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Background: Real world data have the potential to demonstrate the applicability of the results of randomized studies in the general population. SUPER trial was conducted in order to assess the activity, the efficacy and the safety of the combination of pertuzumab, trastuzumab and chemotherapy in clinical practice.Material and methods: Patients diagnosed with HER2 positive metastatic breast cancer (mBC) and treated with pertuzumab, trastuzumab and chemotherapy were accrued at 18 italian hospitals. Data were retrospectively collected in the time frame between pertuzumab availability in clinical practice and study approval in 2016, and prospectively collected thereafter. Results: Overall 342 HER2 positive mBC were accrued. 172 patients had relapsed disease and 56.4% of them received neo/adjuvant trastuzumab. 205 patients received docetaxel. Objective response rate was 76.3% (95%CI: 71.4–80.7). Median progression free survival (PFS) and overall survival (OS) were 24.3 months (95% CI: 20.0–28.9) and 70.2 months (95% CI: 61.4–79.0) respectively. Triple positive patients treated with endocrine therapy in addition to pertuzumab and trastuzumab maintenance had a significant longer PFS and OS than patients who did not. mPFS was 31.2 months and 13 months respectively (HR=0.47; 95% CI: 0.33–0.66; pConclusions: SUPER suggests that results of first-line treatment with pertuzumab, trastuzumab and chemotherapy in unselected patients are consistent with findings from CLEOPATRA trial.Moreover, as expected from real world evidence, new insights have emerged.

Background To reduce the overall exposure to dexamethasone (DEX) in patients receiving cisplatin‐based chemotherapy, we evaluated the noninferiority of DEX on day 1, with or without low‐dose DEX on days 2 and 3, combined with an oral fixed‐dose combination of netupitant and palonosetron (NEPA), compared with the guideline‐consistent use of 4‐day DEX. Patients and Methods In this open‐label, multicenter study, chemotherapy‐naïve patients undergoing high‐dose cisplatin (≥70 mg/m2), were given NEPA and DEX (12 mg) on day 1 and randomized (1:1:1 ratio) to receive either (a) no further DEX (DEX1), (b) oral DEX (4 mg daily) on days 2–3 (DEX3), or (c) DEX (4 mg twice daily) on days 2–4 (DEX4). The primary efficacy endpoint was complete response (CR: no emesis and no rescue medication) during the 5‐day overall phase. The noninferiority margin was set at −15% difference (DEX1 or DEX3 minus DEX4). Secondary efficacy endpoints included complete protection (CP: CR and none or mild nausea). Results Two‐hundred twenty‐eight patients, 76 in each arm, were assessable. Noninferiority was met for both DEX‐sparing regimens and the reference arm, with overall phase CR rates of 76.3% in each of the DEX1 and DEX3 arms and 75.0% in the DEX4 arm (95% confidence interval, −12.3% to 15% for each comparison). During the overall phase, CP rates were similar between groups. Conclusion A simplified regimen of NEPA plus single‐dose DEX offers comparable chemotherapy‐induced nausea and vomiting prevention throughout 5 days post‐chemotherapy with the advantage of sparing patients additional doses of DEX in the high–emetic‐risk setting of cisplatin‐based chemotherapy. Implications for Practice Dexamethasone (DEX) has traditionally played an integral role in the management of chemotherapy‐induced emesis. Although generally considered safe, even short‐term DEX use is associated with various side effects, and some evidence suggests that concurrent steroids may reduce the efficacy of immunotherapies. This study demonstrates comparable antiemetic control during the 5 days post‐chemotherapy with a simplified regimen of netupitant/palonosetron plus single‐dose DEX versus the standard 4‐day DEX reference treatment in high‐dose cisplatin. This represents a clinically relevant achievement as it not only simplifies antiemetic prophylaxis but also offers an opportunity to appropriately use in patients where caution with corticosteroid use is advised., This study was designed to test whether two different dexamethasone‐sparing regimens, when administered with NEPA, might provide the opportunity to reduce the total corticosteroid dose while maintaining the same degree of chemotherapy‐induced nausea and vomiting control in patients undergoing cisplatin‐based chemotherapy.

Background:The CDK4/6 inhibitor palbociclib combined with endocrine therapy (ET) has proven to prolong progression-free survival (PFS) in women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (MBC). Few data are available regarding the efficacy of such a regimen outside the clinical trials.Patients and methods:This is a multicentre prospective real-world experience aimed at verifying the outcome of palbociclib plus ET in an unselected population of MBC patients. The primary aim was the clinical benefit rate (CBR); secondary aims were the median PFS, overall survival (OS) and safety. Patients received palbociclib plus letrozole 2.5 mg (cohort A) or fulvestrant 500 mg (cohort B).Results:In total, 191 patients (92 in cohort A, 99 in cohort B) were enrolled and treated, and 182 were evaluable for the analysis. Median age was 62 years (range 47–79); 54% had visceral involvement; 28% of patients had previously performed one treatment line (including chemotherapy and ET), 22.6% two lines and 15.9% three. An overall response rate of 34.6% was observed with 11 (6.0%) complete responses and 52 (28.6%) partial responses. Stable disease was achieved by 78 patients (42.9%) with an overall CBR of 59.8%. At a median follow-up of 24 months (range 6–32), median PFS was 13 months without significant differences between the cohorts. When analysed according to treatment line, PFS values were significantly prolonged when palbociclib-based therapy was administered as first-line treatment (14.0 months), to decrease progressively in second and subsequent lines (11.7 and 6.7 months, respectively). Median OS was 25 months, ranging from 28.0 months in 1st line to 18.0 and 13.0 months in 2nd and subsequent lines, respectively.Conclusions:Our data indicate that palbociclib plus ET is active and safe in HR+/HER2− MBC, also suggesting a better performance of the combinations in earlier treatment lines.

Introduction Metastatic breast cancer (MBC) is a life-threatening disease, and although some data suggest a trend in survival improvement, it has not yet been unequivocally demonstrated. This study aimed to evaluate the overall survival (OS) of MBC patients, assessing its correlation with prognostic factors. Patients and Methods COSMO (Checking Overall Survival in a MBC Observational study) is an Italian longitudinal retrospective multicenter study that enrolled patients with MBC diagnosed between 2000 and 2008. The primary objective was to detect a temporal difference in OS; the secondary objective was to identify prognostic factors as causal factors of the temporal variation in OS. Results A total of 3721 of 3930 patients from 31 centers were distributed in 3 periods: 886 (23.8%), 1302 (35.0%), and 1533 (41.2%) in 2000-2002, 2003-2005, and 2006-2008, respectively. With a median follow-up of 9.3 years, median OS was 2.8 years (95% confidence interval, 2.6-2.9). No difference in OS was found in the 3 cohorts (P for trend = .563). The worst prognosis was observed for patients with triple-negative MBC (OS, 1.5 years) and for those with central nervous system metastases (1.7 years); the best prognosis was observed in those with bone metastases or nonvisceral disease (3.4 and 3.2 years, respectively) and in patients with a disease-free interval, defined as the time between resection of the primary malignancy and diagnosis of MBC, of > 2 years (3 years). Conclusions The COSMO study found improvement in OS between 2000 and 2008. Molecular subtype remained the strongest prognostic factor, and the role of other prognostic factors was confirmed, in particular disease-free interval, site of metastasis, and age.

Background NEPA is an oral fixed-dose combination of netupitant, a new highly selective neurokinin-1 receptor antagonist, and palonosetron. This study was conducted to evaluate whether the efficacy of NEPA against chemotherapy-induced nausea and vomiting (CINV) in cycle 1 would be maintained over subsequent chemotherapy cycles in breast cancer patients receiving adjuvant anthracycline plus cyclophosphamide (AC). The study also describes the relationship between efficacy on day 1 through 5 (overall period) and control of CINV on day 6 through 21 (very late period) in each cycle. Methods In this multicentre, phase II study, patients received both NEPA and dexamethasone (12 mg intravenously) just before chemotherapy. The primary efficacy endpoint was overall complete response (CR; no emesis and no rescue medication use) in cycle 1. Sustained efficacy was evaluated during the subsequent cycles by calculating the rate of CR in cycles 2–4 and by assessing the probability of sustained CR over multiple cycles. The impact of both overall CR and risk factors for CINV on the control of very late events (vomiting and moderate-to-severe nausea) were also examined. Results Of the 149 patients enrolled in the study, 139 were evaluable for a total of 552 cycles; 97.8% completed all 4 cycles. The proportion of patients with an overall CR was 70.5% (90% CI, 64.1 to 76.9) in cycle 1, and this was maintained in subsequent cycles. The cumulative percentage of patients with a sustained CR over 4 cycles was 53%. NEPA was well tolerated across cycles. In each cycle, patients with CR experienced a significantly better control of very late CINV events than those who experienced no CR. Among the patients with CR, the only predictor for increased likelihood of developing very late CINV was pre-chemotherapy (anticipatory) nausea (adjusted odds ratio = 0.65–0.50 for no CINV events on cycles 3 and 4). Conclusion The high anti-emetic efficacy seen with the NEPA regimen in the first cycle was maintained over multiple cycles of adjuvant AC for breast cancer. Preliminary evidence also suggests that patients achieving a CR during the overall period gain high protection even against very late CINV events in each chemotherapy cycle. Trial registration This trial was retrospectively registered at Clinicaltrials.gov identifier (NCT03862144) on 05/Mar/2019.

BACKGROUND - Metastatic breast cancer (MBC) is a life-threatening disease. It is important to provide data about real-life MBC patients (pts) to understand the current prognostic factors. The aim of the present observational study, named COSMO (Checking Overall Survival in a MBC Observational study) is to describe the overall survival (OS) in a large cohort of MBC pts, assessing its correlation with specific prognostic factors (demographic, clinic, pathologic and biological). PATIENTS AND METHODS - The COSMO study is a multicenter, retrospective, cohort study, developed throughout the collaboration of 31 Italian oncological centers. Data about pts diagnosed as metastatic from 01/01/2000 to 31/12/2008, were collected. The association between molecular subtypes, metastatic sites, disease free interval (DFI) and OS were assessed. Pts were classified in three subgroups, based on the biological characteristics of their tumor: luminal, HER2-positive (regardless of hormone receptor) and triple negative (TN). Metastatic sites were categorized as visceral versus non-visceral disease, only bone and central nervous system (CNS) metastases. DFI was calculated from diagnosis to first relapse only for M0 pts. RESULTS - Of 3931 MBC pts enrolled in the study, 3720 were evaluable, with a median age of 61 years (interquartile range, IQR, 51-71). 1804 (62,1%) pts had a luminal disease, 691 (23,8%) HER2-positive, 410 (14.1%) TN. Median DFI was 3.2 years (IQR 1.7- 6.0). Regarding metastatic sites, pts with visceral disease were 2332 (63%); 826 (22,2%) pts had bone isolated metastases; in 306 (8,3%) pts, CNS metastases were reported. With a median follow up of 9 years (IQR 5.7-11.0) and 3098 (83.3%) recorded events, we founded a median OS of 2.8 years (95%CI: 2.7-2.9) years. OS was strictly depending from molecular subtypes with a better prognosis for HER2-positive versus luminal and TN MBC pts, median OS of 3.1 (95%CI 2.8-3.4), 3.0 (95%CI: 2.9-3.1) and 1.5 (95%CI: 1.3-1.7) years respectively (p-value2 years show a median OS of 3 years (95% CI: 2.9 – 3.2), while those with DFI CONCLUSIONS - Molecular subtype is crucial for prognosis: HER2-positive subtype has the best prognosis, while TN subtype has the shorter OS. Having a longer DFI from diagnosis (>2 years) correlate with a better prognosis. Our study confirm that sites of metastasis affects outcome: visceral involvement correlates with poor prognosis and, particularly, pts with brain metastasis represent the worst subgroup, while pts with solely bone disease have the best prognosis. The COSMO study provides a view on the Italian landscape of MBC between 2000 and 2008, adding new insights about pts prognosis. Citation Format: La Verde N, Collovà E, Blasi L, Pinotti G, Bernardo A, Bonotto M, Garrone O, Brunello A, Cavazzini MG, Bareggi C, Prochilo T, Porcu L, Moretti A, Barni S, On Behalf of COSMO Study Group. Overall survival in metastatic breast cancer patients in the third millennium: Results of an Italian study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-14-04.

Background: Around 20% of breast cancers (BC) are HER-2+. Trastuzumab (T) has dramatically changed the outcome of HER-2+ BC patients (pts), both in early and in advanced settings. The combination of Pertuzumab (P) plus T and docetaxel, used as first-line treatment for HER-2+ metastatic BC (MBC) in the phase III CLEOPATRA study, significantly prolonged progression free survival (PFS) and overall survival (OS). In order to verify the results of the Cleopatra trial in unselected pts, we performed a multicenter, retrospective-prospective, observational study, in HER-2+ MBC pts candidate to receive first line therapy with P plus T plus taxanes. Methods: We analyze the outcome of all HER-2+ MBC pts treated with P+T and taxanes, as first line therapy since the availability of P in Italy (2013), at 13 general and university hospitals. Results: Until June 6th data from 217 HER-2+ MBC pts were recorded. Main pts' characteristics were: median age 54 y (28-80), median ECOG PS 0 (0-2), hormonal receptor positive 152 pts (70%), 60 pts (27.6%) received neo/adjuvant chemotherapy (CT) + T and 75 pts (34.5%) adjuvant endocrine therapy. Most common metastatic sites: bone 121 pts (55.7%), liver 85 pts (39.2%), lung 61 pts (28.1%), soft tissues 133 pts (61.3%); 8 pts had CNS involvement. Seventy-eight pts (35.9%) had bone and/or soft tissues disease only; 108 pts (49.7%) had metastatic disease on presentation. Median number of metastatic sites was 3 (1-8). 144 pts (66.3%) and 72 pts (33.2%) received docetaxel (D) and paclitaxel (P) respectively. Median number of CT cycles was 6 for both drugs (D range 1-13; P range 1-18). Up to now 23 pts are still on CT and 86 on maintenance; ORR in evaluated pts (189) is 80.9% (47 and 106 pts obtained CR and PR respectively), 11 pts experienced PD during CT; 113 pts (58.2%) received endocrine therapy during maintenance.Median PFS is 14.7+ months (0.3+ - 53.2+). Most common adverse events are reported in table 1 Table 1Adverse EventAll grades N (%)Grade 3-4 N (%)Leukopenia39 (18)10 (4.6)Neutropenia42 (19.3)16 (7.3)Anemia50 (23)2 (0.9)Febrile Neutropenia7 (3.2) Diarrhea103 (47.4)10 (4.6)Asthenia127 (58.5)5 (2.3)Peripheral Neuropathy80 (36.8)3 (1.3)Stomatitis67 (30.8)2 (0.9) Nail changes, nausea, alopecia, rash and arthro-myalgia were also reported. Three pts interrupted CT due to symptomatic drop of left ventricular ejection fraction (LVEF); 2 pts interrupted maintenance P due to rash and dyspnea respectively, 16 stopped P and T due to drop in LVEF, 1 due to occurrence of ALL and 1 refused to continue. Conclusions: Our preliminary results highlight the activity and safety of the combination of CT plus P and T in unselected HER-2+ MBC patients. The study is ongoing and updated results will be presented. Citation Format: Garrone O, D'Onofrio L, Blondeaux E, Bertolini I, Giarratano T, Beano A, Saggia C, Cazzaniga M, LaVerde N, Collovà E, Milani A, De Conciliis E, Coltelli L, Airoldi M, Del Mastro L, Cursano MC, Michelotti A, Vandone AM, Guarneri V, Donadio M, Riva F, Nuzzo A, Merlano MC. Moving from the CLEOPATRA study to real life: Preliminary results from the G.O.N.O. SUPER trial [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-21-29.

Currently there are no reliable biomarkers to predict outcome of exemestane treatment. We designed a prospective study to investigate whether constitutive genetic background might affect response to therapy. In a population of 302 advanced breast cancer patients treated with exemestane we showed that a 5-polymorphism-based genetic score could be used to identify patients with different risks of progression and death.Introduction: Approximately 50% of locally advanced or metastatic breast cancer (MBC) patients treated with first-line exemestane do not show objective response and currently there are no reliable biomarkers to predict the outcome of patients using this therapy. The constitutive genetic background might be responsible for differences in the outcome of exemestane-treated patients. We designed a prospective study to investigate the role of germ line polymorphisms as biomarkers of survival. Patients and Methods: Three hundred two locally advanced or MBC patients treated with first-line exemestane were genotyped for 74 germ line polymorphisms in 39 candidate genes involved in drug activity, hormone balance, DNA replication and repair, and cell signaling pathways. Associations with progression-free survival (PFS) and overall survival (OS) were tested with multivariate Cox regression. Bootstrap resampling was used as an internal assessment of results reproducibility. Results: Cytochrome P450 19A1-rs10046TC/CC, solute carrier organic anion transporter 1B1-rs4149056TT, adenosine triphosphate binding cassette subfamily G member 2-rs2046134GG, fibroblast growth factor receptor-4-rs351855TT, and X-ray repair cross complementing 3-rs861539TT were significantly associated with PFS and then combined into a risk score (0-1, 2, 3, or 4-6 risk points). Patients with the highest risk score (4-6 risk points) compared with ones with the lowest score (0-1 risk points) had a median PFS of 10 months versus 26.3 months (adjusted hazard ratio [AdjHR], 3.12 [95% confidence interval (CI), 2.18-4.48]; P < .001) and a median OS of 38.9 months versus 63.0 months (AdjHR, 2.41 [95% CI, 1.22-4.79], P = .012), respectively. Conclusion: In this study we defined a score including 5 polymorphisms to stratify patients for PFS and OS. This score, if validated, might be translated to personalize locally advanced or MBC patient treatment and management.

Metronomic chemotherapy (mCT), a frequent administration of low-dose chemotherapy, allows prolonged treatment duration and minimizes the toxicity of standard-dose chemotherapy. mCT has multiple actions against cancer cells including inhibition of angiogenesis and modulation of the immune system. A number of studies lend support to the clinical efficacy of mCT in advanced breast cancer and non-small-cell lung cancer. However, further evidence is necessary to describe the optimal use of mCT and to identify suitable patients. Oral vinorelbine has emerged as a promising metronomic treatment in patients with metastatic breast cancer and non-small-cell lung cancer and is the only orally available microtubule-targeting agent. This paper reviews current evidence on metronomic oral vinorelbine, discusses its management and defines a suitable patient profile on the basis of a workshop of Italian experts.

BACKGROUND: Patients with small-cell lung cancer (SCLC) that progress after first-line chemotherapy have a poor prognosis and the evidence of a benefit from second-line (SL) chemotherapy is limited. Patients relapsing or progressing more than 90 days after completion of first-line treatment are considered platinum sensitive and may be rechallenged with platinum-based chemotherapy. Topotecan is approved as SL treatment independent of time to progression. This retrospective analysis evaluates the clinical outcomes of SCLC patients who received SL chemotherapy after platinum-etoposide chemotherapy. PATIENTS AND METHODS: We retrospectively reviewed 161 patients who received SL chemotherapy for SCLC. Patients were divided into four subgroups by type of SL treatment: (1) platinum-based rechallenge; (2) anthracycline-based regimens; (3) topotecan; (4) other single agents. The endpoints were overall survival (OS), progression-free survival (PFS) and response rate (RR). Survival curves were plotted using the Kaplan-Meier method. The Cox proportional hazard model was used for multivariate analysis to investigate factors influencing survival. RESULTS: The median age was 63. There were 125 males and 36 females. Eastern Cooperative Oncology Group performance status (ECOG-PS) was 0, 1 and 2 in 12.5%, 62.5% and 25% of patients, respectively. Platinum sensitive/platinum resistant/platinum refractory/unknown=121/29/3/8 patients. Median time to SL chemotherapy was 6.9 months. The median PFS from starting second-line treatment was 4.3 months and median OS was 5.8 months. The overall RR was 22.9%. There was a trend toward higher RR (34.5% vs 17.5%, p for trend: 0.06) and OS (9.2 months vs 5.8 months, p=0.08) for patients with sensitive disease who were rechallenged with platinum-based chemotherapy. A multivariate analysis that adjusted for the time to SL treatment showed that a platinum-containing regimen achieves better RR, PFS and OS independently of the time to SL chemotherapy and that response to first-line treatment and PS at SL are the only independent prognostic factors. CONCLUSIONS: The outcome for second-line therapy for SCLC was poor and benefit appeared to be limited to those patients with good PS and rechallenged with platinum-based chemotherapy. Platinum-based rechallenge should be considered as a standard comparator in future randomized controlled trials of SL chemotherapy.

The use of oral anticancer drugs has shown a steady increase. Most patients prefer anticancer oral therapy to intravenous treatment primarily for the convenience of a home-based therapy, although they require that the efficacy of oral therapy must be equivalent and toxicity not superior than those expected with the intravenous treatment. A better patient compliance, drug tolerability, convenience and possible better efficacy for oral therapy as compared to intravenous emerge as the major reasons to use oral anticancer agents among oncologists. Inter- and intra-individual pharmacokinetic variations in the bioavailability of oral anticancer drugs may be more relevant than for intravenous agents. Compliance is particularly important for oral therapy because it determines the dose-intensity of the treatment and ultimately treatment efficacy and toxicity. Patient stands as the most important determinant of compliance. Possible measures for an active and safe administration of oral therapy include a careful preliminary medical evaluation and selection of patients based on possible barriers to an adequate compliance, pharmacologic issues, patient-focused education, an improvement of the accessibility to healthcare service, as well as the development of home-care nursing symptom-focused interventions. Current evidences show similar quality of life profile between oral and intravenous treatments, although anticancer oral therapy seems to be more convenient in terms of administration and reduced time lost for work or other activities. Regarding cost-effectiveness, current evidences are in favor of oral therapy, mainly due to reduced need of visits and/or day in hospital for the administration of the drug and/or the management of adverse events. © 2010 Elsevier Ltd.

e13006Background: Approximately 20% of breast cancers (BC) are HER-2+. Trastuzumab (T) has dramatically changed the outcome, both in early and in advanced settings in HER2+BC. Pertuzumab (P) plus T...

Pegfilgrastim is a covalent conjugate of filgrastim and polyethylene glycol that has proved to be effective in supporting myelopoiesis during chemotherapy. Since very limited information is available on the biological effects of pegfilgrastim on neutrophils exposed to chemotherapy, we analyzed the following parameters in neutrophils of patients undergoing dose-dense chemotherapy for breast cancer: apoptosis, by a TUNEL technique; actin polymerization, using FITC-labeled phalloidin, and alkaline phosphatase activity by cytochemistry. Peripheral blood buffy coat smears were obtained before starting treatment and immediately before each chemotherapy course. After pegfilgrastim stimulation we observed the following: (1) stability of the absolute neutrophil count for the whole duration of treatment and no infectious events; (2) a reduction in the neutrophil constitutive apoptosis rate in comparison with that observed in control patients treated with standard chemotherapy courses with no growth factor support; (3) persistent abnormalities of actin assembly in neutrophils, indicative of changes in cytoskeletal organization, and (4) a significant increase in the activity of leukocyte alkaline phosphatase, a sensitive marker of the later stages of neutrophil maturation. In conclusion, these results suggest that pegfilgrastim improves the neutrophil functions in patients exposed to chemotherapy by inhibition of constitutive apoptosis, thereby prolonging the survival of these cells.

Aim To assess patient perception toward oral chemotherapy for solid tumors, the Italian Association of Medical Oncology performed a large multi-institutional national survey. Methods A 17-item anonymous questionnaire including 7 general and 10 investigational questions with free-text, single-choice, or multiple-choice answers was administered. Analysis of response distribution according to predefined factors was described by summary measures and conducted by χ2 test and other nonparametric tests. Results From January to June 2010, 581 patients completed the questionnaire; data of 404 patients constituted the final study sample. Three groups could be distinguished according to treatment: IV chemotherapy (IV group, n = 313), oral chemotherapy (oral group, n = 48), or combined therapy (combined group, n = 43). Thirty-one (72%) patients in the combined group and 187 (60%) in the IV group expressed preference for oral therapy (p = 0.028). Limitations in family and work commitment were more frequently perceived by patients on IV than oral chemotherapy (147 (47%) vs 14 (29%) patients, pConclusions We observed a propensity from the patient perspective in favor of oral chemotherapy that was considered to have a lower impact on family and work commitments than IV chemotherapy. The treatment that patients were taking when the questionnaire was administered likely influenced their perception and related results.

We conducted a large, multicenter, retrospective survey aimed to explore the impact of tumor bone involvement in Non-Small Cell Lung Cancer.Data on clinical-pathology, skeletal outcomes and bone-directed therapies for 661 deceased patients with evidence of bone metastasis were collected and statistically analyzed. Bone metastases were evident at diagnosis in 57.5% of patients. In the remaining cases median time to bone metastases appearance was 9 months. Biphosphonates were administered in 59.6% of patients. Skeletal-related events were experienced by 57.7% of patients; the most common was the need for radiotherapy. Median time to first skeletal-related event was 6 months. Median survival after bone metastases diagnosis was 9.5 months and after the first skeletal-related event was 7 months. We created a score based on four factors used to predict the overall survival from the diagnosis of bone metastases: age >65 years, non-adenocarcinoma histology, ECOG Performance Status >2, concomitant presence of visceral metastases at the bone metastases diagnosis. The presence of more than two of these factors is associated with a worse prognosis.This study demonstrates that patients affected by Non-Small Cell Lung Cancer with bone metastases represent a heterogeneous population in terms of risk of skeletal events and survival.

ABSTRACT Background: Increasing age of first pregnancy among Italian women with premenopausal breast cancer makes adjuvant hormonal therapy a hot topic, justifying a survey on the therapeutic approach of Italian oncologists. Materials & methods: From April to July 2012, an 11-item electronic questionnaire was submitted to Italian oncologists and 611 out of 974 invited filled questionnaires were collected from all over Italy. Results: In total, 97.7% of patients aged

e12510 Background: Approximately 20% of breast cancers (BC) are HER-2+. Trastuzumab (T) has substantially improved the outcome, both in early and in advanced settings, in HER-2+BC. Pertuzumab (P), combined with T and taxanes, ameliorated progression free survival (PFS) and overall survival (OS) in the phase III CLEOPATRA study. In order to verify the results of the trial in unselected patients (pts), we performed a multicenter, retrospective-prospective, observational study, in HER-2+ metastatic BC (MBC) pts. Methods: We analyze the outcome of all HER-2+ MBC pts treated with P+T and taxanes, as first line therapy since the availability of P in Italy, at 11 general and university hospitals. Results: Up to February 1stdata from 103 HER-2+ MBC pts were recorded. Main pts’ characteristics were: median (M) age 52 y (28-78), m ECOG PS 0 (0-2), ER/PgR positive 68 pts (66%). Most common metastatic sites: liver 51 pts (49.5%), bone 64 pts (62.1%), lung 26 pts (25.2%). Thirty pts (29.1%) had bone and soft tissue disease only; 78 pts (75.7%) had metastatic disease on presentation. m number of metastatic sites was 3 (1-7); 25 pts (24.3%) received neo/adjuvant chemotherapy (CT) + T and 36 pts (34.9%) adjuvant endocrine therapy; 71 pts (69%) and 32 pts (31%) received docetaxel (D) and paclitaxel (P) respectively. m number of CT cycles was 6 for both drugs (D range 3-12; P range 1-18).At the time of the present analysis 12 pts are still on CT and 78 on maintenance; response is available for 91 pts and ORR is 80.2% (22 pts and 51 pts obtained CR and PR respectively), 6 pts experienced PD during CT. Median PFS is 13.9 months (1.5+ - 33.8+).Among hematological toxicities leucopenia (any grade) was recorded in 29 pts (28.1%), g 3 febrile neutropenia in 6 pts (5.8%). No change of left ventricular ejection fraction (LVEF) was recorded during CT; 4 pts interrupted maintenance P due to drop in LVEF and 1 due to rash. Onicopathy, nausea, alopecia, rash and arthro-myalgia were the most common non-hematological toxicities. Conclusions: Our preliminary results highlight the activity and the safety of the combination of CT plus P and T in unselected HER2+ MBC patients. The study is ongoing and updated results will be presented.

BACKGROUND Eribulin is a synthetic analogue of halichondrin B which inhibits microtubule dynamics. It has been approved in Europe for the treatment of locally advanced or metastatic breast cancer (mBC) progressed after at least two chemotherapy regimens for advanced disease. The most common adverse events (AEs) were fatigue, neutropenia and peripheral neuropathy, which occurs with an incidence ranging from 13.9% to 35%. It was severe only in a small proportion of patients, suggesting an individual susceptibility. The neurotoxicity mechanisms associated with microtubulin interfering agents have not been fully defined. Few studies reported an association between some SNPs (Single Nucleotide Polymorphisms) and microtubulin interfering agents-induced neuropathy, mainly taxanes. As the use of Eribulin becomes more widespread, a better knowledge of its safety profile, outside of clinical trials, is warranted. Given that Eribulin toxicity can result in treatment discontinuation, the ability to anticipate which patients will experience severe toxicity could allow for either early intervention or even possibly for prophylactic therapy, or for a better selection of patients eligible for treatment. METHODS This is a multicenter, interventional, single-arm, phase IV study. The primary objective is the evaluation of the safety and tolerability profile of Eribulin in an unselected population of patients with mBC. Secondary objectives are the description of compliance to treatment and efficacy. ENDPOINTS •Incidence, time of onset, severity and duration of all AEs experienced during treatment with Eribulin, especially the most common reported in previous studies but also other possible unexpected toxicities. •Association between a set of selected SNPs and the onset of any grade peripheral neuropathy. Specifically, 15 SNPs located in genes involved in microtubule dynamics or resulted from genome wide association studies, will be analyzed. •Evaluation of quality of life during treatment using validated questionnaires. •Assessment of dose intensity and dose schedule maintenance. •DOT (Duration Of Treatment) and OS (Overall Survival). STATISTICAL METHODS Summary statistics will be used in order to describe patient characteristics. Safety endpoints will be estimated by means of absolute and relative frequencies and associated 95%CI. The relationship between baseline variables and the risk of severe toxicity, as well as the relationship between SNPs and risk of neuropathy will be described by means of contingency tables and their association with outcome will be assessed by χ2 test of Mantel-Haenzel and a logistic regression model. DOT and OS will be described using Kaplan-Meier curves. A sample size of 200 patients will also allow us to get a good fitting for statistical analysis of the relationship between primary endpoint and not more than 10 factors. Regarding the relationship between SNPs and risk of neuropathy it will be feasible to screen for association about 10-15 SNPs, with known prevalence >15%. PRESENT ACCRUAL AND TARGET ACCRUAL 98 of 200 patients were enrolled until 18/05/2016. Target accrual is open for 200 patients. CONTACT INFORMATION Nicla La Verde: nicla.laverde@asst-fbf-sacco.it. Citation Format: La Verde N, Moretti A, Damia G, Paternò E, Santini D, Garrone O, Fabi A, Ciccarese M, Cretella E, Torri V, Generali D, Grasso D, Puglisi F, Collovà E, Roila F, Bertolini A, Barni S, Vici P, Luigi C, Scandurra G, Bramati A, Dazzani MC, Farina G. PAINTER: Evaluation of eribulin tolerability and correlation between a set of polymorphisms and neuropathy in patients with metastatic breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT1-01-05.

BackgroundBone metastasis represents an increasing clinical problem in advanced renal cell carcinoma (RCC) as disease-related survival improves. There are few data on the natural history of bone disease in RCC.Patients and methodsData on clinicopathology, survival, skeletal-related events (SREs), and bone-directed therapies for 398 deceased RCC patients (286 male, 112 female) with evidence of bone metastasis were statistically analyzed.ResultsMedian time to bone metastasis was 25 months for patients without bone metastasis at diagnosis. Median time to diagnosis of bone metastasis by MSKCC risk was 24 months for good, 5 months for intermediate, and 0 months for poor risk. Median number of SREs/patient was one, and 71% of patients experienced at least one SRE. Median times to first, second, and third SRE were 2, 5, and 12 months, respectively. Median survival was 12 months after bone metastasis diagnosis and 10 months after first SRE. Among 181 patients who received zoledronic acid (ZOL), median time to first SRE was significantly prolonged versus control (n = 186) (3 months vs 1 month for control; PConclusionsRCC patients with bone metastasis are at continuous risk of SREs, and in this survey ZOL effectively reduced this risk.

The pemetrexed-cisplatin chemotherapy is standard of care in first-line (FL) treatment of malignant pleural mesothelioma (MPM). The second-line (SL) chemotherapy is considered, but the optimal treatment has not been defined yet. The aim of this study was to evaluate the clinical outcomes of SL-therapy in a series of MPM-patients included in a retrospective multicenter database. Clinical records of MPM-patients who received SL-treatment from 1996 to 2008 were reviewed. Study endpoints were response, overall-survival (OS), and progression-free-survival (PFS) for SL, stratified for patient characteristics, FL-outcomes, and type of SL. Out of 423 patients, 181 with full clinical data were identified. Patients' characteristics: median-age 64 years (range: 36-85); male gender 115 (63.5%); good EORTC-score 109 (60.2%); epithelial histology 135 (74.6%). After FL, 147 (81.2%) patients achieved disease-control (DC) and 45 had a time-to-progression≥12 months (TTP≥12). After SL, 95 patients (52.6%) achieved DC (21 response; 74 stable-disease); median PFS and OS were 4.3 and 8.7 months, respectively. According to multivariate analysis, DC after SL-therapy was significantly related to pemetrexed-based treatment (OR: 2.46; p=0.017) and FL-TTP≥12 (OR: 3.50; p=0.006). PFS was related to younger age (

The aim of this study was to evaluate the effect of dose-dense adjuvant chemotherapy regimens with peg-filgrastim support on the phenotype of peripheral blood leukocytes in breast cancer patients. We evaluated the leukocyte phenotype of 14 patients aged 46-67 years undergoing 4 courses of chemotherapy with either epirubucin/cyclophosphamide (n=7) or 5-fluorouracil/epirubucin/cyclophosphamide (n=7) followed by 4 courses of taxol supported by peg-filgrastim (6 mg) administered 72 h after each chemotherapy course. The overall leukocyte number significantly increased from the first treatment course, while total lymphocytes tended to decrease with a negative peak following the 6th course (p=0.03). B (CD19+, CD20+) and early B lymphocyte subsets (CD20+/CD38+) significantly decreased during treatment (p

The effects of topotecan-based chemotherapy (CT) on peripheral blood lymphocyte (PBL) subsets were evaluated in ovarian cancer patients. Fourteen patients with epithelial ovarian cancer, at the diagnosis or relapsed after platinum-based CT, were treated with: a) topotecan in association with carboplatin and taxanes as first line CT; b) topotecan alone or c) topotecan in association with carboplatin both as second line of treatment after platinum. The phenotype of PBL was determined before starting treatment and immediately before each CT course by flow cytometric analysis. Before starting CT, the absolute number of lymphocytes and the CD2+, CD3+, CD4+ subsets were significantly lower in pre-treated patients and not significantly altered in CT-naive patients with respect to a cohort of 20 healthy donors utilized as control. Lymphocytes co-expressing CD4+/CD8+ were significantly higher in both subgroups of patients than in normal donors. CD4+/CD45RA+ and CD4+/CD45RO+ subsets were significantly decreased in pre-treated patients and normal in CT-naive patients. CD3+/HLA-DR+ T cell population significantly increased in CT-naive patients at baseline. During CT and after its discontinuation, no relevant changes were recorded for both subgroups of patients with respect to the baseline in lymphocyte absolute count, CD2+, CD3+, CD4+, CD4+/CD45RO+ subsets, while CD4+/CD45RA+ subpopulation was significantly decreased in CT-naive patients. CD8+, CD19+, CD20+, CD16+, CD56+, CD2+/CD25+ subsets did not differ statistically comparing to normal donors both at baseline and during CT. The treatment was well tolerated and no patient developed non-neutropenic infection. Topotecan-based therapy does not have a negative impact on PBL in either CT-naive or in pretreated ovarian cancer patients. This information should be considered when utilizing topotecan with other anticancer drugs in the adjuvant setting as well as when dose-intensification of topotecan with stem cell support is planned.

Aim: A growing evidence supports the efficacy and safety of different dosing schedules of nab-paclitaxel (nab-P) through several treatment lines in MBC, also in taxane-pretreated patients (pts). We report the final results of a multicenter experience with single-agent nab-P as 2nd and further chemotherapy (CT) in MBC, focusing on potential predictive and/or prognostic factors for treatment response and disease outcome. Methods: From February 2011, 150 consecutive MBC pts were treated at 8 Italian Institutions, 85 (cohort A) with the 260mg/m2 q3w schedule (46 in 2nd line, 21 in 3rd and 18 in ≥ 4th) and 65 (cohort B) with the 125 mg/m2 (20 in 2nd line, 10 in 3rd and 35 in ≥ 4th). Visceral involvement: 72%; ≥3 metastatic sites: 60%; median DFI ≤24 months: 35%; taxane-based CT in the adjuvant or metastatic setting: 68% and 65%, respectively. Results: The objective response rate (ORR) in the whole population was 48% (6 CR, 65 PR, 51 SD ≥ 16 weeks), for an overall clinical benefit rate of 83%. At a median follow-up of 18 months (range 6-30), median PFS was 7.8 months (range 3-23+), median OS has not yet been reached. Major toxicities were expected and manageable with both the schedules, without differences in the ≥65 years pts (38%). Statistical analysis showed no predictive or prognostic value of the evaluated patient- and disease-related variables (DFI, tumor subtype, site and number of metastatic sites, previous taxane-based CT, prior lines for metastatic disease, dosing schedules), while the line of CT significantly affected both the probability of response (61% ORR in 2nd line versus 38% in ≥3 lines; p Conclusions: Our data confirm that both the tested nab-P regimens produce encouraging ORR and PFS values in taxane-pretreated MBC, in advanced lines of treatment too. The suggested higher activity of the q3w schedule in pts with more aggressive disease further supports the possibility of tailoring the dosing schedules according to the different patient profiles and clinical situations. Disclosure: All authors have declared no conflicts of interest.

e11573 Background: Several studies suggest that newer therapies can improve survival in MBC, but a different impact on overall survival (OS) is observed according to histology, extension of disease and prognostic factors. This survey was performed for evaluate Italian experience in cancer treatment in the last ten years. Methods: We collected data from 13 Italian Medical Oncology Unit; we registered all consecutive patients (pts) with breast cancer who have developed metastasis between 2000 and 2008. Demographic data, pathological characteristics and treatment were reported. OS was calculated from time of recurrence and stratified according to biological characteristics and to recurrence date. Results: 1542 pts was suitable for analysis; median age 61,7 (range 22-94); MBC at diagnosis 21,8%. Site of disease recurrence: bone 26,2%, visceral 25,4%, bone and visceral 20,7%, soft tissue 11,5%, soft tissue and visceral 8,4%, bone and soft tissue 7,8%. Molecolar classification: luminal A 66,3%, luminal B 14,5%, triple negative 11,5%, HER2+ like 7,7%. Pts received a median of 2 lines of chemotherapy (range 0-10) and 1 line of hormonal therapy (range 0-7); 22,5% received biological drugs. 15,5% of metastatic pts were enrolled in clinical trials. After a median follow up of 7.1 years 84,1% pts died (1297/1542 pts) and median OS was 2,7 years (range 2,6-2,9). We did not observe difference in OS for pts divided into 3 groups according to recurrence date (2000-2002, 2003-2005, 2006-2008). A longer median OS was observed in luminal B (3,8 years) versus luminal A and HER2+ like (2,8 years) and triple negative disease (1,2 years). Conclusions: Our survey describe a large number of MBC pts treated in 13 Italian Oncology Unit. OS analysis did not show significant differences according to recurrence date, but for different prognostic factors. OS data are superimposable to literature ones, showing a good transfer from clinical trials to clinical practice.

e11550 Background: Overall results from past and recent trials favor ovarian ablation, with luteinizing hormone-releasing hormone (LHRHa) analogues alone or in combination with the anti-estrogen tamoxifen (TAM), rather than with chemotherapy. The aim of this survey was to obtain more informations about the clinical practice of adjuvant endocrine therapy. Methods: 11 items electronic questionnaire was submitted to italian oncologists and 611 filled questionnaires were collected. The results were examined globally and according to sex, age, working institution and geographical origin of the oncologists. Results: 97.7% of patients less than 40 years needing only hormonal therapy would receive both TAM and LHRHa; 2.3% TAM or LHRHa alone. 93.6% of patients over 40 years would receive the combination with TAM or LHRHa When LHRHa would be added to TAM the treatment length would be: 5 years in 60% and 44%, 3 years in 20.8% and 26.4%, 2 years in 19.2% and 29.6%, in patients aged under and over 40 respectively. At least one risk factors like positive nodes, high ki-67, G3, vascular invasion, HER2 3+, influence neither the therapeutic options nor the length of LHRHa use. In patients under 40 with chemotherapy induced amenorrhea, the oncologists would prescribe: TAM in 22.4%, TAM and LHRHa in 68,1% (LHRHa for 5 years in 55.3%, for 3 years in 22.1%, for 2 years in 22.6%), aromatase inhibitor (AI) +/- LHRHa in 6.6%, LHRHa alone in 2.9%. A greater number of patients would be treated with AI among women aged over 40 (11%). The reasons to add LHRHa toTAM and the length of treatment would be: in higher efficacy of the combination: 45.5%; patient’s age: 30.1%; risk of recurrence: 20.8%; and, side effect: 3.6%. Conclusions: A high concordance between the Italian Oncologist attitude and the European Guidelines is confirmed by this large survey. However, a wide preference for a TAM/LHRHa combination is reported, as well as a significant preference for LHRHa and AI combination in women under 40 years with chemotherapy induced amenorrhoea.

e11502 Background: The combination of B with P as first-line treatment for patients (pts) with HER2-ve mBC showed clinical benefits in terms of progression-free survival (PFS) and objective respons...

e19093 Background: Patients with SCLC progressed after first-line chemotherapy (FL) have a poor prognosis and the evidence of a benefit of SL is still limited.This retrospective analysis evaluates the clinical outcomes of patients who received a SL treatment after failure of a FL for SCLC Methods: Retrospectively we reviewed 166 consecutive patients who failed a FL and received a second or third-line treatment, between 1993 and 2008 in 17 institutions. We divided patients for analysis in four subgroups, according to the type of SL administered: 1) Platinum-based (P) rechallenge 2) Non-platinum-based polichemotherapy 3) Non-topotecan monochemotherapy 4) topotecan monochemotherapy. Our endpoints were Overall survival (OS), Progression free survival (PFS) and Response Rate. Survival curves were designed with Kaplan-Meier method and Cox proportional hazard model was used for investigating factors which influence survival Results: Median age was 63 (range 25–86). Median OS from the SL was 6.2 months and PFS 2.9. 163 patients received a platinum based chemotherapy as FL, among them 67% obtained a response (CR=14%, PR=53.7%) and 19% had a progressive disease. 74% of patients had a PS 0–1 when started on SL. Moreover, 50 patients underwent also a third-line chemotherapy. Of the 23 CR at FL, 7 patients achieved a response in SL(30%), of the 85 PR only 19 (22%) and of the PD+SD only 6 (16%) (test for trend p=.03). No statistical differences among regimens groups were found; however, patients rechallenged with P went better then others when a long PFS in FL was demonstrated (p=.02) Conclusions: The clinical benefit of SL therapy for SCLC is poor and strictly dependent on response and on duration of response with FL treatment. Our retrospective analysis confirms that median OS for patients receiving SL is about 6 months and median PFS 2.9 months. A rechallenge with platinum should be the best options in patients with a long PFS in FL. Single agent topotecan, the most investigated agent in the literature, did not show evidence of superiority against other chemotherapy regimens No significant financial relationships to disclose.

11594 Background: Male breast cancer is an uncommon disease, 1%(0.7 %) of all breast cancer. Its aetiology, clinical behaviour and treatment are not well-known. The objective of our report was to analyze the form of presentation and the clinical evolution of patients with male breast cancer studied from 1987 to 2006. Methods: A total of 142 men with a diagnosis of breast carcinoma were registered and treated at the cancer-based hospitals linked to ORION collaborative group. 138 men had nonmetastatic breast carcinoma at diagnosis and were included in this analysis. Patients’ charts were retrospectively reviewed to obtain details of patient characteristics, adjuvant therapy, and outcomes. Analysis was performed with descriptive statistics; the log-rank test was used to compare outcomes. Results: The median patient age was 61.9 years (range, 38–84 yrs). Positivity for family cancer history: 16 out of 123 cases, 3 were unknown. Pathological characteristics included: pT1 tumors 22 pts (15.5%); pT2a 33 (23%), p...

2583 Background Among the several problems in planning and carrying out clinical trials with ex-vivo-generated, tumor antigen-loaded DCs for solid tumors, the pts selection, the optimal time to take blood for generating DCs and the impact on them of number and types of previous CT could also play a role. To date, high quantity of DCs can be generated after high-dose CT plus G-CSF in both BC and NHL pts. We investigated the DC yield obtainable from ABC pts in objective response after a SD, taxane-based CT program, considering these patients potentially candidate to DC-based vaccination programs. Patients and Methods Sixteen pts, aged 56 (range 43- 65), were studied 1 to 3 month after an objective response was obtained with a 1st-line CT (Epirubicin+Docetaxel combination at standard dosages, without the scheduled utilization of G-CSF) for their metastatic disease. DCs were generated from 25 ml of blood and following the standard procedure; the monocyte selection was performed with anti-CD14 microbeads (Milt...

Background. Dendritic cells (DC), the most specialized antigen-presenting cells, can be detected in the peripheral blood (PB) and divided into two subsets of populations, DC1 and DC2, endowed with different functions. The aim of this study was to evaluate the effect on DC release and on their subsets of three regimens utilized to mobilize CD34+ cells into the PB in cancer patients and in normal CD34+ cell donors. Patients and methods. The mobilizing sequences were: standard-dose epirubicin+taxol+granulocyte-colony-stimulating factor (G-CSF; 15 patients with advanced breast cancer), high-dose cyclophosphamide (CTX)+G-CSF (10 patients with breast cancer patients and 7 with non-Hodgkin's lymphoma, NHL), and G-CSF alone (5 normal donors of CD34+ cells for allogeneic transplantation). Comparative data were obtained from the steady-state PB of 20 healthy volunteers. For flow cytometric analysis, DC were gated as negative for specific lineage markers (CD3, CD11b, CD14, CD16, CD56, CD19, CD20, CD34) and positive for HLA-DR. The DC1 and DC2 subsets were defined as CD11c and CDw123 positive, respectively. Results. The percentages of DC at baseline and the time of CD34+ cell peak were: 0.48 and 0.51 for standard-dose chemotherapy (CT); 0.55 and 0.63 for breast cancer after high-dose CTX+G-CSF; 0.53 and 0.71 for NHL after high-dose CTX+G-CSF; and 0.51 and 0.54 for normal donors of CD34+ cells after G-CSF alone (all p=n.s.). Mean DC1/DC2 ratios in each study group at the time of CD34+ cell peak were 0.10, 0.12, and 0.18, respectively. Finally, in the group of healthy volunteers, the percentage of circulating DC was 0.95 and the mean DC1/DC2 ratio was 1.28. Conclusion. To our knowledge, this is the first report that demonstrates that both standard-dose or high-dose CT, when utilized together with G-CSF, do not induce DC mobilization into the PB, whereas a reversed DC1/DC2 ratio is observed. Furthermore, a lack of significant DC mobilization after G-CSF alone was also seen, in contrast to what was previously observed by others. These data should be taken in account when evaluating clinical correlations between DC number and CPC engraftment in both the transplantation setting, when monitoring the effects on the immune system of combinations of new drugs and/or cytokines, and when high numbers of DC are required for both experimental and clinical applications.

7040 Background: Chemotherapy is the only option for MPM. Cisplatin + pemetrexed became the standard in the first-line (FL), while the role of a second-line (SL) remains controversial. Methods: We ...

Purpose: Aim of this study was to investigate for the presence of existing prognostic factors in patients with bone metastases (BMs) from RCC since bone represents an unfavorable site of metastasis for renal cell carcinoma (mRCC). Materials and methods: Data of patients with BMs from RCC were retrospectively collected. Age, sex, ECOG-Performance Status (PS), MSKCC group, tumor histology, presence of concomitant metastases to other sites, time from nephrectomy to bone metastases (TTBM, classified into three groups: 5 years) and time from BMs to skeletal-related event (SRE) were included in the Cox analysis to investigate their prognostic relevance. Results: 470 patients were enrolled in this analysis. In 19 patients (4%),bone was the only metastatic site; 277 patients had concomitant metastases in other sites. Median time to BMs was 16 months (range 0 - 44y) with Median OS of 17 months. Number of metastatic sites (including bone, p = 0.01), concomitant metastases, high Fuhrman grade (p < 0.001) and non-clear cell histology (p = 0.013) were significantly associated with poor prognosis. Patients with TTBM >5 years had longer OS (22 months) compared to patients with TTBM