p = 0.0004), MD Anderson stage I (HR = 0.25, p 0.0001), CC0/1 (HR = 0.34, p 0.0001), and WAP-RT (HR = 0.36, p = 0.00013). HIPEC did not statistically improve survival.Cure in DSRCT is possible in 5% of patients and is best achieved combining systemic chemotherapy, complete cytoreductive surgery and WAP-RT. Despite aggressive treatment, recurrence is common and targeted therapies are urgently needed.

Item does not contain fulltext Background: Solitary fibrous tumors (SFT) are rare unusual ubiquitous soft tissue tumors that are presumed to be of fibroblastic differentiation. At present, the challenge is to establish accurate prognostic factors. Patients and methods: A total of 214 consecutive patients with SFT diagnosed in 24 participating cancer centers were entered into the European database (www.conticabase.org) to perform univariate and multivariate analysis for overall survival (OS), local recurrence incidence (LRI) and metastatic recurrence incidence (MRI) by taking competing risks into account. A prognostic model was constructed for LRI and MRI. Internal and external validations of the prognostic models were carried out. An individual risk calculator was carried out to quantify the risk of both local and metastatic recurrence. Results: We restricted our analysis to 162 patients with local disease. Twenty patients (12.3%) were deceased at the time of analysis and the median OS was not reached. The LRI rates at 10 and 20 years were 19.2% and 38.6%, respectively. The MRI rates at 10 and 20 years were 31.4% and 49.8%, respectively. Multivariate analysis retained age and mitotic count tended to significance for predicting OS. The factors influencing LRI were viscera localization, radiotherapy and age. Mitotic count, tumor localization other than limb and age had independent values for MRI. Three prognostic groups for OS were defined based on the number of unfavorable prognostic factors and calculations were carried out to predict the risk of local and metastatic recurrence for individual patients. Conclusion: LRI and MRI rates increased between 10 and 20 years so relapses were delayed, suggesting that long-term monitoring is useful. This study also shows that different prognostic SFT sub-groups could benefit from different therapeutic strategies and that use of a survival calculator could become standard practice in SFTs to individualize treatment based on the clinical situation.

Item does not contain fulltext BACKGROUND: Uterine sarcomas are a group of mesenchymal tumours comprising several histologies. They have a high recurrence rate following surgery, modest outcome to systemic therapy, and poor overall survival. Pazopanib is a multi-targeted tyrosine kinase inhibitor approved for non-adipocytic advanced soft tissue sarcomas (STS). Here we investigated whether response to pazopanib in patients with uterine sarcomas differs from that of patients with non-uterine sarcomas. PATIENTS AND METHODS: Uterine sarcoma patients were retrieved from all soft tissue sarcoma patients treated with pazopanib in EORTC Phase II (n=10) and Phase III (PALETTE) (n=34) studies. Patient and tumour characteristics, response, progression free and overall survival data were compared. RESULTS: Forty-four patients with uterine sarcoma were treated with pazopanib. The majority of patients had uterine leiomyosarcoma (LMS) (n=39, 88.6%) with high grade tumours (n=37, 84.1%) compared to 54.8% (n=164) in the non-uterine population. The median age was 55years (range 33-79) and median follow up was 2.3years. Uterine patients were heavily pre-treated, 61.3% having >/=2 lines of chemotherapy prior to pazopanib compared to 40.8% in the non-uterine population. Five patients (11%), all LMS, had a partial response (95% CI 3.8-24.6). Median progression free survival (PFS) 3.0months (95% CI 2.5-4.7) in uterine versus 4.5 (95% CI 3.7-5.1) in non-uterine STS. Median overall survival (OS) was 17.5months (95% CI 11.1-19.6), longer than the non-uterine population, 11.1months (95% CI 10.2-12.0) (p=0.352). CONCLUSIONS: Despite heavy pre-treatment, pazopanib shows signs of activity in patients with uterine sarcoma with the similar outcomes to patients with non-uterine STS.

Les sarcomes sont des cancers rares et heterogenes, dont la prise en charge est complexe et non optimale pour la majorite des patients. Les trois elements cles de la prise en charge sont l’obtention d’un diagnostic avere, la discussion pluridisciplinaire du dossier en reunion de concertation pluridisciplinaire specialisee et la chirurgie effectuee dans une equipe entrainee. Afin d’ameliorer significativement la prise en charge des patients, trois reseaux nationaux anatomopathologiques et cliniques dedies aux sarcomes/GIST/tumeurs desmoides et constitues de centres experts regionaux ont ete structures en 2010 avec le soutien de l’Institut national du cancer et de la direction generale de l’Offre de soins: les reseaux RRePS, NetSarc et ResOs. Une base de donnees partagee a ete mise en oeuvre avec pour objectif de collecter differents indicateurs de qualite de prise en charge et de suivre leur evolution a l’echelle nationale. Apres cinq annees d’activite, les trois reseaux couvrent entre 73 et 91 % des 4 000 nouveaux patients annuels attendus. Cette organisation en reseaux de soins apporte de nombreux benefices pour les patients: elle permet de faciliter l’acces aux expertises anatomopathologiques et cliniques ainsi qu’une meilleure prise en charge initiale (imagerie, biopsie), une meilleure qualite de chirurgie et un meilleur acces aux traitements innovants. Cette organisation permet egalement de structurer la recherche, d’optimiser l’utilisation de techniques diagnostiques et la prescription de traitements couteux et de standardiser la collecte de donnees de prise en charge et de suivi a l’echelle nationale.

Background The EDIFICE surveys have been conducted since 2005 to provide a better understanding of the participation of the French population in cancer screening programs. The breast cancer (BC) screening program is nowadays widely implemented throughout the target female population: women aged 50-74 years are invited for a mammogram once every two years. We analyzed the behavior of women over time (between 2005 and 2016) regarding BC screening according to age-group, socioprofessional categories (SPC) and social vulnerability. Methods The fifth nationwide observational survey, EDIFICE 5, was conducted by phone interviews using the quota method. A representative sample of 1299 subjects aged 50-74 years with no history of cancer was interviewed between November 22 and December 7, 2016. Interviewees (women aged 50-74 yrs; N=657) were asked about their uptake of BC screening, and the date of the last examination to determine the follow-up rate. Demographic data on social characteristics and SPC were also collected to determine the level of social vulnerability (validated EPICES score). Results Compliance with BC screening (a mammogram within the past 2 years) decreased significantly from 81% in 2014 to 75% in 2016 (P=0.02). From 2014, a significant impact of age was observed (P=0.02 in 2014 and 2016). In 2016, and for the first time, a significant and disturbing decrease in follow-up rate was recorded among younger women (age 50-54 yrs: 88% in 2014 vs 74% in 2016, P=0.01). SPC had no effect on compliance with screening. However, since 2008, fluctuations have been observed among unemployed individuals (U), with a significant decline in compliance in 2016 (U: 81% in 2014 vs 73% in 2016, P=0.03). In 2016, social vulnerability was seen as a factor that negatively impacts on compliance with BC screening (P≤0.01), but not in 2011 or 2014. We also observed a significant overall decrease in 2016 among both vulnerable (76% in 2014 vs 65% in 2016; P=0.04) and non-vulnerable populations (85% in 2014 vs 79% in 2016, P=0.04), highlighting a general loss of confidence. Conclusion For the first time since 2005, compliance with BC screening dropped significantly in France in 2016. A significant overall decline was observed regardless of social vulnerability status. Disturbing significant decreases were observed among the younger age-group (women aged 50-54 yrs) of the target population of the organized program, and among unemployed women. Although organized programs have been shown to ensure equitable access to cancer screening, this achievement remains precarious and requires regular monitoring. Citation Format: Morère JF, Eisinger F, Blay J-Y, Greillier L, Brignoli-Guibaudet L, Lhomel C, Cortot AB, Couraud S, Viguier J. Decline in compliance to breast cancer screening in France: Results of the 5th EDIFICE survey [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-08-07.

Tenosynovial giant cell tumors (TGCT), are rare colony stimulating factor-1(CSF-1)-driven proliferative disorders affecting joints. Diffuse-type TGCT often causes significant morbidity due to local recurrences necessitating multiple surgeries. Imatinib mesylate (IM) blocks the CSF-1 receptor. This study investigated the long term effects of IM in TGCT. We conducted an international multi-institutional retrospective study to assess the activity of IM: data was collected anonymously from individual patients with locally advanced, recurrent or metastatic TGCT. Sixty-two patients from 12 institutions across Europe, Australia and the United States were identified. Four patients with metastatic TGCT progressed rapidly on IM and were excluded for further analyses. Seventeen of 58 evaluable patients achieved complete response (CR) or partial response (PR). One- and five-year progression-free survival rates were 71% and 48%, respectively. Thirty-eight (66%) patients discontinued IM after a median of 7 (range 1–80) months. Reported adverse events in 45 (78%) patients were among other edema (48%) and fatigue (50%), mostly grade 1–2 (89%). Five patients experienced grade 3–4 toxicities. This study confirms, with additional follow-up, the efficacy of IM in TGCT. In responding cases we confirmed prolonged IM activity on TGCT symptoms even after discontinuation, but with high rates of treatment interruption and additional treatments.

The natural history of localized high-grade sarcomas of the digestive tract (SDT) excluding GIST has been rarely considered owing to their low incidence and heterogeneity. We describe the histoclinical characteristics of SDT and correlate them with patients' outcomes.We retrospectively collected medical files from a European database covering connective tissue tumors listed in Europe for about twenty years. Only untreated localized primary high-grade SDT were included. A central histological review was performed for each case. Patients' characteristics were compared and correlated with clinical outcomes.A total of 45 patients were identified. Leiomyosarcomas (LMS) and undifferentiated sarcomas (UDS) were predominant, the former having better overall survival (OS) and progressionfree survival (PFS) while the latter having a worse outcome than the other histological types. Complete remission was obtained in 34 patients (75%) and was associated with male sex, age over 40 years and monofocal tumor. Complete surgery and LMS histology were associated with a better prognosis without any significant difference in baseline characteristics or in treatment modalities.Complete surgery and histological type seem to be prognostic indicators of SDT. These results suggest the importance of treating these patients in a reference center.

Background REGOBONE, a non-comparative phase II, double-blind, PL-controlled trial was designed to evaluate the activity of REG, an oral multikinase inhibitor, in four parallel independent bone sarcomas cohorts: osteosarcoma, Ewing sarcoma, chondrosarcoma, and chordoma. REG demonstrated promising activity in the osteosarcoma cohort (Lancet Oncol 2019). We report here the CS cohort results. Methods Eligible CS pts were randomized (2:1) to receive either REG (160 mg/d, 21/28 d) or PL with optional cross-over at the time of centrally confirmed progressive disease (PD). Key-eligibility criteria were age ≥10 years, histologically confirmed diagnosis of CS, confirmed measurable PD not amenable to curative-intent, 1-2 previous chemotherapy (CT) regimen(s) for relapsed disease, ECOG 0-1. 24 pts were planned in the REG arm based on a A’Hern’s single-stage design for phase II trials (1-sided a = 0.05, and 80% power) to detect a 25% improvement in the progression-free rate (PFR) at 12 weeks (P0=50%) as evaluated by central review per RECIST1.1. Major secondary endpoints were PFS, OS and safety. Results From September 2014 to February 2019, 46 CS pts were included. Six pts were not eligible for efficacy analysis. Of 40 efficacy-evaluable pts (16 in PL arm and 24 in REG arm); 25 were men, median age was 61 (20-75) years. 13 pts (54.2%; one-sided CI95% = [35.8-[) were non-progressive at 12 weeks in the REG arm vs. 6 (37.5%; CI95% = [17.8-[) in the PL arm. Median PFS was 19.4 (CI95% = 11.4-35) vs. 8 (CI95%= 4.3-23.4) weeks for REG and PL arms, respectively. At the time of the analysis there is not enough event to describe OS. 14 pts crossed-over to REG after PD on PL. The most common Gr3-5 REG-related AEs during the double-blind period were hypertension (12%), cutaneous toxicity (8%), asthenia (8%), diarrhea (8%), thrombocytopenia (8%), and 1 fatal liver cytolysis. Conclusions Despite a PFR at 12 weeks lower than expected, this randomized non comparative study shows a promising signal of benefit of REG in relapsed CS, with a median of PFS of 19 weeks and, an acceptable toxicity. Clinical trial identification EudraCT: 2013-003910-42, NCT02389244. Legal entity responsible for the study UNICANCER. Funding Bayer HealthCare SAS. Disclosure F. Duffaud: Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Roche; Advisory / Consultancy: Lilly; Travel / Accommodation / Expenses: Pharmamar; Travel / Accommodation / Expenses: Leo Pharma. J. Blay: Honoraria (self), Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Bayer; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): GSK. O. Mir: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Bayer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Blueprint Medicines; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Eli-Lilly; Honoraria (self), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Incyte; Honoraria (self), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Ipsen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Lundbeck; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Servier; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Vifor Pharma. P. Boudou Rouquette: Honoraria (self): BMS; Honoraria (self): Roche; Travel / Accommodation / Expenses: Pharmamar; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Novartis. All other authors have declared no conflicts of interest.

Background The capacity of inducing tumor shrinkage in advanced soft tissue sarcomas (STS) is an unmet need beyond the first-line of systemic therapy. Pivotal studies of approved drugs reported RECIST response rates below 10%. Thus, it is challenging to relieve symptoms related to tumor volume in patients progressing to anthracycline-based schemes. Besides that, the overall response rate (ORR) is an appropriate surrogate for overall survival. This phase II trial explores the combination of trabectedin (T) and concurrent radiotherapy (RT) in the metastatic setting and is supported by preclinical experiments and previous phase I trial. Methods Patients received T 1.5 mg/m2 in 24-h infusion and started RT (30 Gy, 3 Gy/day) from the end of the first T perfusion. Most relevant inclusion criteria were metastatic progressing STS, a maximum of two previous systemic lines for advanced disease with at least one previous anthracycline-based line. Neither all the lesions nor all the sites were required to be irradiated. The main endpoint was ORR by RECIST 1.1. A Simon 2-stage was used to estimate 35% ORR of interest for further investigation (α = 0.1, power 90%; P0 = 0.10). Central pathology and radiological review were mandatory. Results From 10/2017 to 11/2018, 27 patients were enrolled. Histologies were: leiomyosarcoma 7 (26%), synovial sarcoma 6 (22%), liposarcoma 4 (15%) and other 10 (37%). The median of previous lines was 2, and ECOG distribution was 0: 19 (70%) and 1: 8 (30%). With a median follow-up of 6 months (1-12), there were 9 events of progression and 3 events of death. The 6-month PFSR was 75% and the 6-month OSR was 86%. From 26 evaluable patients by RECIST, there were 15 PR (57.7%), 7 SD (26.9%) and 4 PD (15.4%). One G3 and 3 G1 pneumonitis were observed. One toxic death occurred (sepsis) being G3-4 neutropenia observed of 7 (26%) while febrile neutropenia was reported in 2 (7.4%) cases. Conclusions T concurrent with RT showed a relevant activity in progressing metastatic setting in a wide range of STS types, giving options for tumor shrinkage beyond the first-line of advanced STS. The RECIST ORR of 57.7% and 6-m PFSR of 75% confirm the synergy of T+RT. Clinical trial identification NCT02275286. Legal entity responsible for the study GEIS (Spanish Group for Research on Sarcoma). Funding GEIS, ISG (Italian Sarcoma Group), FSG (French Sarcoma Group); PharmaMar. Disclosure J. Martin Broto: Research grant / Funding (institution): EISAI; Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar; Advisory / Consultancy: Lilly. A. Italiano: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Roche; Honoraria (self), Advisory / Consultancy: Daiichi Sankyo; Advisory / Consultancy: Inmune Design; Honoraria (self), Advisory / Consultancy: Epizyme; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Bayer; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self): Novartis; Research grant / Funding (self): Merck Serono; Research grant / Funding (self): AstraZeneca/MedImmune; Research grant / Funding (self): MSD Oncology. R.M. Alvarez Alvarez: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: PharmaMar; Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Honoraria (self): Pierre Fabre; Honoraria (self): Pfizer; Honoraria (self), Research grant / Funding (institution): Novartis; Honoraria (self): Bayer; Honoraria (self): Bristol-Myers Squibb; Research grant / Funding (self): Roche; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Peregrine Pharmaceuticals; Research grant / Funding (self): AbbVie; Research grant / Funding (self): Merrimack; Research grant / Funding (institution): Janssen. A. Lopez Pousa: Travel / Accommodation / Expenses: PharmaMar. A. Redondo: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Tesaro; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar; Advisory / Consultancy: Clovis Oncology; Research grant / Funding (institution): Eisai. J. Blay: Honoraria (self), Research grant / Funding (self): PharmaMar. A. Gronchi: Honoraria (self), Advisory / Consultancy: Novartis; Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Lilly; Advisory / Consultancy, Travel / Accommodation / Expenses: Nanobiotix; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar; Honoraria (self): Pfizer. N. Hindi: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Novartis. All other authors have declared no conflicts of interest.

Background About half of ESS do not harbor a JAZF1 or YWHAE fusion and other rearrangements have already been reported. With the aim to provide a comprehensive description of the molecular landscape of endometrial stromal sarcomas (ESS), we investigated by RNA-sequencing a series of tumors diagnosed as ESS based on the morphology but negative for JAZF1 and/or YWHAE in FISH experiments. Methods This study was performed between September 2017 and December 2018 as a Centre Leon Berard monocentric retrospective translational research program on tumor samples from an investigational cohort of 43 ESS patients. For clustering analyses, we used a control cohort composed of 19 patient samples of BCOR-rearranged sarcomas (n = 8), low-grade ESS with JAZF1-SUZ12 fusion (n = 5), high-grade ESS carrying a BCOR internal tandem duplication (n = 1), uterine leiomyoma (n = 2) and uterine leiomyosarcomas (n = 3). RNA sequencing was performed from FFPE material in all cases using TruSeq RNA Access Library Prep Kit (Illumina®). Results A chromosomal rearrangement was identified in 74% of the cases (n = 32). We identified biologically homogeneous groups of tumors such as the JAZF1-fused (to PHF1 and SYNGAP1) and the BCOR-rearranged (BCOR-ITD, ZC3H7B-BCOR, CREBBP-BCOR). Using a clustering approach on transcriptomic data, tumors were divided in 3 subgroups: one mainly composed of BCOR-rearranged ESS (n = 7), one mainly composed of JAZF1-fused ESS (n = 14) and one composed of various molecular subtypes (n = 22). This 3 subgroups display significantly different survivals (Log-rank test, p = 0.004). Five cases which harbored a YWAHE-NUTM2B fusions clustered separately: 3 cases in the group of indolent tumors (JAZF1-fused ESS) and 2 cases in the group of aggressive tumors (BCOR-rearranged sarcomas). Of note, those 2 cases harbored also a single nucleotide variant, one on BCOR and one on BCORL1. Results of RNA-seq and clustering analysis have allowed a better classification in 6 cases. Conclusions This is the largest series of RNAseq performed in a very rare subtype of tumors: ESS. We report new and recurrent molecular variants of ESS including previously unreported fusions. RNA-sequencing may support the diagnosis of ESS and help a better classification. Legal entity responsible for the study The authors. Funding InterSARC grants. Disclosure All authors have declared no conflicts of interest.

Background The EDIFICE surveys have been conducted every three years since 2005. The aim of the surveys is to provide a better understanding of the participation of the French population in cancer screening programs. The breast cancer screening program is nowadays widely implemented throughout the female population aged 50-74 years; however, the question of whether it could be adapted according to breast cancer risk factors is currently under debate. This analysis focuses on awareness of the nature of breast cancer risk factors among the lay population and physicians. Methods This fourth nationwide observational survey, EDIFICE 4, was conducted by phone interviews using the quota method. A representative sample of 1602 individuals aged between 40 and 75 years old was interviewed between June 12 and July 10, 2014. A mirror survey on a representative sample of 201 general practitioners (adjusted for age and geographical area) and 100 oncologists (adjusted for type of healthcare institution and geographical area) was conducted between July 9 and August 8, 2014. Interviewees were all asked to cite five main risk factors for breast cancer. Results For lay persons (737 women with no history of cancer), the breast cancer risk factors reported were: for 54%, heredity and family history; for 29%, unhealthy lifestyle, including smoking, poor diet, stress, alcohol, physical inactivity; for 15%, exposure to exogenous hormone therapy; for 4%, air pollution; for 4%, sunburn on breasts; for 4%, late childbearing or no childbearing, and for 2%, overweight/obesity. Among physicians (70 female general practitioners and 35 female oncologists), the breast cancer risk factors reported were: for 98%, heredity and family history; for 51%, exposure to exogenous hormone therapy; for 39%, late childbearing or no childbearing; for 32%, unhealthy lifestyle, including smoking, poor diet, stress, alcohol, physical inactivity; for 22%, overweight/obesity; for 20%, age; for 22%, no breast feeding, and for 2%, air pollution. Conclusion We observed a relatively satisfactory level of understanding regarding the different risk factors for breast cancer despite the lack of indication of any qualitative ranking. Although overweight is a known risk factor for breast cancer, this fact is still not clearly understood among physicians and not widely known by the general public. On the other hand, both physicians and also half of the lay population were well aware of the fact that heredity is a risk factor for breast cancer. Citation Format: Morère J-F, Viguier J, Blay J-Y, Touboul C, Lhomel C, Eisinger F, Pivot X. Awareness of brest cancer risk factors among lay persons and physicians. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-09-14.

Item does not contain fulltext OBJECTIVE: UtS are a group of uncommon tumors representing 1% of malignant neoplasms of the female genital tract, and 7% of sarcomas. The objective of this study was to evaluate the factors associated with the clinical behavior UtS. METHODS: Information on 269 patients with advanced or metastatic first line UtS treated by chemotherapy was available in a database containing information on 3270 patients with advanced soft tissue sarcomas (STS) entered in EORTC-STBSG clinical trials between 1977 and 2010. The chemotherapy was aggregated in 4 categories: anthracyclines alone, ifosfamide alone, the combination of doxorubicin and ifosfamide, and CYVADIC. RESULTS: Among the 269 UtS pts, there were 231 deaths (median OS 10.4months, 95% CI: 9.1-11.9) and 257 progressions and/or deaths (median PFS 4.1months, 95% CI: 3.5-4.9). Multivariate analyses reported PS (p

This phase II trial shows that sorafenib warrants further clinical exploration in advanced chordoma patients., Background There is no consensual treatment of locally advanced or metastatic chordomas. Patients and methods We conducted a multicenter, open-label, uncontrolled phase II trial of sorafenib (800 mg/day). The primary end point was the 9-month progression-free rate according to RECIST 1.1. All patients had documented progressive disease at the time of study entry. Results Twenty-seven patients were enrolled between May 2011 and January 2014. The median age was 64 (range, 30–86) years. There were 17 men and 10 women. Twelve patients had been previously treated with chemotherapy and molecularly targeted agents. The maximum toxicity grade per patient was grade 3 in 21 cases (77.8%) and grade 4 in 4 cases (14.8%). Sorafenib provided an intent-to-treat best objective response of 1/27 [3.7%; 95% confidence interval (CI) 0.1% to 19.0%], a 9-month progression-free rate of 73.0% (95% CI 46.1–88.0) and a 12-month overall survival rate of 86.5% (95% CI 55.8–96.5). Survival curves were similar in pretreated and not pretreated patients. Discussion Additional clinical trials further exploring sorafenib as a treatment of locally advanced or metastatic chordomas are warranted.

Background: Alveolar soft part sarcoma (ASPS) is an orphan malignancy associated with a rearrangement of transcription factor E3 (TFE3), leading to abnormal MET gene expression. We prospectively assessed the efficacy and safety of the MET tyrosine kinase inhibitor crizotinib in patients with advanced or metastatic ASPS. / Patients and methods: Eligible patients with reference pathology-confirmed ASPS received oral crizotinib 250 mg bd. By assessing the presence or absence of a TFE3 rearrangement, patients were attributed to MET+ and MET− sub-cohorts. The primary end point was the objective response rate (ORR) according to local investigator. Secondary end points included duration of response, disease control rate (DCR), progression-free survival (PFS), progression-free rate, overall survival (OS) and safety. / Results: Among 53 consenting patients, all had a centrally confirmed ASPS and 48 were treated. A total of 45 were eligible, treated and assessable. Among 40 MET+ patients, 1 achieved a confirmed partial response (PR) that lasted 215 days and 35 had stable disease (SD) as best response (ORR: 2.5%, 95% CI 0.6% to 80.6%). Further efficacy end points in MET+ cases were DCR: 90.0% (95% CI 76.3% to 97.2%), 1-year PFS rate: 37.5% (95% CI 22.9% to 52.1%) and 1-year OS rate: 97.4% (95% CI 82.8% to 99.6%). Among 4 MET− patients, 1 achieved a PR that lasted 801 days and 3 had SD (ORR: 25.0%, 95% CI 0.6% to 80.6%) for a DCR of 100% (95% CI 39.8% to 100.0%). The 1-year PFS rate in MET− cases was 50% (95% CI 5.8% to 84.5%) and the 1-year OS rate was 75% (95% CI 12.8% to 96.1%). One patient with unknown MET status due to technical failure achieved SD but stopped treatment due to progression after 17 cycles. The most common crizotinib-related adverse events were nausea [34/48 (70.8%)], vomiting [22/48 (45.8%)], blurred vision [22/48 (45.8%)], diarrhoea (20/48 (41.7%)] and fatigue [19/48 (39.6%)]. / Conclusion: According to European Organization for Research and Treatment of Cancer (EORTC) efficacy criteria for soft tissue sarcoma, our study demonstrated that crizotinib has activity in TFE3 rearranged ASPS MET+ patients. / Clinical trial number: EORTC 90101, NCT01524926

Purpose: To evaluate whether trabectedin as first-line chemotherapy for advanced/metastatic soft tissue sarcoma prolongs progression-free survival (PFS), compared to doxorubicin and, in the phase IIb part here, to select the most appropriate trabectedin treatment schedule (3-hour or 24-hour infusion) in terms of safety, convenience and efficacy.Patients and methods: In this randomised multicentre prospective dose-selection phase IIb superiority trial, 133 patients were randomised between doxorubicin (n = 43), trabectedin (3-hour infusion, T3h) (n = 47) and trabectedin (24-hour infusion, T24h) (n = 43). PFS was defined as time from random assignment until objective progression by response evaluation criteria in solid tumours (RECIST 1.1), a global deterioration of the health status requiring discontinuation of the treatment, or death from any cause.Results: The study was terminated due to lack of superiority in both trabectedin treatment arms as compared to the doxorubicin control arm. Median PFS was 2.8 months in the T3h arm, 3.1 months in the T24h arm and 5.5 months in the doxorubicin arm. No significant improvements in PFS were observed in the trabectedin arms as compared to the doxorubicin arm (T24h versus doxorubicin: hazard ratio (HR) 1.13, 95% confidence interval (CI) 0.67-1.90, P = .675; T3h versus doxorubicin: HR 1.50, 95% CI 0.91-2.48, P = .944). Only one toxic death occurred in the T3h arm, but treatment had to be stopped due to toxicity in 7 (15.2%) (T3h), 8 (19.5%) (T24h) and 1 (2.5%) doxorubicin patients.Conclusion: Doxorubicin continues to be the standard treatment in eligible patients with advanced/metastatic soft-tissue sarcoma (STS). Trabectedin 1.5 mg/m(2)/24-hour infusion is the overall proven approach to delivering this agent in the second-line setting for patients with advanced or metastatic STS. (C) 2015 Elsevier Ltd. All rights reserved.

Background Sarcomas are rare but aggressive diseases. Specialized multidisciplinary management is not implemented for all patients in most countries. We investigated the impact of a multidisciplinary tumor board (MDTB) presentation before treatment in a nationwide study over 5 years. Patients and methods NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized MDTB, funded by the French National Cancer Institute to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB and second pathological review are mandatory for sarcoma patients in France. Patients' characteristics and follow-up are collected in a database regularly monitored and updated. The management and survival of patients presented to these MDTB before versus after initial treatment were analyzed. Results Out of the 12 528 patients aged ≥15 years, with a first diagnosis of soft tissue and visceral sarcoma obtained between 1 January 2010 and 31 December 2014, 5281 (42.2%) and 7247 (57.8%) were presented to the MDTB before and after the initiation of treatment, respectively. The former group had generally worse prognostic characteristics. Presentation to a MDTB before treatment was associated with a better compliance to clinical practice guidelines, for example, biopsy before surgery, imaging, quality of initial surgery, and less reoperations (all P

Background This phase III open-label trial investigated the efficacy of nilotinib in patients with advanced gastrointestinal stromal tumors following prior imatinib and sunitinib failure. Patients and methods Patients were randomized 2 : 1 to nilotinib 400 mg b.i.d. or best supportive care (BSC; BSC without tyrosine kinase inhibitor, BSC + imatinib, or BSC + sunitinib). Primary efficacy end point was progression-free survival (PFS) based on blinded central radiology review (CRR). Patients progressing on BSC could cross over to nilotinib. Results Two hundred and forty-eight patients enrolled. Median PFS was similar between arms (nilotinib 109 days, BSC 111 days; P = 0.56). Local investigator-based intent-to-treat (ITT) analysis showed a significantly longer median PFS with nilotinib (119 versus 70 days; P = 0.0007). A trend in longer median overall survival (OS) was noted with nilotinib (332 versus 280 days; P = 0.29). Post hoc subset analyses in patients with progression and only one prior regimen each of imatinib and sunitinib revealed a significant difference in median OS of >4 months in favor of nilotinib (405 versus 280 days; P = 0.02). Nilotinib was well tolerated. Conclusion In the ITT analysis, no significant difference in PFS was observed between treatment arms based on CRR. In the post hoc subset analyses, nilotinib provided significantly longer median OS.

Chordomas are rare, malignant bone tumors of the skull-base and axial skeleton. Until recently, there was no consensus among experts regarding appropriate clinical management of chordoma, resulting in inconsistent care and suboptimal outcomes for many patients. To address this shortcoming, the European Society of Medical Oncology (ESMO) and the Chordoma Foundation, the global chordoma patient advocacy group, convened a multi-disciplinary group of chordoma specialists to define by consensus evidence-based best practices for the optimal approach to chordoma. In January 2015, the first recommendations of this group were published, covering the management of primary and metastatic chordomas. Additional evidence and further discussion were needed to develop recommendations about the management of local-regional failures. Thus, ESMO and CF convened a second consensus group meeting in November 2015 to address the treatment of locally relapsed chordoma. This meeting involved over 60 specialists from Europe, the United States and Japan with expertise in treatment of patients with chordoma. The consensus achieved during that meeting is the subject of the present publication and complements the recommendations of the first position paper.

Synovial sarcoma is an aggressive sarcoma subtype characterized by a recurrent translocation t(X;18). We report here that the genomic complexity assessed by comparative genomic hybridization is strongly associated with outcome independently of response to neoadjuvant chemotherapy.Synovial sarcoma (SS) is an aggressive soft-tissue tumor. Despite being considered as a chemosensitive disease, the real impact of perioperative chemotherapy on metastasis-free survival (MFS) is controversial. We have shown that metastatic relapse of SS is strongly associated with genomic complexity. There are no data regarding the potential correlation between genomic complexity and response to chemotherapy.The study population included 65 SS patients diagnosed between 1991 and 2013 and with available tissue material. Genomic profiling was carried out by using array-CGH. Forty-five SS out of the 65 patients were treated with neoadjuvant anthracycline/ifosfamide-based chemotherapy. Radiological response was assessed according to RECIST criteria. Histological response was defined by the percentage of recognizable tumor cells on the surgical specimen.Genomic complexity was significantly associated with MFS. However, there was no statistically significant association between radiological or histological response and genomic complexity.The absence of significant association between response to chemotherapy and genomic complexity suggests that the prognostic value of chromosome instability in SS is independent of response to chemotherapy; mechanisms leading to metastatic relapse of SS are intrinsic to the biology of the tumor and current cytotoxic drugs are only poorly efficient to prevent it.

Background Duodenal GISTs represent 3–5% of all GISTs with limited understanding of patient outcomes. We conducted a retrospective analysis of primary localized duodenal GISTs. Methods Patients were identified via a survey from 16 FSG centers ( n = 105), and a group of 9 patients enrolled in the BFR14 trial. Data were collected from the original database and patient files, in agreement with French legislation. Results 114 patients were included, with a median age of 57. Tumors originated mainly in D2 (33%), or D3 (24%), with a median size of 5 cm. 109 patients had resection of the primary tumor; with a Local Resection (LR, n = 82), a pancreaticoduodenectomy (PD, n = 23), and data were missing for 4 patients. Resections were R0 ( n = 87, 79%), R1 ( n = 8, 7%), R2 ( n = 6). Tumor characteristics were: KIT+ ( n = 104), CD34+ ( n = 58). Miettinen risk was low ( n = 43), and high ( n = 52). Imatinib was administered preoperatively ( n = 11) and post-operatively ( n = 20). With a median follow-up of 36 months (2–250), 98 patients are alive, and 33 relapsed. The 5-year OS and EFS rates are 86.5% and 54.5%. EFS was similar for patients in the LR and the PD groups ( P > 0.05 ). In multivariate analysis, ECOG PS, and CD34 expression are independent prognostic factors on OS. Miettinen risk and spindle cell type are independent predictive factors for relapse. Conclusions Patients with resected duodenal GIST have a reasonably favorable prognosis. This study favors a preservation of pancreas when there are no anatomical constraints. LR exhibit similar survival and smaller morbidity then PD.

These findings may potentially influence future clinical practice, with encouraging long-term survival data and better safety of masitinib with respect to sunitinib indicating a positive benefit–risk ratio. Considered in the setting of effective subsequent therapies, data show that adding masitinib to the armaterium of drugs used to treat GIST generates a clinically relevant survival benefit., Background Masitinib is a highly selective tyrosine kinase inhibitor with activity against the main oncogenic drivers of gastrointestinal stromal tumor (GIST). Masitinib was evaluated in patients with advanced GIST after imatinib failure or intolerance. Patients and methods Prospective, multicenter, randomized, open-label trial. Patients with inoperable, advanced imatinib-resistant GIST were randomized (1 : 1) to receive masitinib (12 mg/kg/day) or sunitinib (50 mg/day 4-weeks-on/2-weeks-off) until progression, intolerance, or refusal. Primary efficacy analysis was noncomparative, testing whether masitinib attained a median progression-free survival (PFS) (blind centrally reviewed RECIST) threshold of >3 months according to the lower bound of the 90% unilateral confidence interval (CI). Secondary analyses on overall survival (OS) and PFS were comparative with results presented according to a two-sided 95% CI. Results Forty-four patients were randomized to receive masitinib (n = 23) or sunitinib (n = 21). Median follow-up was 14 months. Patients receiving masitinib experienced less toxicity than those receiving sunitinib, with significantly lower occurrence of severe adverse events (52% versus 91%, respectively, P = 0.008). Median PFS (central RECIST) for the noncomparative primary analysis in the masitinib treatment arm was 3.71 months (90% CI 3.65). Secondary analyses showed that median OS was significantly longer for patients receiving masitinib followed by post-progression addition of sunitinib when compared against patients treated directly with sunitinib in second-line [hazard ratio (HR) = 0.27, 95% CI 0.09–0.85, P = 0.016]. This improvement was sustainable as evidenced by 26-month follow-up OS data (HR = 0.40, 95% CI 0.16–0.96, P = 0.033); an additional 12.4 months survival advantage being reported for the masitinib treatment arm. Risk of progression while under treatment with masitinib was in the same range as for sunitinib (HR = 1.1, 95% CI 0.6–2.2, P = 0.833). Conclusions Primary efficacy analysis ensured the masitinib treatment arm could satisfy a prespecified PFS threshold. Secondary efficacy analysis showed that masitinib followed by the standard of care generated a statistically significant survival benefit over standard of care. Encouraging median OS and safety data from this well-controlled and appropriately designed randomized trial indicate a positive benefit–risk ratio. Further development of masitinib in imatinib-resistant/intolerant patients with advanced GIST is warranted.

Background Rare cancers are defined as cancers with an incidence of Methods The first part of Arcagen is a restrospective feasibility cohort of pts with sarcoma, thymic cancer, rare ovarian or head and neck cancers with previously collected tumour samples available, from any stage. Molecular analysis was performed using FoundationOne CDx for all histologies but sarcoma were FoundationOne Heme was used. Clinical data including demographic data, medical history, treatment and survival data were collected. Results Eighty-seven pts from 3 centres were screened, molecular data was successfully obtained for 75 pts which were included for the analysis (failure rate 14%). 41 pts were diagnosed with sarcoma (19 myxofibrosarcoma, 22 undifferentiated pleomorphic sarcoma), 9 with ovarian germ cell cancer, 14 with rare head and neck cancer and 11 with thymic cancer. The median age at diagnosis was 64 (range 19-85). Most pts had reportable genomic alterations (89%). The mean tumor mutational burden was low, 4.19Muts/MB (range 0-14). In the sarcoma cohort the most frequent alterations were TP53 (n = 25), ATRX (n = 8), CDKN2A/B (n = 7) and RB1 (n = 7). In the ovarian germ cell cohort, 5 pts (55%) had no reportable genomic alterations, KRAS and ARID1A mutations were found in 2 cases. In the thymic cancer cohort, HRAS, ASXL1 and BRAF mutations were found in 2 pts. In the head and neck cohort the most frequent alterations were TP53 (n = 10), ARID1A (n = 4) and ERBB2 (n = 3, 2 mutations, 1 amplification). Overall, 35 pts had druggable molecular alterations, including 4 pts for which the treatment is approved for their disease. Conclusions In our rare tumour cohort, 47% presented clinically relevant genomic alterations. Further molecular analysis of rare tumours is needed. Prospective recruitment in Arcagen is ongoing, using the EORTC SPECTA platform. We aim to recruit a total of 1000 pts with rare tumours with different histologies in order to further understand the biology of these tumours and improve pts survival. Legal entity responsible for the study EORTC. Funding Roche. Disclosure J-Y. Blay: Honoraria (self), Research grant / Funding (self): Roche-Genentech. All other authors have declared no conflicts of interest.

Background Genomic alterations of receptor tyrosine kinases (RTK) or ligands are biomarkers for some targeted therapies in a fraction of cancers, with heterogeneous responses across tumor types. A general model to predict the efficacy of a targeted treatment in a given tumor type bearing a RTK genomic alteration is lacking. Through database and literature review, we investigated whether the role of a RTK in the normal lineage could predict the response to RTK inhibitors in cancers arising from the same lineage. Methods An analysis of the literature and query of public databases on RTK function in normal cell lineages and neoplastic cells was conducted, for 16 selected RTK (EGFR, HER2, KIT, FLT3, TRKA-B-C, ROS1, ALK, RET, MET, and FGFR1-2-3-4). The physiological role of RTK in the development/maintenance of cell lineages was assessed by looking at the phenotypes resulting from the alteration of the RTK in animal models and/or known human germline mutations. The activity of TKI monotherapy in genomic-driven clinical trials was analyzed through a systematic review of published phase I-II-III studies. Efficacy was defined as a median progression-free survival > 6 months and of a response rate > 30%. A matrix was built to test the association between the physiological role and clinical activity of each RTK according to lineage contexts. Results This analysis reveals a relationship between the role in lineage development and the magnitude of clinical activity of a TKI in a cancer arising from the same lineage. For missense mutations only, the clinical activity was higher when the RTK is involved in the development or maintenance of the normal cell lineage. Conversely, in cancers harboring fusion genes and proteins involving an RTK, TKI were active regardless of cell lineage. Single agent TKI activity was consistently limited in cancers bearing RTK gene amplifications. Conclusions This analysis identifies two preferred genomic biomarkers to select candidate patient for single agent TKI, 1) fusions genes involving an RTK; 2) activating missense mutations in RTK involved in normal cell lineage physiology. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure P.A. Cassier: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche/Genentech; Honoraria (self), Research grant / Funding (institution): Blueprint; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Amgen; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck Sharp & Dohme; Research grant / Funding (institution): Tayo; Research grant / Funding (institution): Loxo; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Innate. I.L. Ray-Coquard: Honoraria (self), Research grant / Funding (self): Roche; Honoraria (self), Research grant / Funding (institution): Amgen; Honoraria (self), Research grant / Funding (institution): Genmab; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Novartis; Honoraria (self), Research grant / Funding (institution): Pfizer. D. Perol: Honoraria (self): AstraZeneca; Honoraria (self): Ipsen; Honoraria (self): Novartis; Honoraria (self): Lilly; Honoraria (self): Bristol-Myers Squibb. J-Y. Blay: Research grant / Funding (self): PharmaMar; Research grant / Funding (self): GlaxoSmithKline; Research grant / Funding (self): Novartis; Research grant / Funding (self): Eisai; Research grant / Funding (self): Lilly; Research grant / Funding (self): Merck Sharp and Dohme; Research grant / Funding (self): Bristol-Myers Squibb. All other authors have declared no conflicts of interest.