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TPS345 Background: In the TROPIC trial, cabazitaxel (CAB) plus daily prednisone (PDN) was associated with a significant advantage in OS and PFS in docetaxel (DOC)-pretreated patients (Pts). Whether daily PDN may significantly contribute to CAB efficacy or improve its safety profile is unknown. In the CHARTEED trial, DOC was administered without daily PDN with no concerns about the lack of efficacy or greater toxicity. Safety data about CAB without PDN are scarce. Corticosteroids present multiple biological effects, which may potentially be either positive, such as those mediated by adrenal androgen and cytokine suppression, or detrimental, such as those associated with the activation of the glucocorticoid receptor (GR) and of the androgen receptor (AR). Furthermore, PDN is a CYP3A4 inducer and can potentially negatively affect CAB clearance. Finally, AR-V7 positivity in circulating tumor cells and retinoblastoma (RB) loss/inactivation have been identified as potential mechanisms of resistance to hormonal and chemotherapy treatments in prostate cancer. For this reason, we also aim to evaluate if CAB activity is related to such biomarkers. Methods: CABACARE (EudraCT 2016-005251-25) is a randomized, phase II, open label, multi-center study comparing CAB at 25 mg/m2 q21 plus daily PDN (10 mg) vs CAB at 25 mg/m2 q21 alone in mCRPC pts progressed during or after DOC treatment. The study is designed to test non inferiority in terms of PFS, according PCWG-2, of CAB alone vs CAB plus PDN assuming that the two arms are equally effective (non-inferiority HR = 1.4). Main secondary objectives are: safety, QoL, pain assessment, overall response rate (ORR), PSA response, time to PSA progression, Time to radiological progression; OS; time to skeletal related events . The influence of AR-V7 and RB status measured in circulating epithelial cells at baseline on CAB activity will also be evaluated. A total of 35 Italian centers have started / will start recruiting pts in the CABACARE trial. Of the 220 pts required by the trial design, 43 pts have been enrolled since 30th Nov , 2017 until 2nd Oct, 2018 in 10 different Italian Institutions. Clinical trial information: 2016-005251-25.

TPS387 Background: In the TROPIC trial, cabazitaxel (CAB) plus daily prednisone (PDN) was associated with a significant advantage in OS and PFS in docetaxel (DOC)-pretreated patients. Whether daily prednisone may significantly contribute to cabazitaxel efficacy or improve its safety profile is unknown. In the CHARTEED trial, DOC was administered without daily PDN with no concerns about the lack of efficacy or greater toxicity. Safety data about CAB without PDN are missing. Corticosteroids present multiple biological effects, which may potentially be either positive, such as those mediated by adrenal androgen and cytokine suppression, or detrimental, such as those associated with the activation of the glucocorticoid receptor (GR) and of the androgen receptor (AR). Furthermore, PDN is a CYP3A4 inducer and can potentially negatively affect cabazitaxel clearance. Finally, AR-V7 positivity in circulating tumor cells and retinoblastoma (RB) loss/inactivation have been identified as potential mechanisms of resistance to hormonal and chemotherapy treatments in prostate cancer. For this reason, we also aim to evaluate if CAB activity is related to such biomarkers. Methods: CABACARE is a randomized, phase II, open label, multi center study comparing CAB at 25 mg/m2 q21 plus daily PDN (10 mg) vs CAB at 25 mg/m2 q21 alone in mCRPC pts progressed during or after DOC treatment. The study is designed to test non inferiority in terms of PFS, according PCWG-2, of CAB alone vs CAB plus PDN assuming that the two arms are equally effective. Each arm will enroll 110 pts. Main secondary objectives are: safety, QoL, pain assessment, overall response rate (ORR), PSA response, time to PSA progression, Time to radiological progression; OS; time to skeletal related events (SRE). The influence of Arv7 and RB status on CAB activity will also be evaluated. Clinical trial information: 2016-005251-25.

e16503 Background: Statins have been associated with favorable effects in various solid malignancies. In prostate cancer, statins may synergize with novel anti-androgen agents enzalutamide and abiraterone via pharmacokinetic interactions and by decreasing substrate availability for androgen de-novo biosynthesis. Methods: Medical records of patients with metastatic castration-resistant prostate cancer (mCRPC) between September, 2011 and August, 2016 were reviewed at multiple participating centers. Results: 187 men received abiraterone, while 129 received enzalutamide. Patients treated with enzalutamide had a more advanced disease, with a median overall survival (OS) of 7.8 vs. 18 months in the abiraterone cohort. In the abiraterone cohort, statin use was a statistically significant prognostic factor for longer OS (HR = 0.40, 95% CI = 0.27 to 0.59, p < 0.001) and statin users vs. non users had greater 30% PSA declines rates at 12 wks(77.9 vs. 52.9%, p < .01) In the enzalutamide cohort, statin use was not prognostic for survival or PSA declines. Conclusions: Our study suggests a prognostic effect of statins plus abiraterone but not enzalutamide for mCRPC. The mechanism of this interaction warrants elucidation but may include enhancing the anti-tumor activity of abiraterone as well as cardioprotective effects. [Table: see text]

386 Background: Trials of salvage therapy for advanced UC have required prior platinum-based therapy. This practice requires scrutiny since non-platinum-based first-line therapy may be offered to cisplatin-ineligible patients (pts). We examined the impact of prior exposure to first-line platinum vs. non-platinum based chemotherapy on overall survival (OS) with salvage systemic chemotherapy. Methods: Data of pts receiving salvage systemic chemotherapy were collected retrospectively or from trials. Data on prior first-line platinum exposure were required in addition to the known prognostic factors: treatment free interval, hemoglobin, performance status, albumin and liver metastasis status. Cox proportional hazards regression was used to evaluate their association with OS after accounting for salvage therapy with single agent chemotherapy or combination chemotherapy. Results: Data was obtained from 455 pts exposed to prior platinum and 37 pts not exposed to prior platinum. In the group exposed to prior platinum, salvage therapy consisted of a single agent taxane (n = 184) and taxane containing combination chemotherapy (n = 271). In the group not exposed to prior platinum, salvage therapy consisted of single agent taxane or vinflunine (n = 20), single agent 5-fluorouracil (n = 1), taxane containing combination chemotherapy (n = 12), carboplatin-based combinations (n = 2) and cisplatin-based combinations (n = 2). The median OS for the prior platinum group was 7.8 (95% CI: 7.0, 8.1) months (mo), and for the prior non-platinum group was 9.0 (6.0, 11.0) mo (p = 0.50). In a multivariable analysis including major prognostic factors and after controlling for single agent or combination salvage chemotherapy, prior platinum vs. no prior platinum exposure conferred no independent impact on OS (HR 1.10 [0.75, 1.64], p = 0.62). Conclusions: Prior platinum vs. non-platinum based chemotherapy did not confer a prognostic impact on OS after accounting for major prognostic factors in pts receiving salvage systemic chemotherapy for advanced UC. Lack of exposure to prior platinum should not disqualify pts from inclusion in trials of salvage therapy after accounting for the 5 known prognostic factors.

335 Background: Perioperative cisplatin based chemotherapy (PCBC) is a standard of care in the management of muscle invasive urothelial carcinoma (UC). Cisplatin based (C) therapy also represents the historical first line treatment of metastatic disease. There is however no data to guide the optimal choice of first line chemotherapy regimen – C re-treatment vs other second-line or non cisplatin regimens (NC) –in UC patients who relapse after receiving PCBC. This multicenter retrospective study compares C vs NC first line treatment on progression-free survival (PFS) for patients (pts) with advanced UC after PCBC and cystectomy. Methods: Data were collected for patients who received various first-line chemotherapies for advanced UC following previous PCBC therapy. Cox proportional hazards models were used to investigate the prognostic ability of type of peri-operative / first-line chemotherapy, visceral metastasis, ECOG status, time from prior chemotherapy (TFPC), anemia, leukocytosis and albumin on PFS. Results: Data were available for 145 pts from 12 centers. The mean age was 62 years, 113 (77.9%) were men and ECOG-PS was 0 or >0 in 74 (51.0%) and 61 (42.0%) patients. Ninety-one (62.8%) pts received C first line, the median number of cycles was 4 (range 1-17) and the median TFPC was 6.2 months (range 1-154). Median overall survival was 86 weeks (95% CI 70-106) and median PFS was 24 (95% CI 18-27) weeks. Time from perioperative chemotherapy (TFPC) (>52 weeks vs ≤52 weeks; HR 0.63 p=0.027) and ECOG-PS at first line (1+ vs 0; HR 1.73 p=0.010), were prognostic of PFS. No significant effect was noted for C vs NC first line (p=0.70); however, among patients with TFPC >52 weeks, patients with NC had worse PFS (median 4.6 months, 95% CI 1.8-12.2) than those who received C (median 8.1, 95% CI 3.2-16.3). Conclusions: There is no evidence to suggest overall superiority of C vs NC based first line chemotherapy or a second-line regimen in patients with advanced UC who received prior PCBC. However, those with TFPC >52 weeks should probably receive C first line chemotherapy given better PFS with C.

225 Background: Cabazitaxel-based chemotherapy provides a survival benefit after docetaxel failure in patients with prostate cancer. Grade 3-4 neutropenia and febrile neutropenia were relatively frequent in the registrative trial, but their incidence in clinical practice is likely to be lower, as shown by data collected in the Expanded Access Program (EAP). While cumulative doses of docetaxel are associated to neuropathy, the effect of cumulative doses of cabazitaxel is unknown. In this study, we assessed 'per cycle' incidence and predictors of toxicity in the Italian cohort of the EAP, with a focus on the effect of cumulative doses of cabazitaxel. Methods: The study population consisted of 218 Italian patients enrolled in the cabazitaxel EAP. The influence of selected variables on the most relevant side effects identified was assessed using a Generalised Estimating Equations (GEE) model at univariate and multivariate analysis. Multivariate logistic regression analysis was performed using a backward selection procedure. Variables with a p value ⩽0.1 were kept in the final model. Results: Per cycle incidence of grade 3-4 neutropenia was 8.7%, while febrile neutropenia occurred only in 0.9% of cycles and was an early event, occurring during the first three cycles only. Multivariate logistic regression analysis showed that the odds of having grade 3 – 4 neutropenia, febrile neutropenia and anemia were statistically significantly reduced by 10, 48 and 7%, respectively, every 10 mg/m2 increase of total prior dose of cabazitaxel. Interestingly, a body surface area > 2 m2 was associated to increased odds of having grade 3-4 neutropenia. In this regard, it must be noted that all patients with body surface area > 2 m2 had their total dose capped to 50 mg, with a mean (95% CI) and median (IQR) dose reduction of 7.1 (7.58-6.69) and 5.9 (2.76-10.27) % with respect to planned dose. Conclusions: Cumulative doses of cabazitaxel are associated to decreased risk of bone marrow toxicity. Patients with body surface area >2 m2 are at increased risk of bone marrow toxicity and dose capping should be considered. These data indicate that cabazitaxel should not be arbitrarily suspended because of concerns of cumulative toxicity.

e15139 Background: No effective treatments for patients with advanced HCC who are intolerant to sorafenib or who have progressed during sorafenib are available. Several studies suggest a relationsh...

7528 Background: Thymic epithelial tumors (TETs) are rare malignancies, with an estimated incidence of about 3 cases per 100,000 inhabitants. No standard treatment is available for recurrent diseas...

e18536 Background: Thymic epithelial tumors (TET) are a rare disease. Once loco-regional treatments have failed, platinum-based chemotherapy is employed to prolong survival and palliate symptoms. In November 2005, we started prospective multi-center trial to test capecitabine-gemcitabine in pretreated TET. Mature results are awaited. We here retrospectively review all patients with TET treated at our Institution with this schedule. Methods: Patients with pathologically confirmed TET receiving at least one cycle of capecitabine-gemcitabine were included in this analysis. Descriptive statistics and frequency counts were used to summarize characteristics of the study population. Median numbers were presented with interquartile ranges. Results: Twenty-three patients were included in this single-center analysis. Six patients had a thymic carcinoma, while three, eight, two and four patients had a B1, B2, B2/B3 and B3 TET, respectively. Median age was 52 years (47-58).Eleven patients were female. Gemcitabine was delivered at the dose of 800-1,000 mg/m2 by 30-minute infusion on days 1 and 8 every 3 weeks along with oral capecitabine at the dose of 500-650 mg/m2 twice daily on days 1 to 14. Fourteen patients had an ECOG performance status of 0, one of 2, the remaining of 1. Seven patients had an IV a tumor, while the remaining had a IVb tumor. All patients, except for three for whom capecitabine-gemcitabine was the first line of therapy, had received a platinum-based regimen. Only one patient was primary refractory, while a complete response was obtained in 2 patients, a partial response in four patients, and the remaining had stable disease. Median PFS was 7 months (range, 4-9). Median survival was 12 months (6-20). Treatment was well tolerated. Twelve patients showed grade 3/4 toxicity, of whom two patients showed severe anemia, six severe neutropenia, four severe thrombocytopenia, two severe diarrhea and one severe fatigue. Conclusions: In this retrospective analysis, gemcitabine-capecitabine was confirmed to have a high activity in TET. Mature results from the ongoing multicenter trial are awaited.

e21500 Background: Classic Kaposi Sarcoma (CKS) is a rare and mild form of the disease that primarily affects men, older than 50 years in the endemic areas. Iatrogenic KS (IKS) is associated with the use of steroids, immunosuppressive agents in patients with autoimmune diseases, inflammatory disorders, or organ transplantation. We have conducted a retrospective analysis from January 2008 to December 2012 for CKS and IKS to evaluated outcomes and potential prognostic factors in this rare disease. Methods: Patients with histologically proven KS lesions of the skin and negative HIV-1/2 were enrolled. In some cases diagnosis was completed by immunohistochemical tests for HHV-8 staining. Eligible patients received different systemic chemotherapy for disease at stage IIb and in all variants of stage III and IV, according Mediterranean KS staging. Results: 32 cases of non-AIDS KS were identified in this study. Mean age at diagnosis of the group was 70 year-old. Approximate male/female ratio was 2:1. 78.2% of cases was classic KS. All patients received systemic chemotherapy containing one of this agent: alkaloid of vinca, taxane, pegylated lyposomial doxorubicin. Ten patients (31.5%) experienced a partial response, a complete response was achieved in 4 patients (12.4%) and stability in 16 cases (50%). Two patients (6.2%) developed multiple local recurrences. PFS was 11.7 months while OS resulted 28.5 months. At multivariate analysis nodular lesions were related to lower PFS compared to macular lesions (HR: 2,5817, 95% CI 1,2911 to 5,1624; p: 0,0049), and HHV8 status (positive vs. negative) had a statistically significant correlation with a worse response to treatment (HR: 5,0289 95% CI 1,6540 to 15,2901; p: 0,0046). Conclusions: Classic and iatrogenic KS patients appears less aggressive, mostly limited to the skin and well-responsive on local or systemic therapeutic strategies. Our data show as positivity to HHV8 and nodular lesions correlate with a worse response to treatment.

7091 Background: Study supported by Agenzia Italiana del Farmaco(AIFA code: FARM6HJ7CA). Thymic epithelial tumors (TETs) are rare tumors of the mediastinum, with an estimated incidence of about 3 c...

378 Background: Vascular endothelial growth factor receptor–tyrosine kinase inhibitors (VEGFr-TKIs) sunitinib (SU) and sorafenib (SO) are approved for first- and second-line (after cytokines) use in metastatic renal cell carcinoma (mRCC). Because most patients progress after first-line VEGFr-TKI, the need for an effective second-line treatment is compelling. Although SO is frequently considered after SU failure, no randomized controlled trials have established clinical benefit in this scenario. Results from the RECORD-1 phase III trial suggest that second-line everolimus (EVE) therapy leads to improved overall survival (OS) vs. placebo. No trial data exist comparing treatment outcomes for EVE vs SO in the second-line setting. Thus, the current analysis provides a robust estimate from an indirect comparison examining the OS benefit of EVE and SO as second-line treatment options after SU failure. Methods: The single-arm SO study was selected as a basis by which to match an EVE SU-refractory subpopulation of the RECORD-1 trial. Patients were limited to those with clear cell histology. An adjusted matching approach was taken in which 1,000 repeated random samples matched to the SO population on risk score distribution were produced. These data were used to generate a distribution of survival outcomes and infer a 95% CI around the mean of all sampled median OS estimates. Results: After adjusted matching, the estimated median OS benefit, based on SO patients with clear cell histology (n = 45) and 1000 random samples of n = 41 from the 127 SU-refractory EVE patients, was 82 weeks (95% CI: 78, 86) and 32 weeks (95% CI: 22, 64) for EVE and SO, respectively. Conclusions: These indirect comparison results suggest that SU-refractory mRCC patients treated with EVE may experience significantly improved OS outcomes compared with patients treated with SO. [Table: see text]