Scientific <strong>Poster</strong>s – <strong>Poster</strong> <strong>Session</strong> 2intensity pattern. Objective responses at first radiologicalevaluation at 3 months were: stable disease in one pt(12.5%) and progressive disease in 7 (87.5%) pts. Treatment-relatedadverse events were G1-2 nausea/vomiting,fatigue and periorbital oedema.Conclusion: In our limited case series, imatinib showedno efficacy in the treatment of DSRCT pts unresponsive toconventional therapy, despite molecular-based selection ofpts. Probably to identify responder pts, it should be necessarya more complex evaluation of both levels of expressionand of activation of PDGFRα and β. Furthermore, enrolledpts were affected by advanced refractory disease, probablyless responsive to targeted therapies.9.5 (vs. > 9.5), platelets < 150 (vs. >150), BMI >25 (vs. 600). In univariate analysis, LDH>600 (p=0.0009) and hemoglobin < 9.5 (p=0.02) predicteda shorter survival. In multivariate analysis, only LDH >600 predicted a shorter survival. Median survival time ofpatients with LDH > 600 was 5 months (95% CI: 2.2-8.6)vs. LDH < 600 was 13.8 months (95% CI: 8.2- 19.4).Conclusion: Patients with advanced sarcomas referredto phase I studies had a median survival of 10.3 months.In this preliminary analysis, independent factors predictingshorter survival were higher LDH (>600) and lowerhemoglobin ( 500), ECOG performance status 2-3(vs. 0-1), albumin < 3.5 g/dL (vs. > 3.5g/dL), hemoglobin
Scientific <strong>Poster</strong>s – <strong>Poster</strong> <strong>Session</strong> 2sarcoma subtypes. Eight patients had molecular aberrationin the ER, 3 patients had MET mutation, 4 patients hadPTEN loss. Two patients harbored PTEN mutation andthere was 1 patient each with P13CKA and EGFR mutation.Seven patients had TP53 mutation. Interestingly nosarcoma patient tested had BRAF, KRAS, KIT mutation.All of these patients were enrolled on matched targetedphase 1 clinical trials whenever possible. Ongoing patientoutcomes will be updated and reported.Conclusion: It is feasible to identify potential druggableaberrations in a subset of patients with sarcoma. Completemolecular profiling to understand response and resistancemechanisms and increased availability of novel targetedagents are needed.<strong>Poster</strong> #171A PHASE I/II STUDY OF TEMSIROLIMUS WITHLIPOSOMAL DOXORUBICIN FOR THETREATMENT OF HIGH RISK BONE AND SOFTTISSUE SARCOMADavid Loeb; Katherine Thornton; Allen Chen; Matteo Trucco;Breelyn Wilky; Preeti Shah; Naheed Gul; Maria Carrera;Christian Meyer; Jonathan Powell<strong>Oncology</strong>, Johns Hopkins University, Baltimore, MD, USAObjective: Adjuvant chemotherapy for poor prognosisbone and soft tissue sarcoma patients has limited efficacy.One potential explanation for this failure to substantiallyimprove survival would be the presence of inherently chemoresistantsarcoma stem cells, whose persistence wouldlead to relapse, metastasis, and death. Our in vitro datademonstrate that Ewing sarcoma cells expressing highlevels of aldehyde dehydrogenase (ALDH) have a stemcell phenotype, are resistant to chemotherapy, and thisresistance is overcome by inhibition of mTOR signaling.The goal of this study was to determine if combining anmTOR inhibitor with cytotoxic chemotherapy to targetsarcoma stem cells would improve the survival of patientswith high risk sarcomas.Methods: Patients between the ages of 1 and 80 withmetastatic, unresectable, or recurrent sarcoma for whichno standard curative treatment is available were eligiblefor this study. Subjects were treated with temsirolimusweekly and liposomal doxorubicin monthly. A continualreassessment method design was used to determine theMTD of this combination, and an expansion cohort of patientstreated at the MTD was evaluated for the primaryendpoint of progression-free survival (PFS). Pharmacokineticdata were obtained to investigate potential changes intemsirolimus metabolism in patients treated with concurrentliposomal doxorubicin. Subjects underwent electivetumor biopsy at Week 4 of treatment to evaluate mTORinhibition in the bulk tumor population as well as in thecells with high expression of ALDH.Results: The combination of temsirolimus and liposomaldoxorubicin was well tolerated. The MTD was 30 mg/m2liposomal doxorubicin and 20 mg/m2 temsirolimus. Exposureto sirolimus, the active metabolite of temsirolimus,was substantially higher in subjects treated at the MTDthan has been previously reported for subjects treated withtemsirolimus alone. PFS for subjects treated at the MTDwas longer than has been reported for sarcoma patientstreated with either agent alone. Analysis of biopsy specimensconfirmed mTOR inhibition in vivo.Conclusion: The combination of temsirolimus and liposomaldoxorubicin can be safely administered to patientswith poor risk bone and soft tissue sarcomas, includingheavily pretreated patients. Concurrent administration ofliposomal doxorubicin increases exposure to sirolimus.Biopsy of patients on treatment confirmed mTOR inhibitionin tumors. The combination prolongs PFS comparedto either agent alone.<strong>Poster</strong> #172ACTIONABLE ABERRATIONS IN SARCOMAS ANDTARGET-BASED SELECTION IN CLINICAL TRIALSFilip Janku 1 ; Sarina A. Piha-Paul 1 ; David S. Hong 1 ;Aung Naing 1 ; Jennifer J. Wheler 1 ; Tamara G. Barnes 1 ;Rajyalakshmi Luthra 2 ; Robert S. Benjamin 3 ; Razelle Kurzrock 11Investigational Cancer Therapeutics (Phase I Program),The University of Texas MD Anderson Cancer Center,Houston, TX, USA; 2 Molecular Diagnostic Laboratory,The University of Texas MD Anderson Cancer Center,Houston, TX, USA; 3 Sarcoma Medical <strong>Oncology</strong>,The University of Texas MD Anderson Cancer Center,Houston, TX, USAObjective: Molecular aberrations in BRAF, EGFR, KIT,KRAS, NRAS, MET, PTEN, and TP53 have been identifiedin various malignancies. They confer a survival advantageto cancer cells and some can act as druggable targets forcancer therapy.Methods: Tumor tissue from patients with advanced sarcomas(excluding gastrointestinal stromal tumors) referredto the Phase I Program for targeted therapy beginning in10/08 were, if feasible, analyzed for mutations in BRAF,EGFR, KIT, KRAS, NRAS, MET, TP53 using PCR-basedDNA sequencing and Sequenom MassARRAY and loss ofPTEN function (mutation or loss of staining on immunohistochemistry).Whenever possible, patients were treatedwith a therapy targeted to their molecular abnormality.Results: Overall, tumor samples from 138 patients with257
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