Search

10016 Background: Recently, a wait and see (W&S) approach has been proposed for patients affected by desmoid tumor (DT). Specific CTNNB1 mutation has been correlated with higher risk of recurrence after surgical resection. Aim of this study was to evaluate the correlation between CTNNB1 mutation type and time to progression in patients primarily observed (TTP). Methods: We included all consecutive patients:(1) primarily observed at the Fondazione IRCSS Istituto Nazionale Tumori (Milano, Italy) or Institut Gustave Roussy (Paris, France) for primary sporadic DTs (2) with available FFPE preserved tissue for CTNNB1 mutational analysis, (3) with measurable disease and adequate follow-up. TTP from date of diagnosis to date of radiological (PRO-R) or symptomatic (PRO-S) progression were conducted by Kaplan-Meier method and log-rank test to compare strata. Results: A total of 79 patients (August 2002- July 2011) were included (81% female, 19% male); median age was 34 (IQ, 10-77); sites distribution: abdominal/chest wall (75%), extremity (21%), intra-abdominal (4%). CTNNB1 mutations were observed in 76% of DT samples: 41A (48%), 45F (25%), 45P (2%); 24% were WT. Median follow-up was 19 mo (IQ, 11-28). Thirty-six patients experienced progression (86% PRO-R, 14% PRO-S): 41A (47%), 45F (55%), 45P (100%), WT (26%). An inferior TTP at 36 months was observed in mutated patients vs WT, while no difference was detected for specific subtype mutated patients (WT 68%, 45F 24%, 41/45P 35%, p= 0.045). A variety of different treatments including surgery, hormonal therapy, chemotherapy, antiCOX2 or persistent W&S approach were proposed at progression. Forty-two patients did not receive any treatment. Conclusions: A clear trend towards a lower risk of progression was observed in WT patients, but no difference between specific mutated patients (45F vs 41/45P) was observed. Prospective studies to eventually clarify the potential role of CTNNB1 as prognostic tool in tailoring desmoids treatment are presently underway.

10092 Background: Factors predicting progression free survival (PFS) and overall survival (OS) of patients (pts) with advanced GIST treated with 400 mg daily dose IM included in the BFR14 study with a median follow up of 54 months (CI95%:47-61) was investigated evaluating added prognostic factors. Methods: 434 pts were included in this prospective multicenter trial from June 2002 to July 2009. After 1, 3 and 5 yrs of IM 400mg/day, pts free from progression were randomly offered to continue or interrupt (I arm) IM. Prognostic factors for overall survival were investigated in the entire cohort (randomized and not randomized pts) included in the BFR14. Survival was defined from the date of inclusion to the date of death for OS or to the first occurrence of disease progression under imatinib or death for PFS. A multivariate cox model including statistical significant baseline characteristics tested in univariate were included in a backward procedure d to identify independent prognostic factors for PFS then OS. Results: As of January 2012, there were 285 progressions (65%) and 161 deaths (37%). The median PFS of the entire cohort was 29 months (CI95%: 24-33) and the 4 and 5-yrs PFS were 31% and 24% respectively. A low tumour volume at inclusion, PS (0), sex (female), CD34 positivity on tumor cells were the four independent prognostic factors of a higher PFS. The 5-yrs OS was 54% (CI95%: 48-60). A higher OS was independently predicted by gender (female), PS (0), platelets count (

509 Background: With an incidence of 30%-40%, BM are common complications of HER2+ MBC. Their therapeutic management remains a challenge. As responses on central nervous system (CNS) localization have been reported with L+C combination after WBR, we sought to evaluate the clinical interest of this combination as 1st line treatment for BM in HER2+ MBC patients (pts) with the aim to avoid or to delay WBR. Methods: Eligible pts had HER2+ MBC with BM not previously treated with WBR, C or L. Pts received L1250 mg/day and C2000 mg/m2/day, days 1-14, every 21 days. The primary endpoint was a centrally assessed CNS objective response (CNS-OR) defined as a ≥50% volumetric reduction of CNS lesions in the absence of increasing steroid use, progressive neurologic symptoms, or progressive extra-CNS disease. Using a Simon’s optimal two-stage design with a minimum interesting CNS-OR rate of 20%, 41 evaluable patients were needed. Secondary endpoints included: time to progression (TTP) for both CNS and extra CNS disease;...

10062 Background: To determine the best timing for the early assessment of a functional parameter calculated with DCE-US in order to select rapidly poor responders from good responders. Methods: Al...

e12505 Background: High grade gliomas are tumors with a poor prognosis. Bevacizumab (Bvz) is commonly employed for treatment of recurrence and is currently being evaluated as first line therapy. Bv...

e20508 Background: Sarcomas of the iliopsoas compartment exhibit high local recurrence rates because it is one of the most inaccessible areas. Methods: We analyzed all iliopsoas soft tissue sarcoma...

1096 Background: Synchronous distant metastases (SDM) at diagnosis of breast cancer account for 5% of cases in ancient series. It is unclear what the recent prevalence of this condition is and whet...

10065 Background: Conventional doxorubicin-containing chemotherapy regimen may be at risk in elderly STS pts. We assessed the feasibility of treating these pts with metronomic CPM, an attractive re...

10068 Background: In previous studies, quality of margins after resection of primary STS of extremity was only defined by their size. Methods: We analyzed all patients (pts) with primary limbs STS ...

10030 Background: T is effective in advanced soft tissue sarcomas, with special regard to liposarcoma and leiomyosarcoma. Mechanisms of action may be multifold: induction of DNA damage, involving s...

635 Background: Fine-needle aspiration cytology (FNAC) has been used extensively in the diagnosis of breast lesions, but false-negative rates are a matter of concern. However, immediate onsite evaluation of breast lesions, combining FNAC results with clinical and radiological data allows to improve its diagnostic accuracy. The objective of this study was to evaluate the concordance between cytopathological and histological results in a large series of FNAC performed during the first 3-yr period of the dedicated one-stop clinic set up in our institution since 2004. Methods: We reviewed data of all patients (pts) seen in the one stop clinic between May 2004 and March 2007 who had a lesion diagnosed by FNAC and verified by histology. For benign lesions, histological verification of the lesion was mandatory each time there was no perfect concordance between clinico-radiologic features and FNAC results (such as benign FNAC but BI-RAD 5). Pts characteristics, radiological findings, cytopathological and histological (by per-cutaneous biopsy or surgery) results were extracted from the hospital computerized prospectively registered medical records. Results: A total of 1053 nodular breast lesions (mean size: 24±23 mm, BI-RAD ACR 1/2/3/4/5: 2/10/68/283/684) in 1015 pts (mean age: 59±13 years) were studied. FNAC was US-guided in 521 lesions (49.4%). FNAC classified lesions as malignant in 741 (70.4%), benign in 127 (12.0%), suspicious in 143 (13.6%), and unsatisfactory in 42 (4.0%) cases. Among definitive benign or malignant diagnosis, FNAC and histological results showed concordance in 840/868 (96.7%) cases (738 malignant and 102 benign cases). The numbers of false-negative and false-positive lesions were respectively 25/127 (19%) and 3/741 (0.4%). Among the 143 suspicious and 42 unsatisfactory specimens, 114 and 20 were malignant, respectively. Conclusions: FNAC performed in a one-stop clinic allows obtaining an immediate on-site diagnosis of breast cancer with a good concordance with histological results and low rate of unsatisfactory specimens. However, affirming benign lesion requires a multi-disciplinary team: whenever clinico-radiologic features and FNAC results are non concordant, histologic assessment is mandatory. No significant financial relationships to disclose.

10501 Background: Fibromatosis, a rare soft-tissue and locally invasive neoplasm, consist of distinct clinical entities including sporadic extra-abdominal fibromatosis (EAF). The potential morbidity of loco-regional treatments combined with the high local recurrence rate have led investigators to assess the possibility to design a “wait and see” policy in a subset of patients (pts). Up to date, molecular biomarkers of local recurrence of EAF remain unknown. As dysregulation of β-catenin (βC) expression hallmarks fibromatosis, herein we searched for βC mutations in a large retrospective European multi-centric tumors series to relate with clinicopathologic parameters. Methods: From 1987 to 2007, 155 pts with fibromatosis from all sites were gathered by the Conticanet Network were analysed. Direct sequencing of exon 3 βC gene was performed for 155 frozen tissues. All mutated cases were confirmed by an independent analysis. From this cohort, 101 pts with EAF surgically treated with curative intent and follow-up allowed us to relate βC mutational status to disease outcome. Results: Mutations of βC were detected in 84% of all cases. Among 101 pts with EAF surgically treated, similar mutations types and rates (87%) were observed, namely T41A (39.5%), S45P (9%), S45F (36.5%) and deletion (2%). There were 36 men and 65 women. Majority of pts were treated for primary EAF (57%). Most of surgical margin were RO (38%) or R1 (34%). Few pts were treated after surgery with radiation therapy (18%) and medical treatment (8%). With a median follow-up of 62 months, 51 pts (51%) relapsed. Neither clinicopathologic parameters were found to be significantly associated with βC mutational status. The five-year recurrence free-survival was significantly worse in βC mutated tumors regardless of a specific genotype, than in wild-type tumors (49 versus 93%, respectively, p=0.02). No significant difference was observed in considering either T41A, or S45F or S45P mutants, even if 45Fmutation appears to show a weak trend of significance for a dismal outcome. Conclusions: A high frequency (87%) of βC mutation hallmarks EAF from a large multicentric retrospective study. Moreover, wild type βC appears as a good prognosis marker that can be useful for therapeutic management of the EAF. [Table: see text]

10507 Background: Masitinib mesylate (AB1010, AB Science, Paris, France) is a novel protein tyrosine kinase inhibitor which, in vitro, has greater activity and selectivity than imatinib mesylate against bith wild-type c-Kit receptor and its mutated form in the juxtamembrane region. Masatinib also inhibits PDGFR and FGFR3. This multicenter phase II study evaluated the efficacy and safety of masatinib as a first-line treatment of advanced GIST. Methods: Imatinib-naïve patients with inoperable, locally advanced or metastatic GIST received oral masatinib (7.5 mg/kg/day) until progression, refusal or toxicity. A Simon “minimax two stage” design was used. Efficacy variables included response rate at two months, best response according to RECIST, disease control rate (DCR), metabolic response rate and progression free survival (PFS). Results: 30 patients with a median age of 58 years (60% of males) were included from June 2005 to April 2007 in five French institutions. The most frequent relevant grade 3 toxicities were rash (10%), neutropenia (7%) and abdominal pain (7%). One patient presented a grade 4 skin exfoliation. Three patients discontinued treatment due to suspected toxicity. At two months, the response rate was 20% (6/30 patients) according to RECIST (DCR of 98.7%, 29/30 patients) and 84.6% (11/13 evaluable patients) according to FDG-PET response criteria. After a median follow-up of 23.7 months, there were 6.7% of CR, 43.3% of PR, 46.7% of SD and 3.3% of PD as best response (DCR of 96.7%). Mean time to response was 5.7 months (0.8 to 23.3 months). The median PFS was 27.2 months with PFS rates of 68.8% at 1 year and 60.2% at 2 years. Up to date, all but one patient are alive (one patient died of post-surgical complications, unrelated to treatment). Mutational analyses of the patients’tumors are ongoing. Conclusions: The results observed with masatinib compare favorably with those reported with imatinib in front-line treatment of advanced GIST both in term of safety and efficacy and support the initiation of a phase III randomized clinical trial. [Table: see text]

This bibliographic review evaluated phase II clinical trials aimed at the identification of antitumor activity of single agents in soft tissue sarcoma (STS) after failure of standard- of-care therapy including anthracyclines and ifosfamide. A total of 63 articles (on anthracyclines, ifosfamide, trabectedin and 27 investigational agents) were included (data from 1979 to 2008).Trabectedin is the most extensively studied agent in patients with STS after failure of anthracyclines and ifosfamide (457 patients), followed by ifosfamide (412), cisplatin (144), temozolomide (137), docetaxel (114), gemcitabine (112), etoposide (95) and doxorubicin (59). Dacarbazine and the remaining investigational agents have usually been tested in 50 or fewer patients, with vastly negative results not warranting further investigation. Methodological limitations are identified in the majority of the reviewed phase II studies, including small sample size, single-institution studies, lack of independent review of the antitumor responses and inadequate description of previous therapies/agents. However, all trabectedin studies fulfilled these methodological characteristics relevant for a phase II trial. A phase II randomized trial confirmed the results of 3 prior nonrandomized studies and, therefore, trabectedin is currently considered an important new option to control advanced sarcomas in patients with STS following failure of all conventional treatments.

10584 Background: High Top2A protein expression seems to be a relevant early predictive marker for good histologic response (GHR) and better PFS in patients (pts) with LASTS treated with doxorubici...

22074 Background: Recent studies have suggested substantial differences between primary tumours and metastases for EGFR expression in colorectal cancer (CCR). Few data are available for other biolo...

10518 Background: Primary EAF is a rare disease with different clinical entities. The potential morbidity of surgery and radiotherapy and the high local recurrence have led investigators to assess ...

10590 Background: ILP with TNF-α and melphalan allows an overall response rate of 78% (complete response 31%, partial response 47%, no change 9%, and progression 13%) on locally advanced STS of the...

10075 Background: Myxoid/round cell liposarcoma (MLPS) is an uncommon soft tissue sarcoma with a relatively favorable prognosis and is considered a low grade malignancy. Methods: Retrospective analysis of 123 localized MLPS adult patients (pts) treated at our institution from 1987 to 2005 was performed. Paraffin embedded tissue was analyzed for IL6, IL6 receptor, NFkB and bcl-2 protein expression (positive (+) or negative) by tissue microarray immunostaining. Results: The median age of the 77 males and 46 females was 42 years (yr) (range 15–70). Lower extremity (LE) was the site more affected (77 pts). Median tumor size was 11 cm (range 2.5–40 cm), 87 were deep tumors and 63 were grade 1 tumors. Preoperative biopsy was carried on 38 pts. All but 2 pts underwent surgery (R0 24%, R1/R2 76%); 44 pts had a second surgery. Chemotherapy (CT) and radiation therapy were given to 30% and 52% of pts respectively. Complete remission was achieved in 98% of pts. After a median follow up of 6 yr (range 0.1–19 yr) 53 pts relapsed (43%); 37 locally, 11 distant and 5 both. Metastases occurred in 26 pts, 17 solitary and 9 multiple. The 5-yr, 10-yr and 15-yr DFS were 56%, 48% and 44% respectively. Median time to first relapse was 6.5 yr (range 0.1–16 yr). The 5-yr, 10-yr and 15-yr OS are 90%, 79% and 64% respectively. Tumor site, pre-surgical biopsy, R0 surgery and second surgery correlates with a better DFS in the multivariate analysis. So far 19 tumors have been studied for, NFkB (+) 57%, IL6 (+) 47% and Bcl2 (+) 30%, positivity. All tumors (+) for IL6 were also (+) for IL6 receptor. None of the proteins correlated to DFS and/or OS. Conclusions: Pts with localized resected MLPS require a prolonged follow-up since relapses occur after 10 yrs. PFS and OS correlate with an optimal loco-regional treatment. Half of MLPS expressed IL6, probably involving an autocrine phenomenon; whether this cytokine is involved in tumor aggressiveness, remains to be established. No significant financial relationships to disclose.

10053 Background: IM is the first-line treatment for advanced GIST and must be given continuously until disease progression or intolerance. The median progression free survival (PFS) of pts included in consecutive prospective trials is around 2 years. Pt characteristics and the exact mutational status of GIST who benefit the most from IM in term of prolonged response to IM and prolonged PFS are unknown. Methods: two hundred and seventy six pts were included in 2 consecutive prospective trials since 2001 in 2 centers. Pts receiving IM for at least 3 yrs (3 to 5 yrs) who have no exhibited any kind of progression and receiving IM continuously until december 2006 have been retrospectively analyzed both clinically and biologically. KIT and PDGFR mutations were analyzed using DHPLC and direct sequencing of frequently mutated exons (KIT 9, 11, 13, 14, 17, PDGFR 12, 14, 18). Results: after a median follow-up of 4 yrs (3–5yrs), 31 pts are free of progression and received IM continuously. The characteristics of these long term survivors favorable cohort of pts are as following: man (61%), small bowel origin (60%), liver involvement (80%), synchronous metastasis at inclusion (58%), and normal initial hemoglobin level (92%>10 g/dl). As of now, 15 pts are evaluable for mutational analysis. All but one (exon 9) pts had an exon 11 mutation. The most commun genetic alteration was an in frame deletion between 550 to 558. Conclusions: Pts with metastatic GIST arising from small bowel harboring an exon 11 mutation in the vicinity of codon 557–558 may be a very favorable subgroup. No significant financial relationships to disclose.

10074 Background: The impact of histological response (± 95% of necrosis) on patients (pts) outcome with LASTS treated by induction chemotherapy (CT) is still debated. Methods: From 1995 to 2005, 79 LASTS pts received induction CT consisting in two cycles of API-AI regimen and results were already reported (Gomez-Abuin, ASCO 2004). ERCC1, HER2 and Topoisomerase IIa (TopoII) was assessed by IHC on initial biopsies after paraffin embedding and correlated to histological response and pts outcome. Results: The median age of the 43 males and 36 females was 43 years (yr) (range 18–68) and the median tumor size at diagnosis was 109 mm (range 10–250 mm). CR was achieved in 4 pts, PR in 25 pts, SD in 45 pts and PD in 5 pts. R0 surgery was possible in 82% of pts; histological necrosis (HN) after chemotherapy was >95% in 25 pts, between 50–95% in 28 pts and 70%) after induction chemotherapy treatment is predictive for a better EFS. TopoII expression seems to be a relevant early predictive marker for outcome of pts with LASTS treated with doxorubicine-containing induction CT. No significant financial relationships to disclose.

4571 Background: Indications for radiotherapy (RT) and chemotherapy (CT) in stage II seminoma are debated. From 1982 to 2001, the policy at Institut Gustave Roussy was to treat patients (pts) with stage IIA-IIB disease with external RT (35 Gy) targeting the retroperitoneal lymph nodes (+ the mediastinum and supra-clavicular area until 1992) and pts with IIB-IIC disease with cisplatin-based CT. In stage IIB, 3 cm was the typical larger tumor size selected for RT. Methods: We retrospectively reviewed 59 consecutive pts with stage II seminoma who were treated in our institution according to this policy. Results: Median age was 40 years (range: 23–61). Pts had stage IIA (n= 9), stage IIB (n=26), and stage IIC (n=24) disease. Among the 30 pts who received RT, 8, 20, and 2 had stage IIA, IIB, and IIC disease, respectively. Among the 29 patients who received CT, 0, 7, and 22 had stage IIA, IIB, and IIC disease, respectively. They received EP (n=20), BEP (n=3), HOP (n=3), PVB (n=2), and VAB-6 (n=1). With a median...

10568 Background: N, a tumor-targeted antivascular agent, displays a biphasic dose response curve with activity shown at low dose (LD) or high dose (HD). Vascular effects involve at LD an early vessel stabilization that enhances intratumor D uptake followed by late vessel damage and at HD a rapid vessel disruption. Methods: STS patients (pts), stratified by prior D dose (> vs ≤ 300 mg/m2), were randomized to N alone given at LD (0.8 μg/m2) in arm A and at HD (45 μg/m2/d1/q1w) in B, or combined with D (60 mg/m2/d1/q3w/6 cycles) at LD in arm C and at HD in D. Primary aim of this 4-arm phase II trial was progression free survival (PFS) with CT scans performed q6w until progressive disease (PD). Using 2-stage design, each regimen was rejected if ≤ 2/14 and ≤ 7/24 pts were PD free at 3 months after 1st and 2nd stage, respectively (β=20%, α=10%, n=96). Secondary aims: adverse events (AEs), response rate by RECIST criteria and early metabolic response (MR), as quantified by fractional change in SUV using FDG-PET according to EORTC criteria Results: 66 pts have been enrolled and 55 were included in 1st study stage analysis: median age: 57 yrs; male: 30; PS ≥ 1: 26; leiomyosarcomas: 12; median prior lines: 3 (range, 0-7). In all, 488 weekly cycles were given (mean, 9; range, 1-45). Main grade 3/4 AEs were: neutropenia 18%, chills 7%. After first study stage, primary endpoint was met only in arm C (LD N + D), with 7/14 pts PD free at 3 months. Median PFS was 1.3 months (95% CI, 1.1-1.5) for arm A, 1.5 (1.1-1.8) for B, 4.5 (3.6-5.4) for C and 1.3 (1.1-1.5) for D (p=.01 for trend). By RECIST, there were no objective responses and 20/48 (42%) evaluable pts had stable disease (SD), including 1/12 in arm A, 6/12 in B, 9/12 in C and 4/12 in D. Median SD duration in arm C was 5.5 months (95% CI, 3.7-7.3). By FDG-PET imaging done after 3 weeks, 7/30 (23%) assessable pts had partial MR (4 SD/3 PD per RECIST), with mean change in SUV of -34% (SD, ± 12), while 18 pts (60%) had stable MR (7 SD/11 PD per RECIST), with mean change in SUV of 2% (± 11). Median PFS was 4.2 months in pts who achieved partial MR and 1.5 months in pts who did not (HR=0.67). Complete follow-up for arm C and central histology/radiology review are under way. Conclusions: LD NGR-hTNF plus D is safe, with promising activity as measured by FDG-PET. Clinical trial information: NCT00484341.

10007 Background: Masitinib is an oral tyrosine kinase inhibitor with greater in vitro activity and selectivity than imatinib against wild-type and juxtamembrane mutations of KIT (Dubreuil, 2009, PLoSONE). This trial studied efficacy and safety of masitinib at 12 mg/kg/day and sunitinib at 50 mg/day for the treatment of imatinib-resistant GIST. Methods: Patients with inoperable, locally advanced or metastatic GIST and showing disease progression while treated with imatinib 400 mg/day received either masitinib or sunitinib until progression. Primary endpoint was PFS evaluated with RECIST with OS as a secondary endpoint. Based upon an 80% power to detect with a Fleming design a median PFS ≥3 months (alpha 10%, unilateral), a population of 44 patients (22 per arm) was required. Stratification was applied based on mutation status. Results: 44 patients (exon 11 [66%], exon 9 [11%], wild-type or other [5%], not done at baseline [18%]) were randomized into masitinib (n=23) or sunitinib (n=21) treatment-arms from 9 centers between 02/2009 and 09/2011. After a median follow-up of 14 months, median PFS was 3.9 months (95%CI [2.6;8.1]) for masitinib vs 3.8 months [1.9;11] for sunitinib. Of those patients progressing under masitinib, 88% received sunitinib in third line. Median OS was not reached (NR) (95%CI [21;NR]) for masitinib vs 15 months [9.4;22] for sunitinib. The 18-month and 24-month OS rates for masitinib vs sunitinib were 79% (95%CI [53;92]) vs 20% [1.5;55], and 53% (95%CI [9.5;84]) vs 0%, respectively. Similar results were seen in the exon 11 subpopulation with median OS for masitinib NR (95%CI [NR;NR]) vs 15 months [9.6;22] for sunitinib. The safety profile of masitinib was better than sunitinib with a lower occurrence of severe related adverse events (AEs) (17% vs 52%) and related AEs leading to discontinuation (0% vs 9.5%). In masitinib treated patients, nausea, diarrhea and asthenia were the most common related AEs. Conclusions: Although PFS curves looked similar, this study apparently showed a longer survival in the masitinib treatment-arm with a better safety profile than sunitinib. Masitinib may potentially offer patients a new active compound for advanced GIST in the second-line setting.

10054 Background: We previously demonstrated that imatinib mesylate (IM) must not be interrupted after 1, 3 and 5 years in responding patients (pts). The impact of treatment interruption on the emergence of resistance to IM or on overall survival (OS) can not be established in this study. However, the tumor volume of residual lesions at the time of IM interruption and at the time of the best response when IM was reintroduced could influence the long term OS. Methods: This prospective multicenter BFR14 study was initiated in June 2002 and closed for inclusion in July 2009. Seventy one non progressing patients were randomized in the interruption arm (I arm) after 1 (32 pts), 3 (25 pts) and 5 years (14 pts) of IM 400 mg/day. IM was reintroduced in case of progressive disease (PD) (same dose). Tumor volume at the time of randomization, at relapse and after IM rechallenge (best response) were analyzed and compared. Results: As of January 2011, 54/71 patients restarted IM, 51 at PD and 3 without documented PD. ...

10556 Background: IM must not be interrupted after one year (yr) in responding patients (pts) (JCO 2007). The impact of IM re-introduction at progression (PD) remains unknown on the duration of GIS...

10504 Background: RE is a multikinase inhibitor that has demonstrated activity in gastrointestinal stromal tumors. We investigated its activity and safety in anthracycline pretreated metastatic sof...

10089 Background: Masitinib is a tyrosine kinase inhibitor that in vitro has greater activity and selectivity than imatinib against KIT. This multicenter, open label, phase 2 study evaluated efficacy and safety of masitinib as a first-line treatment of advanced GIST. Initial results with a median follow-up of 34 months, were previously reported in EJC 2010. We present here 5-year follow-up data from the same series with updated safety and survival data. Methods: Imatinib-naïve patients (pts) with inoperable, advanced GIST received oral masitinib (7.5 mg/kg/day) until progression, refusal or toxicity. Results: Thirty pts with a median age of 58 years (60% of males) were included from 06/2005 to 04/2007 in 5 institutions. At the cut-off date of 13/09/2011, 7/30 pts (23%) were still under treatment with median follow-up of 65 months and the median overall survival (OS) had not yet been reached (NR). The 5-year OS rate was 61.5% (95% CI [41.1;76.6]) (see Table). Among patients with confirmed KIT exon 11 mutation, 8/9 pts (89%) were still alive with one pt having died from non-treatment related causes (surgical complication) following a complete response while receiving masitinib. No additional progressions have been reported giving a total of 14 events (13 progressions and 1 death). Updated median PFS was 41.3 months (95% CI [17.5;53.8]).No additional grade 3/4 adverse events have been reported. Conclusions: Long term results of masitinib confirm an interesting activity with prolonged PFS and OS. The median PFS rate in masitinib compares very favorably to that of imatinib, which is reported as 18 months (JCO 26:626, 2008). The 5-year OS rates for masitinib in the overall and exon 11 populations also compare favorably to imatinib, both of which are reported at ≤50% for imatinib (JCO 26:626, 2008; JCO 28:1247, 2010). These results support the head to head comparison with imatinib in the currently ongoing phase 3 randomized clinical trial in first line advanced GIST pts. [Table: see text]

10044 Background: Synovial sarcoma (SS) is one of the most chemo-sensitive histological subtypes of sarcoma but with a dismal prognosis. In metastatic setting, Anthracyclin/ifosfamide-containing chemotherapy (CT) regimen is the gold standard of treatment in front-line therapy. Patients (pts) with resistant diseases are candidates to investigational drugs or higher dose ifosfamide regimen in selected pts. Methods: Pts treated in our institution, with histological confirmation of advanced SS, adequate organ function and in good condition (PS≤2) were included in this retrospective analysis. Pts who progressed after 1–2 chemotherapy lines received High-dose ifosfamide (HDI) in the form of 4 g/m2 daily (over 24 hours CI) for 3 days for a total dose of 12 g/m2; cycles were given with growth factor support and were repeated every 3 weeks. The primary endpoints were PFS and overall response rate (ORR); the secondary endpoints OS and toxicity profile. AE were assessed by NCI-CTC v. 3.0. Results: 34 pts (21 males) with a median age of 39 years (range 19-66) received this HDI regimen. PS was 0-1 in 90%. 95% of pts received prior doxorubicin, ifosfamide or both, 7 patients had 2 prior lines. Grade III monophasic pattern was seen in 21 patients, grade II in 13. 171 cycles were delivered, median number of cycles was 4 (2-10). The objective responses were CR 0; PR 15; SD 14; PD 2; and NE 3, resulting in an ORR of 44%. The clinical benefit rate was 85%. Median PFS: 11.6 months (95% CI: 9-14). Eleven pts were amenable to a subsequent resection of residual disease. Common adverse events included grade III/IV neutropenia: 47%, febrile neutropenia: 12%, thrombocytopenia: 12%, cystitis: 3%, neurologic: 3%. There was no treatment related death. Conclusions: HDI demonstrated clinically meaningful efficacy with manageable toxicity in pts who failed previous standard Ifosfamide dose. Ifosfamide remains the most active agents in SS and high dose regimen have to be considered in pts previously treated with ifosfamide.

10095 Background: We previously demonstrated that interruption of imatinib (IM) after 1, 3, and 5 yrs in responding patients (pts) with advanced GIST is associated with rapid relapse but reintroduction of IM allowed tumor control in almost all pts. Here, we examined the outcome of patients randomized in the interruption arm (I arm), and notably the characteristics of those not yet progressing. Methods: This prospective multicenter BFR14 study was initiated in June 2002 and closed for inclusion in July 2009. Seventy-one non-progressing patients were randomized in the I arm after 1 (N=32), 3 (N=25) and 5 years (N=14) of IM 400 mg/day. IM (same dose) was reintroduced in case of progressive disease (PD). Results: The median follow-up (FU) from randomization was 74, 48 and 22 months for pts randomized at 1, 3 and 5 yrs of IM treatment respectively. Updated survival data (January 2012) are summarized in the table. Out of the 3 pts not progressing in the I arm at 1 yr, 1 pt had refused to stop IM and 1 pt had a localized GIST with small residual disease at inclusion. Out of the 3 pts not progressing in the I arm at 3 yrs, 1 pt had refused to stop IM and 2 pts were included after complete resection of both primary tumor and metastases with a small residual disease. The FU of pts randomized at 5 yrs was short but out of the 5 non progressive pts, 2 are considered in PD on functional imaging (January 2012), 2 had a locally advanced GIST subsequently operated during IM and before randomization, and 1 had no target lesion at inclusion (resection of synchronous metastases). Conclusions: All but one pts with residual masses under IM and randomized in the I arm have relapsed. Six out of 7 patients not yet progressing in the I arm had reached complete remission following surgery at inclusion or before randomization (initial resection/debulking of metastases). [Table: see text]

Background The objective of this study is to explore the off-label use of targeted therapies (TTs) for patients with osteosarcoma registered within the French Sarcoma Group – Bone Tumor Study Group (GSF-GETO) national registry. Methods All patients with an osteosarcoma, registered between January 1, 2009 and July 15, 2013 were analyzed. Results Twenty-nine patients with refractory relapsed osteosarcomas received 33 treatment lines of TTs. The median age at the beginning of treatment was 19 years (range 9–72). The median number of previous lines of chemotherapy was 3 (range 1–8). Before inclusion, 3 patients were in second complete remission, 26 were in progression for metastatic relapse. Twenty-three patients received sirolimus (in combination with cyclophosphamide for 18); 5, sunitinib; 4, sorafenib; and one, pazopanib. Stable disease was observed for 45.5 % of patients (95 % Confidence Interval (CI) [20–52.8]). The median Progression-Free Survival (PFS) was 3 months (95 % CI [2–5.4]) for patients treated by sirolimus and 1.8 months (95 % CI [1.3–2.8]) for patients receiving multi-targeted tyrosine kinase inhibitors; 6-month PFS 15 %. The median Overall Survival (OS) was 6.8 months (95 % CI [4.7–12.1]), and one-year OS was 24 %. In a multivariate analysis, PFS was superior for patients receiving sirolimus compared to other TTs (Hazard Ratio (HR) = 2.7, 95 % CI [1.05–7.1]). No toxic death was reported. Grade 3 and 4 toxicities were observed in 27 and 6 % of cases respectively. Conclusion Off-label TTs, especially sirolimus, reported benefit in the treatment of refractory osteosarcomas with an acceptable toxicity profile, including in pediatric population.

LBA9006 Background: We developed a web-application for an early detection of symptomatic relapse, complications and early supportive care in high-risk lung cancer patients between visits. A dynamical analysis of the weekly self-reported symptoms automatically triggered physician visit. Methods: We performed a national multi-institutional phase 3 prospective randomized study to compare web-application follow-up (experimental arm) for which patient’s self-scored symptoms that were weekly sent (between planned visits) to the oncologist and a clinical routine assessment with a CT-scan (every 3-6 months or at investigator’s discretion - standard arm). High risk lung cancer patients without progression and with a 0-2 performance status (PS) after an initial treatment were included. Maintenance chemotherapy or TKI therapy were allowed. In the experimental arm, an email alert was sent to the oncologist when some predefined clinical criteria were fulfilled: an imaging was then quickly prescribed. Early supportive cares were provided if adequate. The primary endpoint was to detect an improvement of 12% in 9 months survival in favor of the experimental arm (α = 5%, β = 20%, unilateral test). The boundary for declaring superiority with respect to overall survival at the pre-planned interim analysis was a p-value of less than 0.006. The PS at relapse, the quality of life (QOL) and cost-effectiveness were also investigated. Results: 121 patients were included in the intent-to-test survival analysis (90% were stage III/IV, median age: 65 y): 60 (61) in the experimental (standard) arms with equivalent baseline characteristics. Median follow-up was 9 months. Median overall survival in months was 19 (11.8), p=0.0014 (n = 121; HR = 0.33; 95 % CI, 0.16-0.67) and the PS at the first relapse was 0-1 for 81.5% (35.3%) of the patients (p