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Epithelioid sarcoma (ES) is an aggressive ultra-rare soft-tissue sarcoma marked by SMARCB1/INI1 deficiency. SMARCB1/INI1 deficiency leads to elevated expression of EZH2, a component of polycomb repressive complex 2, which mediates gene silencing by catalyzing H3K27me3. Tazemetostat is an oral, SAM-competitive inhibitor of EZH2, whose blockade prevents the methylation of histone H3K27, thus decreasing the growth of EZH2 mutated or over-expressing cancer cells. Tazemetostat has been approved for the treatment of patients aged 16 years and older with metastatic or advanced ES not eligible for complete resection, based on the positive results of a single-arm Phase II basket study. Tazemetostat though represents a new treatment option for ES patients, although clinical/molecular predictors of response are still to be identified. The combination of tazemetostat with other drugs like doxorubicin and immunotherapeutic agents is currently under investigation in ES patients.

Background The objective of this study was to report on a retrospective series of patients with epithelioid hemangioendothelioma (EHE) who received treatment with sirolimus within the Italian Rare Cancer Network. Methods From January 2005, 38 adult patients with advanced EHE received continuous-dosing sirolimus, 5 mg daily, until they developed either toxicity or disease progression. Disease progression in the 6 months before the start of treatment was required. Each pathologic diagnosis was reviewed. The daily dose of sirolimus was adjusted based on plasma levels. Response was retrospectively assessed by local investigators using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST). Survival was estimated using the Kaplan-Meier method. Results All 38 patients (WW Domain Containing Transcription Regulator 1 [WWTR1]-positive, n = 37; transcription factor E3 [TFE3]-positive, n = 1) had disease progression before starting sirolimus (at baseline, 13 of 38 patients had the presence of serosal effusions and systemic symptoms). Thirty-seven patients were evaluable for response (there was 1 early interruption). The best RECIST responses were a partial response in 4 patients (10.8%), stable disease in 28 patients (75.7%), and disease progression in 5 patients (13.5%). At a 41.5-month median follow-up (interquartile range [IQR], 23.9-56.8 months), the median PFS was 13 months (95% CI, 3.7 months to not estimated [NE]), and the median OS was 18.8 months (95% CI, 10.6 months to NE). In patients who had serosal effusions at baseline, the median PFS was 4.8 months (IQR, 3.5-11.7 months), and the median OS was 10.6 months (IQR, 5.1-13.0 months), compared with 47.8 months (IQR, 11.4 months to NE) and 47.8 months (IQR, 15.7 months to NE), respectively, in patients without serosal effusions. Overall, sirolimus was fairly well tolerated, with 10 patients reporting irregular menstruation/ovary disfunction. Conclusions The current results confirm that sirolimus is active in EHE, leading to prolonged stabilization in most patients who present without serosal effusions. Serosal effusions are confirmed as an unfavorable prognostic sign associated with short survival, and sirolimus displays limited activity in this subgroup.

[Background] This observational, retrospective effort across Europe, US, Australia, and Asia aimed to assess the activity of systemic therapies in EHE, an ultra-rare sarcoma, marked by WWTR1-CAMTA1 or YAP1-TFE3 fusions., [Methods] Twenty sarcoma reference centres contributed data. Patients with advanced EHE diagnosed from 2000 onwards and treated with systemic therapies, were selected. Local pathologic review and molecular confirmation were required. Radiological response was retrospectively assessed by local investigators according to RECIST. Progression free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method., [Results] Overall, 73 patients were included; 21 had more than one treatment. Thirty-three patients received anthracyclines regimens, achieving 1 (3%) partial response (PR), 25 (76%) stable disease (SD), 7 (21%) progressive disease (PD). The median (m-) PFS and m-OS were 5.5 and 14.3 months respectively. Eleven patients received paclitaxel, achieving 1 (9%) PR, 6 (55%) SD, 4 (36%) PD. The m-PFS and m-OS were 2.9 and 18.6 months, respectively. Twelve patients received pazopanib, achieving 3 (25%) SD, 9 (75%) PD. The m-PFS and m-OS were.2.9 and 8.5 months, respectively. Fifteen patients received INF-α 2b, achieving 1 (7%) PR, 11 (73%) SD, 3 (20%) PD. The m-PFS and m-OS were 8.9 months and 64.3, respectively. Among 27 patients treated with other regimens, 1 PR (ifosfamide) and 9 SD (5 gemcitabine +docetaxel, 2 oral cyclophosphamide, 2 others) were reported., [Conclusion] Systemic therapies available for advanced sarcomas have limited activity in EHE. The identification of new active compounds, especially for rapidly progressive cases, is acutely needed.

Contains fulltext : 220839.pdf (Publisher’s version ) (Closed access) BACKGROUND: Intimal sarcoma (InS) is an exceedingly rare neoplasm with an unfavorable prognosis, for which new potentially active treatments are under development. We report on the activity of anthracycline-based regimens, gemcitabine-based regimens, and pazopanib in patients with InS. METHODS: Seventeen sarcoma reference centers in Europe, the United States, and Japan contributed data to this retrospective analysis. Patients with MDM2-positive InS who were treated with anthracycline-based regimens, gemcitabine-based regimens, or pazopanib between October 2001 and January 2018 were selected. Local pathological review was performed to confirm diagnosis. Response was assessed by RECIST1.1. Recurrence-free survival (RFS), progression-free survival (PFS) and overall survival were computed by Kaplan-Meier method. RESULTS: Seventy-two patients were included (66 anthracycline-based regimens; 26 gemcitabine-based regimens; 12 pazopanib). In the anthracycline-based group, 24 (36%) patients were treated for localized disease, and 42 (64%) patients were treated for advanced disease. The real-world overall response rate (rwORR) was 38%. For patients with localized disease, the median RFS was 14.6 months. For patients with advanced disease, the median PFS was 7.7 months. No anthracycline-related cardiac toxicity was reported in patients with cardiac InS (n = 26). For gemcitabine and pazopanib, the rwORR was 8%, and the median PFS was 3.2 and 3.7 months, respectively. CONCLUSION: This retrospective series shows the activity of anthracycline-based regimens in InS. Of note, anthracyclines were used in patients with cardiac InS with no significant cardiac toxicity. The prognosis in patients with InS remains poor, and new active drugs and treatment strategies are needed.

e23553 Background: DSRCT is an ultra-rare soft tissue sarcoma marked by the presence of the EWS-WT1 translocation and a dismal prognosis. Anecdotal activity of T in DSRCT pts was reported. We describe herein three advanced DSRCT pts treated with T and a comparative assessment of doxorubicin (D), pazopanib (P) and T in a patient-derived xenograft (PDX) model of DSRCT. Methods: Three pts (#1, #2 and #3) suffering from progressive, metastatic, unresectable relapsing disease from a primary peritoneal DSRCT previously treated with 8 cycles of anthracycline-based neoadjuvant chemo and complete surgical resection, were started on T (1.3 mcg/sqm every 3-4 weeks). A PDX model was generated by subcutaneously implanting small tumor fragments obtained at surgery from a treatment-naïve DSRCT patient into the right flank of SCID mice. Consistency of PDX and the originating tumor was confirmed in terms of histomorphology and presence of the EWS-WT1 gene fusion. Mice were randomized to receive D, P and T, administered as single agents at optimal doses and schedules. Drug activity was assessed in terms of tumor volume inhibition (TVI) percentage in treated versus control mice. An orthotopic xenograft model was also generated by injecting DSRCT cells into the peritoneal cavity of SCID mice. Results: At the time of this report, pt #1 and #2 are on therapy with T, with a partial response by RECIST maintained after 48 and 36 months from treatment start, respectively, while #3 progressed after 4 months. In the DSRCT PDX model, T was the most effective drug, with a maximum TVI of 82%, while D and P showed lower, comparable activity (maximum TVI: 59% and 66%, respectively). In the orthotopic DSRCT PDX, DSRCT cells spreading in the abdominal cavity generated different tumor masses, properly recapitulating the dissemination pattern in patients, confirming the reliability of this preclinical model. Conclusions: Both our preliminary model and our further clinical observations support the potential of T in DSRCT. A confirmatory prospective clinical study is now warranted.

Background Despite the efficacy of prophylaxis with serotonin type 3 (5-HT3) receptor antagonists, nausea and vomiting are still among the most common chemotherapy-induced toxicities. The aim of this study was to evaluate the efficacy of adding aprepitant in patients with chemotherapy-induced nausea and vomiting (CINV) refractory to prophylaxis with 5-HT3 receptor antagonists and dexamethasone. Patients and Methods Between January 2008 and November 2010, 51 patients (median age 59 years) with a variety of malignancies (breast cancer: 23; lung cancer: 12; sarcoma: 6; ovarian cancer: 3; other: 7) were enrolled. All patients were refractory to antiemetic therapy according to ASCO guidelines and developed at least grade 2 nausea and/or vomiting after the first chemotherapy course. Aprepitant was given at 125 mg on day 1 and 80 mg on days 2–3. Patients also received a single dose of palonosetron 250 μg on day 1 plus dexamethasone 12–20 mg at a constant dose. Results After addition of aprepitant, the number of patients with grade 3/4 nausea decreased from 31 (61%) to 4 (8%), and those with grade 2 nausea from 20 (39%) to 6 (12%) [both p

[Background] Extraskeletal myxoid chondrosarcoma is a rare sarcoma with low sensitivity to cytotoxic chemotherapy. Retrospective evidence suggests that antiangiogenic drugs could be a treatment option. We aimed to investigate the activity of pazopanib, an antiangiogenic drug, in patients with advanced extraskeletal myxoid chondrosarcoma., [Methods] In this single-arm, open-label phase 2 trial, three parallel independent cohorts of different histotypes of advanced sarcomas were recruited (extraskeletal myxoid chondrosarcoma, typical solitary fibrous tumour, and malignant-dedifferentiated solitary fibrous tumour). In each cohort, patients received pazopanib. In this Article, we report the results of the cohort of patients with advanced extraskeletal myxoid chondrosarcoma. Separate reporting of the three cohorts was prespecified in the study protocol. In this cohort, adult patients (aged ≥18 years) with a diagnosis of NR4A3-translocated, metastatic, or unresectable extraskeletal myxoid chondrosarcoma, who had Response Evaluation Criteria in Solid Tumors (RECIST) progression in the previous 6 months, and had an Eastern Cooperative Oncology Group performance status of 0–2, were enrolled at 11 study sites of the Spanish, Italian, and French sarcoma groups. Patients received oral pazopanib (800 mg/day) continuously, until disease progression, unacceptable toxicity, death, non-compliance, patient refusal, or investigator's decision. The primary endpoint was the proportion of patients achieving an objective response according to RECIST 1·1 in the modified intention-to-treat population (patients who provided consent and had a central molecularly confirmed diagnosis of extraskeletal myxoid chondrosarcoma). The safety analysis included all patients who received at least one dose of pazopanib. This study is registered with ClinicalTrials.gov, number NCT02066285., [Findings] Between June 24, 2014, and Jan 17, 2017, 26 patients entered the study and started pazopanib. Of these, 23 met the eligibility criteria for the modified intention-to-treat analysis. Median follow-up was 27 months (IQR 18–30). 22 patients (one patient died before the primary analysis) were evaluable for the primary endpoint: four (18% [95% CI 1–36]) had a RECIST objective response. No deaths or grade 4 adverse events occurred. The most frequent grade 3 adverse events were hypertension (nine [35%] of 26 patients), increased concentration of alanine aminotransferase (six [23%]), and increased aspartate aminotransferase (five [19%])., [Interpretation] Pazopanib had clinically meaningful antitumour activity in patients with progressive and advanced extraskeletal myxoid chondrosarcoma, and could be considered a suitable option after failure to respond to first-line anthracycline-based chemotherapy in these patients., Funding: Spanish Group for Research on Sarcomas, Italian Sarcoma Group, French Sarcoma Group, GlaxoSmithKline, and Novartis.

Epithelioid sarcoma (ES) is a rare mesenchymal malignancy marked by SMARCB1/INI1 deficiency. Retrospective clinical data report on the activity of anthracycline- and gemcitabine-based regimens. EZH2 inhibitors are currently being tested in clinical trials. Since comparisons of these agents are unlikely to be prospectively evaluated in the clinics, we took advantage of an INI1-deficient proximal-type ES patient-derived xenograft (PDX ES-1) to comparatively assess its preclinical antitumor activity. Mice were treated with doxorubicin and ifosfamide, singly or in combination, gemcitabine, and the EZH2 inhibitor EPZ-011989. Comparable antitumor activity (max tumor volume inhibition: ~90%) was caused by gemcitabine, EPZ-011989, and the doxorubicin&ndash, ifosfamide combination. The integration of RNAseq data, generated on tumors obtained from untreated and EPZ-011989-treated mice, and results from functional studies, carried out on the PDX-derived ES-1 cell line, revealed autophagy induction as a possible survival mechanism in residual tumor cells following EPZ-011989 treatment and identified HMGA2 as a main player in this process. Our data support the clinical use of gemcitabine and the doxorubicin&ndash, ifosfamide combination, confirm EZH2 as a therapeutic target in proximal-type ES, and suggest autophagy as a cytoprotective mechanism against EZH2 inhibition.

Item does not contain fulltext Importance: Epithelioid sarcoma (ES) is an exceedingly rare malignant neoplasm with distinctive pathologic, molecular, and clinical features as well as the potential to respond to new targeted drugs. Little is known on the activity of anthracycline-based regimens, gemcitabine-based regimens, and pazopanib in this disease. Objective: To report on the activity of anthracycline-based regimens, gemcitabine-based regimens, and pazopanib in patients with advanced ES. Design, Setting, and Participants: Seventeen sarcoma reference centers in Europe, the United States, and Japan contributed data to this retrospective analysis of patients with locally advanced/metastatic ES diagnosed between 1990 and 2016. Local pathological review was performed in all cases to confirm diagnosis according to most recent criteria. Exposures: All patients included in the study received anthracycline-based regimens, gemcitabine-based regimens, or pazopanib. Main Outcome and Measures: Response was assessed by RECIST. Progression-free survival (PFS) and overall survival (OS) were computed by Kaplan-Meier method. Classic and proximal subtypes were defined based on morphology (according to 2013 World Health Organization guidelines). Results: Overall, 115 patients were included, 80 (70%) were men and 35 (30%) were women, with a median age of 32 years (range, 15-77 years). Of the 115 patients with ES, 85 were treated with anthracycline-based regimens, 41 with gemcitabine-based regimens, and 18 with pazopanib. Twenty-four received more than 1 treatment. Median follow-up was 34 months. Response rate for anthracycline-based regimens was 22%, with a median PFS of 6 months. One complete response (CR) was reported. A trend toward a higher response rate was noticed in morphological proximal type (26%) vs classic type (19%) and in proximal vs distal primary site (26% vs 18%). The response rate for gemcitabine-based regimens was 27%, with 2 CR and a median PFS of 4 months. In this group, a trend toward a higher response rate was reported in classic vs proximal morphological type (30% vs 22%) and in distal vs proximal primary site (40% vs 14%). In the pazopanib group, no objective responses were seen, and median PFS was 3 months. Conclusions and Relevance: This is the largest retrospective series of systemic therapy in ES. We confirm a moderate activity of anthracycline-based and gemcitabine-based regimens in ES, with a similar response rate and PFS in both groups. The value of pazopanib was low. These data may serve as a benchmark for trials of novel agents in ES.

11065 Background: To report on a multi-institution retrospective study on the activity of anthracycline-based (Ab) and gemcitabine-based (Gb) regimens as well as pazopanib (P) in patients with advanced epithelioid sarcoma (ES) treated within 16 sarcoma reference centres in Europe, US and Japan. Methods: Patients with a histologically confirmed diagnosis of locally advanced/metastatic ES were selected. Classic and distal subtypes were defined based on morphology (WHO 2014). INI1 expression is under evaluation.Response was evaluated by RECIST.Progression-free survival (PFS) and overall survival (OS) were computed by Kaplan-Meier method. Results: Ninety ES patients were identified (Table 1). They were treated with Ab (72), Gb (30) and P (20); 25 pts received more than one treatment. The median follow-up for Ab, Gb and P groups was 32, 24 and 22 months, respectively. The response rate (RR) for Ab was 25% (95% CI 16%-37%), with a median PFS and OS of 6 and 17 months. The RR for Gb was 23% (95% CI 10% - 42%), with 1 complete response and a median PFS and OS of 5 and 20 months. In the P group, no objective responses were reported, and median PFS and OS were 3 and 9 months. A non-statistically significant trend towards a greater RR in proximal than classic subtype was seen in both Ab (27% vs 22%) and Gb (30% vs 13%) groups. Conclusions: This retrospective series, the largest currently available, confirms the activity of Ab and Gb in ES, with a similar RR and PFS in both groups. In this population, the value of P seems limited. These data may serve as a benchmark for trials of novel agents in ES. [Table: see text]

Perivascular epithelioid cell tumor (PEComa) is a family of mesenchymal tumors. Conventional chemotherapy has little activity in this disease, but case reports are available on the activity of mammalian target of rapamycin inhibitors (e.g. sirolimus and temsirolimus). Pharmacokinetic assays of sirolimus are available as this drug has a precise therapeutic window and blood levels might be influenced by CYP3A4 polymorphisms and drug interactions. We report on a case of a patient with metastatic, progressive PEComa who started sirolimus at a dose of 5 mg/day with evidence of grade (G) 3 mucositis, G2 thrombocytopenia, and G1 leucopenia 10 days after the treatment started, in absence of concomitant medications or prohibited food assumption. Elevated sirolimus blood levels were detected (156.8 ng/ml). Sirolimus was stopped, and toxicity resolved in 5 weeks. Computed tomography scan 2 months after the treatment started showed a partial response (RECIST). After toxicity resolution, the patient restarted sirolimus at a dose of 1 mg/day, with blood levels in the range of 10-20 ng/ml. Tumor response was confirmed and maintained, and the patient is still under treatment 18 months later, with no additional adverse effects. Genetic analysis of five selected polymorphisms (rs2740574, rs776746, rs1128503, rs2032582, and rs1045642) in drug metabolism enzymes and transporters did not provide a clear explanation of the observed unusual pharmacokinetic. This case confirms the activity of mammalian target of rapamycin inhibitors in PEComa and strengthens the importance of pharmacokinetic drug blood levels monitoring in patients treated with sirolimus. In our patient, after dose adjustment, sirolimus could be restarted with a prolonged clinical benefit and no additional toxicity.

Background: Scientific data provide the evidence that secondary K-RAS mutations do not occur during anti-epidermal growth factor receptor therapy in colorectal cancer patients. This multicenter phase II prospective study aims to investigate the activity of a retreatment with a cetuximab-based therapy. Patients and methods: We enrolled 39 irinotecan-refractory patients who had a clinical benefit after a line of cetuximab- plus irinotecan-based therapy and then a progression of disease for which underwent a new line chemotherapy and finally, after a clear new progression of disease, were retreated with the same cetuximab- plus irinotecan-based therapy. Results: Median number of therapeutic lines before accrual was 4. Median interval time between last cycle of first cetuximab-based therapy and first cycle of the retreatment was 6 months. Overall response rate was 53.8% with 19 partial responses (48.7%) and 2 complete responses (5.1%). Disease stabilization was obtained in 35.9% of patients and progression in four patients (10.2%). Median progression-free survival was 6.6 months. The correlation between skin toxicity during first cetuximab therapy and during cetuximab rechallenge was significant (P = 0.01). Conclusion: Rechallenge with the same cetuximab-based therapy may achieve a new important clinical benefit further delaying the progression of disease and improving the therapeutic options. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Objectives Giant cell tumour of bone (GCTB) is a rare tumour, generally managed with surgery. Treatment of the very rare unresectable advanced/metastatic GCTB is challenging and denosumab is the only current available medical option, an anti-RANKL monoclonal antibody inhibiting osteolysis. An uncommon but severe and treatment-limiting adverse event of denosumab is the osteonecrosis of the jaw (ONJ). The clinical management of GCTB patients stopping denosumab for medication-related (MR)-ONJ and the possible reintroduction of denosumab after MR-ONJ resolution is matter of debate. We performed a retrospective study to describe the incidence, clinical features and outcome of MR-ONJ in unresectable GCTB patients treated with denosumab at our Institution. Design and setting Retrospective, single-institutional study. Participants Adult patients receiving denosumab as antineoplastic therapy for GCTB and experiencing MR-ONJ at Fondazione IRCCS Istituto Nazionale Tumori of Milan between January 2008 and July 2019. Main outcome measures Incidence, time of onset and clinical features of MR-ONJ. Results 29 patients with locally advanced and/or metastatic GCTB treated with denosumab were identified. At a median follow-up of 70 months (range 1–125), 4 (13.8%) patients experienced MR-ONJ while on treatment, after 125, 119, 85 and 41 months of denosumab, respectively. All patients showed an ongoing tumour stabilisation with denosumab at the MR-ONJ onset and in all cases denosumab was stopped. All four patients were treated with ozone therapy. Two are waiting for surgery, two were already operated on. Both of them experienced disease progression and were thus rechallenged with denosumab. One is still on therapy after 25 months. The other had an MR-ONJ relapse after 39 months and was treated again with ozone therapy and surgery. She is under surveillance, GCTB being currently stable. Conclusion A clinical algorithm of denosumab rechallenge after complete resolution of MR-ONJ in progressing GCTB patients should be prospectively validated.

11065 Background: EHE is an exceedingly rare soft tissue sarcoma (STS) with no active standard treatment available in advanced patients (pts). We already reported on the activity of sirolimus in a retrospective series of 18 EHE treated within the RTR. We herein update this series on a longer follow-up in a larger number of pts. Methods: Adult pts affected by an advanced, progressive and centrally confirmed EHE treated with sirolimus within the RTR from 2006 to 2018 were retrospectively reviewed. Sirolimus was administered at the starting dose of 5 mg/day, until toxicity or progression. Sirolimus dose was adjusted according to plasma levels (target: 15–20 ng/dL). Response was assessed by RECIST 1.1. Survival was estimated by Kaplan-Meier method. Results: 33 patients were retrospectively identified (median age = 47 years, female = 20 (60%), male = 13 (40%); pretreated = 8, naïve = 25; presence of pleural effusion at baseline = 6). All patients had metastatic disease and evidence of disease progression before starting sirolimus. Mean sirolimus daily dose was 5 mg (range 2-10). 9 pts are still on therapy, 24 stopped sirolimus (13 progression, 5 toxicity, 6 other). 31 pts were evaluable for response (2 pts too early). Best RECIST response was: 1 (3.2%), PR, 26 (83.8%) SD, 4 (12.9%) progression. At a 14-mo median FU, median PFS (m-PFS) was 12.3 mos (range 8–15) and median OS (m-OS) was 19 mos (range 1–40). Pleural effusion correlated with a short m-PFS (3.4 vs 14.3 mos in patients without pleural effusion, p = 0.006) and m-OS (10.6 vs 40 mos in patients without pleural effusion, p 24 mos was 23%, with 54 % being alive. Conclusions: We selected pts with advanced EHE with clear evidence of disease progression. This singles out a subgroup of EHE pts with a bad prognosis. Prognosis was shown to be exceedingly bad when there was evidence of serosal effusion, and sirolimus was not effective. Though in an uncontrolled setting, apparently sirolimus is able to slightly prolong PFS and, above all, to allow mid-term freedom of progression in roughly 25% of pts.

11062 Background: Extraskeletal myxoid chondrosarcoma (EMC) is an exceedingly rare sarcoma, marked by a specific translocation involving the gene NR4A3 that can be rearranged with different partners. Preliminary retrospective data suggest that sunitinib is active, but no formal prospective studies are available. We report on a multicentric European prospective, investigator-driven, Phase 2 study on pazopanib (P) in NR4A3+ advanced EMC patients (pts), carried out by the Spanish, Italian and French Sarcoma groups. Methods: From June 2014 to November 2016, 24 advanced EMC pts entered this study (median age: 64 yrs - disease extent: metastatic 77%, locally advanced 23% - prior medical treatment: 18 (86%) naive; 2 (9%) 1 line, 1 (5%) > 1 line). Path diagnosis and NR4A3 rearrangement (FISH and/or real-time PCR analysis) were centrally confirmed. Pts received P 800 mg/day (relative dose intensity = 0,82%, 658 mg/day), until progression or toxicity. The primary study end-point was response rate as per RECIST 1.1. Secondary end-points were overall survival, progression-free survival (PFS), clinical benefit rate (CBR) (RECIST CR+PR+SD≥6mos). An exploratory evaluation of the correlation between the rearrangement subtype and the outcome is ongoing. Results: 20/24 pts were evaluable for response (1 early death; 3 too early). One patient (5%) had a partial response, 17 (75%) stable disease, 2 (10%) progression as their best RECIST responses. At the time of this analysis, 12 pts were still under treatment, while 12 interrupted P (10 progression, 1 toxicity, 1 other). At a 13-month median follow-up, the median PFS was 13 months (range 1.6-25.1), with 29% pts progression-free at 18 months and a 65% CBR. Median OS was not reached. Conclusions: This Phase 2 study is formally negative since the target of at least 3/21 RECIST responses was not reached. However, looking at PFS, P was associated with a prolonged disease stabilization in a significant proportion of pts. This suggests to further explore the use of P in EMC. Clinical trial information: NCT02066285.

Oxaliplatin-induced neuropathy is a dose-related side effect which occurs in almost 40 % of patients treated with oxaliplatin. Aim of the present study was to identify reliable clinical factors predicting its development and duration.One hundred sixty-nine completely resected colorectal cancer patients treated with adjuvant Folfox IV regimen were retrospectively included. The following pre-treatment clinical parameters were collected: hypocalcaemia, hypomagnesaemia, hypoalbuminaemia, anaemia, diabetes, chronic renal failure (CRF), folate deficiency, vitamin B(12) deficiency, number of cycles received and habit to alcohol consumption. Incidence, grade (NCI-CTCAE v.3) and duration of neuropathy were recorded.Incidence of neuropathy was found to be higher in patients with pre-treatment anaemia (p = 0.001), hypoalbuminaemia (p = 0.01) and hypomagnesaemia (p = 0.001) as well in those with habit to alcohol consumption (p = 0.003). Neuropathy durations were conversely associated with age, being longer in younger patients (p = 0.03), and again with hypoalbuminaemia (p = 0.04) and hypomagnesaemia (p = 0.002). No correlation was found with gender, hypocalcaemia, diabetes and CRF. The correlation between vitamin B(12) and folate levels and the development of neurotoxicity were not analysed because of the high number of missing data in the population.Age, anaemia, hypoalbuminaemia, hypomagnesaemia and alcohol consumption are reliable and easily assessable clinical factors predicting incidence and length of oxaliplatin-induced neuropathy.

Itch is a common side-effect of treatment with anti-EGFR antibodies and tyrosine-kinase inhibitors. We designed a pilot single-centre study to assess the effects of aprepitant-a neurokinin receptor inhibitor-for management of severe pruritus induced by biological drugs.In this single-group, prospective study, we consecutively enrolled 45 outpatients with metastatic solid tumours treated with biological drugs at the Campus Bio-Medico Hospital of Rome, Rome, Italy, between September, 2010, and November, 2011. We classified patients into two groups: a refactory group, for patients with pruritis refractory to standard treatment, or a naive group, for patients who had not been previously treated for pruritis. Aprepitant (125 mg on day 1; 80 mg on day 3; 80 mg on day 5) was given to patients in the refractory group after at least 1 week of standard systemic treatment. In the naive group, aprepitant was given in the same schedule as the refractory group, after first onset of severe pruritus. Intensity of itch was evaluated by Visual Analogue Scale (VAS) score. The primary endpoint was change in median VAS score. This trial is registered with ClinicalTrials.gov, number NCT01683552.Median VAS in the refractory group was 8·00 (95% CI 7·93-8·57) at baseline and 1·00 (0·00-2·00) after 1 week of treatment with aprepitant (p0·0001). In the naive group, VAS score was 8·00 (7·43-8·37) at baseline and 0·00 (0·06-1·08) after 1 week of treatment (p0·0001). 41 (91%) patients responded to aprepitant (ie, had a50% reduction in intensity of pruritis) and pruritus recurred in only six (13%) patients. No adverse events related to aprepitant occurred.Aprepitant decreases severe pruritus induced by biological treatments; it is an old drug, widely available, and therefore easy to add to the armamentarium of supportive treatment. Although to our knowledge no other studies of the anti-itch activity of aprepitant are planned, the results of our trial warrant confirmation in phase 2 and 3 trials.None.

11578Background: ES is a rare soft tissue sarcoma with two variants, i.e., the proximal and the distal. Retrospective data on the activity of anthracycline- and G-based regimens are available. EZH2...

Soft tissue sarcomas are rare mesenchymal tumors accounting for1% of all adult neoplasia. In the last decade, locally advanced and metastatic soft tissue sarcoma have been managed only through surgery, radiotherapy and standard chemotherapy (mainly based on anthracycline and ifosfamide). Despite the efforts, overall 5-year survival rate in patients with soft tissue sarcomas of all stages remains only 50 - 60%.In the present article, all the main new molecules under clinical evaluation for the treatment of soft tissue sarcoma are revised by describing the mechanism of action, the biological rationale of their use in sarcoma and by reporting the available data about safety and efficacy, up to 2009.A brief summary of the standard treatments available at the moment and a complete analysis of the state of art about the development of new target therapies in the management of soft tissue sarcoma.The identification of new biological therapies that target soft tissue sarcoma tumorigenesis key points seems to offer a real opportunity of improving the prognosis of this often aggressive disease. In this sense, the best management for soft tissue sarcoma patients is in a clinical trial and participation in clinical trials should be encouraged.

We report a case of a 74-year-old man with a metastatic anaplastic pancreatic carcinoma (APC). After an early tumour progression on first-line chemotherapy with cisplatin and gemcitabine, even though it was badly tolerated, he was treated with a combination of systemic modified FOLFIRI and high-intensity focused ultrasound (HIFU) on the pancreatic mass. A tumour showing partial response with a clinical benefit was obtained. HIFU was preferred to radiotherapy because of its shorter course and minimal side effects, in order to improve the patient’s clinical conditions. The patient is currently on chemotherapy, asymptomatic with a good performance status. In referral centres, with specific expertise, HIFU could be safely and successfully combined with systemic chemotherapy for treatment of metastatic pancreatic carcinoma.

Following progression on first-line platinum and fluoropyrimidine-based chemotherapy, prognosis for advanced gastric cancer patients is extremely poor. Thus, new and effective treatments are required. Based on positive results of recent randomized controlled trials, second-line monochemotherapies with either irinotecan or taxanes confer a median overall survival of approximately 5 months in gastro-esophageal and gastric adenocarcinoma. Combination of weekly paclitaxel and ramucirumab, a novel anti-angiogenic VEGFR2 antibody, pushes the overall survival up to over 9.5 months, whereas apatinib, a novel oral VEGFR2 tyrosine kinase inhibitor, seems to be promising in heavily pretreated patients. In contrast, the role of EGFR/HER2 and mTOR inhibitors is controversial. Studies are heterogeneous for tumor population, geographical areas, quality of life assessment, type of first-line therapy and response to that, making clinical practice application of the trial results difficult. Furthermore, sustainability is challenging due to high cost of novel biotherapies.

Pegfilgrastim is regarded today as the standard therapy in the primary prophylaxis of febrile neutropenia induced by three-weekly chemotherapy regimens while its use with biweekly regimens is still...

Elevation in liver transaminases is common in patients treated with the marine antitumor agent trabectedin. However, the impact of trabectedin-related transaminase elevations on treatment outcomes is unclear. This retrospective study investigated the correlation between liver tests abnormalities and treatment outcomes in patients with unresectable advanced or metastatic soft tissue sarcomas (STS) treated with trabectedin 1.5 mg/m2 once every 3 weeks at three reference centers in Italy. The effect of grade 3/4 elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) during the first two cycles and at any time during trabectedin treatment on progression-free survival (PFS) and overall survival (OS) were analyzed. Liver tests abnormalities during the first two cycles of chemotherapy or at any time during trabectedin treatment did not significantly affect PFS or OS. Nor were survival outcomes significantly different in the subgroups of patients with or without ALT/AST increases or with ALT/AST elevations ≥15 × the upper limit of normal (ULN) versus those with ALT/AST elevation

Background Ipilimumab is a fully human monoclonal antibody directed against cytotoxic T-lymphocyte antigen-4 , a key negative regulator of T-cell activation approved by the Food and Drug Administration as of March 2011 for the treatment of metastatic melanoma. As a result of the up-regulation of the immune system, several immune-mediated adverse effects have been reported including colitis, dermatitis, hepatitis and rarely hypophysitis. The most frequent immune-mediated adverse effects described in literature include gastrointestinal toxicity such as diarrhea, colitis and case of colitis and ileitis. Case presentation In this paper we report an interesting case of immune-mediate ileitis without colitis in a 54 years old woman with metastatic melanoma treated with ipilimumab. We also discuss about case management and the possible pathological mechanisms considering also previous reports. Conclusions The aim of this article is to support further investigations concerning epigenetic and genetic analysis in order to personalize biological therapy and to reduce immune related adverse events observed after ipilimumab administration.

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Contains fulltext : 136490.pdf (Publisher’s version ) (Open Access) BACKGROUND: We retrospectively reviewed data from nine pre-treated metastatic desmoplastic small round cell tumour (DSRCT) patients who received pazopanib. PATIENTS AND METHODS: Three patients received pazopanib within the EORTC phase II 62043, three in the EORTC phase III 62072, and three in the context of UK named patient program. RESULTS: Nine patients were retrieved from the databases, the median age was 30 years (range: 21-47), they were all males. All had received prior chemotherapy. At the time of treatment start, 4 patients (44%) had ECOG PS 0, 4 (44%) PS 1, 1 (11%) PS 2. Best response was partial response (PR) in 2/9 (22%) patients, stable disease (SD) in 5/9 (56%) and progressive disease (PD) in 2/9 (22%) with a clinical benefit rate (PR + SD > 12 weeks) of 78%. Median PFS and OS were 9.2 (95%CI: 0-23.2) and 15.4 (95%CI: 1.5-29.3) months respectively. With a median follow-up of 20 months, 2/9 (22%) patients are still alive, all progressed. The most common toxicities included neutropenia (G1-2 45%; G3-4 11%), anaemia (G1-2 45%), fatigue (G1-2 67%), diarrhoea (G1-2 45%; G3-4 11%), nausea (G1-2 45%), hypertension (G1-2 45%) and increase in liver enzymes (G1-2 34%; G3-4 11%). Three patients (34%) required a dose reduction. One of the patients discontinued treatment because of persistent increase in total bilirubin level, one due to patient's choice. CONCLUSION: In this series, pazopanib showed interesting activity in DSRCT patients who progressed after prior chemotherapy without major toxicity.

Sunitinib has previously been reported to be potentially effective in the treatment of malignant melanomas expressing c-KIT. Here we report on the case of a 77-year-old gentleman affected by a metastatic clear cell carcinoma of the kidney and a metastatic malignant melanoma with liver and lung metastases. Despite the negativity for CD117 and the absence of KIT amplification or mutations in the melanoma specimen, he achieved a partial response both in the lungs and in the liver while on sunitinib (50 mg once/day, 4 weeks on/2 weeks off) for the treatment of kidney cancer. To our knowledge, this represents the first evidence of sunitinib activity in KIT wild-type melanoma. Further studies should be performed to confirm these preliminary data.

To report on the anti-tumour activity and toxicity of sorafenib combined with dacarbazine in patients with pre-treated advanced soft tissue sarcoma (STSs).From November 2009 to December 2010, 17 patients affected by STSs who had failed two or more regimen of chemotherapy, with a performance status ≤ 2 and measurable disease were consecutively enrolled in the present case series. Sorafenib was administered at 400 mg b.i.d. continuous dosing in combination with dacarbazine, 300 mg/m(2) for three consecutive days every 21 days until disease progression or intolerable toxicity.Fourteen patients were evaluable for response. Three patients stopped treatment early and were not evaluable for response. One of them died for not disease-dependent reason, the other two went off-study due to rapid clinical worsening, without performing radiologic evaluation. No complete responses were registered. As by RECIST, partial responses (PR) were observed in three patients (21%), stable disease (SD) in six patients (43%) and progressive disease (PD) in five patients (36%), with a clinical benefit rate (RECIST PR+SD6 months) of 64%. The median time of progression was 20 weeks (range: 9 - 34 weeks) and the median overall survival was 43 weeks (range: 17 - 65 weeks). The main toxicities were neutropenia (36%), thrombocytopenia (36%), hypertension (36%), fatigue (50%) and skin reactions (57%). Five patients required dose reductions (both dacarbazine and sorafenib) for toxicity and three patients required only sorafenib reduction for dermatologic reactions. One patient was taken off-study because of severe sorafenib-related dermatologic toxicity.Sorafenib and dacarbazine combination seems to be an active and safety regimen in pre-treated STSs. A Phase II trial is ongoing in patient affected by selected sarcoma subtypes.

PML regulates a wide range of pathways involved in tumorigenesis, such as apoptosis, which is also one of the main mechanisms through which oxaliplatin and fluoropyrimidine exert their antineoplastic activity. The present study aims to investigate PML expression as a predictive factor of oxaliplatin/fluoropyrimidine therapy efficacy. Seventy-four metastatic colorectal cancer patients who received oxaliplatin/floropyrimidine-based first line therapy have been included in this retrospective study. PML expression was assessed by immunohistochemistry. PML down-regulation was detected in 39 (52.7%) patients (14 complete and 25 partial PML loss). RR was significantly lower (25.6%) in patients with PML down-regulation than in patients with preserved PML expression (60%) (P = 0.006). Median TTP was 5.5 months when PML was down-regulated versus 11.9 months in case of preserved PML expression (P

Hepatic toxicity is often related to chemotherapy agent administration, and it represents one of the principal causes of dose reduction and chemotherapy delays or discontinuation. S-Adenosyl methionine (AdoMet) supplementation is effective in the treatment of a variety of liver injuries, but it has never been evaluated in the prevention of chemotherapy-induced liver damage.A total of 105 patients affected by resected colorectal cancer (CRC) were enrolled. Forty-five were treated with FOLFOX IV adjuvant regimen without administering AdoMet, 60 were treated with the same regimen plus supplementation with AdoMet. Liver enzyme levels were assessed before starting the treatment and every therapy cycle. Liver toxicity, chemotherapy course delays, discontinuations and dose reductions due to liver toxicity were recorded.Aspartate aminotransferase (AST) (p0.001), alanine transaminase (ALT) (p = 0.003), bilirubin (p = 0.04) and gamma-glutamyltransferase (γ-GT) (p = 0.002) median level at the end of adjuvant therapy were significantly lower in patients treated with Adome. Patients supplemented with AdoMet experimented a lower grade of liver toxicity (p = 0.002) and had a reduced need of course delay (p0.0001) and dose reduction (p = 0.031).The results of our study demonstrate a protective effect of AdoMet supplementation in patients affected by resected CRC treated with FOLFOX IV adjuvant regimen.

Hepatotoxicity represents a frequent chemotherapy-related side effect, often associated with course delays, discontinuations, and dose reductions. S-adenosylmethionine (AdoMet) administration is effective in the treatment of a variety of liver injuries, but it has never been evaluated in the prevention of chemotherapy-induced damage.Seventy-eight patients affected by metastatic colorectal cancer were enrolled. Forty-two patients were treated with bevacizumab and XELOX without administering AdoMet, 32 were treated with the same regimen plus supplementation with AdoMet. Liver enzymes levels were assessed before starting the treatment, and then every therapy cycle, liver toxicity, chemotherapy course delays, discontinuations, and dose reductions due to liver toxicity were recorded.Aspartate aminotransferase (P = 0.02), alanine transaminase (P0.001), lactate dehydrogenase (P = 0.008), total bilirubin (P = 0.03), and gamma-glutamyltransferase (P0.001) were found to be significantly lower in patients treated with AdoMet than in those who were not. Patients supplemented with AdoMet experimented a lower grade of liver toxicity (P = 0.009) and had a reduced need of course delay (P = 0.042) and dose reduction (P = 0.051).AdoMet supplementation in patients affected by metastatic colorectal cancer treated with oxaliplatin-based regimen seems to be effective in the prevention of chemotherapy-induced liver injury.

Introduction. Sorafenib is an oral multikinase inhibitor that targets Raf kinase and receptor tyrosine kinases and has led to a longer median overall survival (OS) time and time to progression (TTP) in patients with advanced hepatocellular carcinoma (HCC). This study was conducted to assess the link between the antitumor efficacy of sorafenib and its early cutaneous side effects in advanced HCC patients. Materials and Methods. All patients received 800 mg daily of sorafenib until progression or unacceptable toxicities. We retrospectively analyzed the incidence of rash and hand–foot skin reactions (HFSR) during the first month of treatment, comparing tumor control (partial response plus stable disease) and TTP. Results. Sixty-five HCC patients treated with sorafenib were included in this analysis: 47 (73.3%) received sorafenib after failure of some local treatment, whereas 18 (27.7%) received it as first-line treatment. Twenty-nine patients developed at least grade 1 skin toxicity (rash, 13; HFSR, 16). In patients who developed skin toxicity, the tumor control rate was 48.3%, versus 19.4% in patients without cutaneous side effects. The median TTP was 8.1 months in the group of patients with skin toxicity versus 4.0 months in those without skin toxicity. This difference was also statistically significant on multivariate analysis. A borderline statistically significant difference was also observed in terms of OS in patients with early skin toxicity. Conclusions. Skin toxicity should be closely monitored in HCC patients treated with sorafenib in relation to its potential role as a surrogate marker of efficacy.

Ecteinascidin-743 (trabectedin, Yondelis®; PharmaMar, Madrid, Spain), a 25-year-old antineoplastic alkylating agent, has recently shown unexpected and interesting mechanisms of action. Trabectedin causes perturbation in the transcription of inducible genes (e.g., the multidrug resistance gene MDR1) and interaction with DNA repair mechanisms (e.g., the nucleotide excision repair pathway) owing to drug-related DNA double strand breaks and adduct formation. Trabectedin was the first antineoplastic agent from a marine source (namely, the Caribbean tunicate Ecteinascidia turbinata) to receive marketing authorization. This article summarizes the mechanisms of action, the complex metabolism, the main toxicities, the preclinical and clinical evidences of its antineoplastic effects in different types of cancer and, finally, the future perspectives of this promising drug.

e15174 Background: Capecitabine (CAP) and temozolomide (TEM) have been reported to be active as first-line treatment in pancreatic neuroendocrine neoplasms (pNENs). We retrospectively evaluated act...

Bronchial carcinoids (BCs), comprising typical (TC) and atypical (AC) carcinoids, account for 1–2 % of all lung cancers and approximately 20–30 % of all neuroendocrine neoplasms (NENs). They represent the low- and intermediate-grade lung NENs, whereas small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC) represent the high-grade entities. While the prognosis of BCs is favourable at early stages, it is poor when distant metastases are present. Unfortunately, there is a lack of therapeutic options as well as limited data to support the use of standard therapies and sequences of treatments. Some chemotherapeutic regimens have been reported to be active, but their efficacy has not been validated so far. Somatostatin analogues (SSAs) as single agents can be an option for very slow-growing disease, but their role in combination with other therapies has not been established. Among the new targeted agents, data from clinical trials showed that everolimus is a promising one.

Aim: A transient increase in liver enzymes is a well described side effect developed by almost 40% of soft tissue sarcoma (STS) patients treated with trabectedin, often leading to treatment delays or discontinuation. We retrospectively analysed the correlation between trabectedin-related liver toxicity and treatment outcome. Methods: Data from a total of 113 patients receiving trabectedin administered at the dose of 1.5 mg/m2 iv 24 hours in 3 reference centers were evaluated. This exploratory analysis was performed to assess the impact of liver toxicity (grade 3-4 AST and ALT increases) on the trabectedin efficacy and outcome in STS patients. All the patients included had metastatic disease or locally advanced inoperable and received at least one previous line of treatment containing anthracycline. All patients received standard steroids premedication. Results: Median age was 57 years (range: 27-79 ys) and male/female ratio was 71/42. STS histologies were: liposarcoma 32 cases, leiomiosarcoma 27, pleomorphic sarcoma 17, synovial sarcoma 13, 24 other histologies. For 45 patients a G3-4 ALT increase in the first two cycles was reported while for 68 was not. Calculations show that hazard ratios for PFS and OS are not statistically significant (HR=1.124; p=0.734 and HR=0.104; p=0.850, respectively). Furthermore, the analysis was repeated dividing the population between patients with G3-4 ALT elevation during treatment vs. patients without such elevation. Again, hazard ratios for PFS and OS are not statistically significant (HR=0.791; p=0.309 and HR=0.930; p=0.810930, respectively). Finally, the analyses was repeated, splitting the population in patients with peak>15 ULN vs. patients with peak Conclusions: Liver toxicity is a common event during treatment with trabectedin and does not affect outcome. These results should discourage the premature discontinuation of the drug due to the increase in liver enzymes. Disclosure: All authors have declared no conflicts of interest.

Fluoropyrimidines, oxaliplatin, irinotecan and biologic therapies (Bevacizumab, Panitumumab, and Cetuximab) represent the backbone of metastatic colorectal cancer (CRC) treatment. The improvement in survival for mCRC patient led to two main outstanding issues: 1) there is a significant number of patients progressing beyond the third or fourth line of treatment still suitable for further therapy when enrollment into clinical trial is not possible. In this situation, the role of any therapy rechallenge (either chemotherapy alone, chemotherapy and biologic therapy or biologic therapy alone) is still not clear, particularly in patients who had previously responded, and if treatment choice is based on traditional dogma of primary and secondary resistance, rechallenge does not seem to be justified. 2) Prolonged intensive treatment is burdened from the high risk of cumulative toxicity, worsening in quality of life and a not well defined possibility of early acquired resistance. Different hypothesis could justify the research of different strategy in treatment of mCRC: 1) Epigenetic changes might drive resistance and treatment could induce these changes. Re-expression of silenced tumor suppressive genes might resensitize tumors to therapy. It is therefore possible that a drug holiday (intermittent treatment) could allow reversion to a previous epigenetic profile. Moreover an intermittent treatment could delay acquired resistance. 2) It is plausible that tumor grows as a polyclonal mass. If it responds but then becomes resistant to one or more treatments, retreatment might be successful if changing therapies allows to that clone of cells to re-emerge. On these basis, we focused this review on the actual evidences in management of mCRC patients in terms of chemotherapy or biological therapies rechallenge and intermittent treatment. Moreover, we will discuss the potential biological mechanisms of the observed results of early clinical trials.

e14135 Background: Oxaliplatin-induced neuropathy is a dose-related side effect which occurs in almost 40% of patients treated with oxaliplatin. Aim of the present study was to identify reliable clinical factors predicting its development and duration. Methods: 169 completely resected CRC patients treated with adjuvant Folfox IV regimen were retrospectively included. The following pre-treatment clinical parameters were collected: hypocalcemia, hypomagnesaemia, hypoalbuminemia, anaemia, diabetes, chronic renal failure (CRF), folate deficiency, B12 deficiency, number of cycles received and habit to alcohol consumption. Incidence, grade (NCI-CTCAE v.3) and duration of neuropathy were recorded. Results: Incidence of neuropathy was found to be higher in patients with pretreatment anaemia (p=0.001), hypoalbuminemia (p=0.01) and hypomagnesemia (p=0.001) as well in those with habit to alcohol consumption (p=0.003). Neuropathy durations was conversely associated with age, being longer in younger patients (p=0.03), and again with hypoalbuminemia (p=0.04) and hypomagnesemia (p=0.002). No correlation was found with gender, hypocalcemia, diabetes and CRF. The correlation between vitamin B12 and folate levels and the development of neurotoxicity was not analysed because of the high number of missing data in the population. Conclusions: Age, anaemia, hypoalbuminemia, hypomagnesemia and alcohol consumption are reliable and easily assessable clinical factors predicting incidence and length of oxaliplatin induced neuropathy.

10063 Background: Given the limited data currently available, we surveyed the natural history of bone metastases in patients affected by soft tissue sarcoma (STS). Methods: This retrospective, multicenter, observational study evaluated data from 135 patients with STS metastatic to the bone who presented between 2001 and 2011. For all patients, we recorded the primary tumor histological subtype, bone metastases characteristics (onset, site), type of treatment received (surgery, radiotherapy, zoledronic acid), type and frequency of skeletal related events (SRE) and disease outcome. Results: The most represented histological subtypes among the enrolled patients were leiomyosarcoma (27%), angiosarcoma (13%) and spindle cell sarcoma (8%). The spine was the most common site for bone involvement (51%), followed by hip/pelvis (20%), long bones (15%) and other sites (14%). In 27% of cases, bone metastases were present at the time of diagnosis. Fiftyfour patients (40%) developed SREs and the median time to first SRE (if developed) was 4 months. The most common SRE was the need for radiotherapy occurring in 28% of patients followed by pathologic fracture (22%). Patients survived for a median of 6 months after bone metastases diagnosis. The occurrence of a SRE was associated with a decreased overall survival (P=0.04). A subgroup analysis revealed that zoledronic acid significantly prolonged median time to first SRE (5 versus 2 months; P = 0.002). Conversely, It did not determine an improvement in terms of overall survival, even if favorable trend was identified (median, 7 versus 5 months, respectively; P = 0.105). Conclusions: This study illustrates the burden of bone disease from STS and supports the use of zoledronic acid in this setting.

9078 Background: Increasing evidences prove the involvement of keratinocytes NK1 receptors in the pathogenesis of pruritus: this prospective study aims to evaluate the role of aprepitant, a NK1 rec...

Background: Desmoplastic small round cell tumour (DSRCT) is a rare sarcoma typically affecting young males and usually widely metastatic at presentation. Despite multimodal treatment approaches, the prognosis for DSRCT is extremely poor. Alkylator- and anthracyclines- based regimens are widely used as therapy and an initial response is common. Durable responses are exceptionally rare so further systemic treatment options for these patients represent an unmet medical need. We report two cases of metastatic, pretreated DSRCT patients achieving disease stabilisation with Trabectedin. Methods: Retrospective review of 2 patients with progressive DSRCT, treated with Trabectedin. Results: Two males aged 19 and 23 years treated with Trabectedin, 1.5 mg/m 2 over 24 hours 3 weekly for 6 and 5 cycles respectively. Best responses were stable disease in patient 1 and partial response (RECIST 1.1) in patient 2. Progression free survival was 4 months in both cases. Persistent neutropenia required 4 weekly administration in one patient but no other grade 3-4 toxicities occurred. Conclusions: This report supports Trabectedin to be active and safe in pre-treated DSRCT patients. Further prospective and collaborative efforts are desirable to better define its role in the management of this disease.