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Background The BOLERO-2 trial reported efficacy and safety of Everolimus (EVE) and Exemestane (EXE) combination in HR+ advanced breast cancer (ABC) patients. The BALLET trial further evaluated the safety of EVE-EXE in HR+ ABC patients, without reporting efficacy data. Aim of the EVA real-life study was to collect data of efficacy and safety of EVE-EXE combination in the clinical setting, as well as exploring efficacy according to EVE Dose-Intensity (DI) and to previous treatment with Fulvestrant. Patients and methods This study aimed to describe the outcome of ABC pts treated with EVE-EXE combination in terms of median duration of EVE treatment and ORR in a real-life setting. Results From July 2013 to December 2015, the EVA study enrolled 404 pts. Median age was 61 years (33–83). Main metastatic sites were: bone (69.1%), soft tissue (34.7%) and viscera (33.2%). Median number of previous treatments was 2 (1–7). 43.3% of the pts had received Fulvestrant. Median exposure to EVE was 31.0 weeks (15.4–58.3) in the whole population. No difference was observed in terms of EVE exposure duration according to DI (p for trend = 0.27) or type of previous treatments (p = 0.33). ORR and Disease Control Rate (DCR) were observed in 31.6% and 60.7% of the patients, respectively, with the lowest ORRs confined in CHT pre-treated patients or in those who received the lowest DI of EVE. Grade 3-4 adverse events (AEs) were reported in 37.9% of the patients. Main AEs were: stomatitis (11.2%), non-infectious pneumonitis - NIP (3.8%), anaemia (3.8%) and fatigue (3.2%). Conclusions The EVA study provided new insights in the use of EVE-EVE combination in HR+ ABC pts many years after the publication of the pivotal trial. The combination is safe and the best response could be obtained in patients receiving the full dose of EVE and/or after hormone-therapy as Fulvestrant in ABC.

Background: Chemotherapy plus 1-year trastuzumab is the standard adjuvant treatment of HER2-positive breast cancer. The efficacy of less extended trastuzumab exposure is under investigation. The short-HER study was aimed to assess the non-inferiority of 9 weeks versus 1 year of adjuvant trastuzumab combined with chemotherapy. Patients and methods: HER2-positive breast cancer patients with node-positive or, if node negative, with at least one risk factor (pT>2 cm, G3, lympho-vascular invasion, Ki-67 > 20%, age 35 years, or hormone receptor negativity) were randomly assigned to receive sequential anthracycline-taxane combinations plus 1-year trastuzumab (arm A, long) or plus 9 weeks trastuzumab (arm B, short). This study was designed as a non-inferiority trial with disease-free survival (DFS) as primary end point. A DFS hazard ratio (HR)

Introduction: Breast carcinoma is the most common malignancy in women and the main cause of tumor deaths. Despite early recognition by screening and improvement in treatment regimens, many patients will eventually develop metastases, either locoregional recurrences or distant metastases, most frequently in the skeleton, liver and lung. Metastases to the gastrointestinal tract are infrequent and not even mentioned in the major oncologic textbooks. Case presentation: We report a case of metastasis to the stomach from occult breast cancer. The diagnosis was established by computed tomography (CT), histologic and immunohistochemical analyses of biopsies of the stomach lesion. The patient was treated with pre-operative hormonal therapy, undergoes breast surgery and then treated with systemic chemotherapy. She is still alive 2 years after initial symptoms of dyspepsia. Conclusion: The differentiation between primary gastric cancer and a metastatic breast tumor to the stomach is important for planning of treatment and to spare the patient unnecessary gastric surgery.

Background: This retrospective study evaluated the activity and toxicity profile of a regimen of vinorelbine and 5-fluorouracil with levofolinic acid, given to a large series of patients with recurrent or refractory metastatic breast cancer after first-line chemotherapy. Patients and Methods: Overall, 286 evaluable patients were included in the analysis. Two chemotherapy schedules were reviewed: a) the bolus regimen consisted of levofolinic acid 100 mg/m(2) and 5-fluorouracil 375 mg/m(2) both administered i.v. on days 1,2 and 3, plus vinorelbine 25 mg/m(2) i.v. bolus on days I and 8 every 3 weeks; b) the infusional regimen of levofolinic acid 100 mg/m(2) given as a 2-hour infusion, followed by 5-fluorouracil 400 mg/m(2) i. v. bolus and by 5-fluorouracil 600 mg/m(2) administered as 22-hour continuous venous infusion (c.v.i) for 2 days, plus vinorelbine i.v. bolus on days 7 and 8. Results: Overall, twelve patients achieved a complete response (4%; 95%CL 2%-7%) and 115 patients showed a partial response (40%, 95%CL 34%-46%), for an overall response rate of 44% (95CL 39%-50%). Sixty-one patients had stable disease (21%) and 98 patients progressive disease (34%). The tumor growth control rate was 63% (95%CL 60%-71%). Patients with soft tissue metastases as the dominant disease showed the highest response rate (56%), followed by viscera (48%) and bone (33%). The difference in response rate between patients with dominant visceral disease versus those with dominant bone disease was statistically significant (p=0.038). Patients treated with the bolus schedule achieved a 40% overall response rate with a 5% complete response rate, while those who received the infusional regimen had a 48% overall response rate with a 5% complete response rate. This difference was not statistically significant (P=0.164). The overall median duration of objective responses was 8.3 months (range 4-14 months), median time to progression of the all series was 61 months (range 2-24 months) and the median overall survival was 14.6 months (range 3-32). There was a statistically significant difference in survival among responder and non-responder patients (p=0.0009). Conclusion: The results of this large off-trial analysis confirmed the clinical activity and adverse-event profile reported in controlled clinical trials of the vinorelbine/5-fluorouracil with levofolinic acid regimen in clinical practice. This combination regimen was active with a low toxicity burden and, therefore, represents a good therapeutic choice for patients who require second-line chemotherapy.

BACKGROUND AND AIMS: oxaliplatin in combination with folinic acid (FA) and infusional 5-fluorouracil (5-FU) has shown significant anti-tumor activity in gastric cancer patients (FOLFOX). Previous studies have shown that gemcitabine (GEM), a new fluorinated anti-metabolite, enhances the individual anti-tumor activity of either 5-FU or oxaliplatin. We have therefore designed a multi-center phase II trial in order to test a novel GEM+FOLFOX-4 regimen in patients with metastatic gastric cancer. METHODS: we enrolled 36 patients, 28 males and 8 females, with an average age of 64.4 years (range 37-78), who received bi-weekly treatment with GEM (1,000 mg/m2 on day 1), levo-FA (100 mg/m2 on days 1 and 2), a 5-FU (400 mg/m2) bolus injection followed by 22-h continuous infusion (800 mg/m2) on days 1 and 2, and oxaliplatin 85 mg/m2 in a 4-6 h intravenous (i.v.) infusion before the second FUFA administration on day 2. RESULTS: the most frequent side effect was grade 1-2 hematological toxicity and late sensorial neurotoxicity. Two patients developed hypersensitivity to oxaliplatin while another developed an aseptic eosinophilic pneumonitis. Two patients refused to continue the treatment after two cycles of chemotherapy and were lost at the follow-up. Among the remaining 34 patients four achieved a complete response, 15 a partial response, 12 had a stable disease and three progressed. CONCLUSIONS: these results may grant the rationale to evaluate this multi-drug combination in randomized phase III trials in advanced gastric cancer.

Objective Eribulin mesylate (EM) is a fully synthetic macrocyclic ketone analogue of the marine natural product halichondrin. EM has been reported to be active in metastatic breast cancer. In this paper, we report efficacy and safety of data of EM in a retrospective, real-world series of patients with poor prognosis, hormone-refractory, or triple-negative metastatic breast cancer. Materials and methods The analysis was carried out at 4 interrelated oncology centers. EM was delivered at the dose of 1.4 mg/m2 in 100 mL of normal saline over 2 to 5 minutes on days 1 and 8 every 21 days. EM was continued until disease progression or unacceptable toxicity. Side effects were reported every cycle as per standard clinical practice and graded according to NCI-CTCAE, version 4.0. Time-to-progression and overall survival were reported. Results In this series of 90 patients the overall response rate was 22%, and 21% and 23% in the hormonal-resistant group and the triple-negative one, respectively. Stable disease was recorded in 24%, 21%, and 27%, respectively, in the whole series, the hormonal-resistant group, and the triple-negative one, respectively. Time-to-progression was 3.5 months (range, 1 to 22 mo) in the whole series and 3.0 months (range, 1 to 14.7 mo) and 3.4 months (range, 2.2 to 16.2 mo) in the hormonal-resistant group and the triple-negative one, respectively. Overall survival reached a median of 11.4 months. Conclusions This multicenter study, albeit retrospective, demonstrates the activity of this combination as third-line chemotherapy option in a challenging clinical setting such as triple-negative or hormone-resistant patients with breast cancer progressing after several lines of hormonal manipulations.

Background The aim of the study was to test the clinical efficacy and toxicity profile of gemcitabine (GEM) in combination with cisplatin (CDDP) in a series of patients affected by unresectable and/or metastatic biliary tree carcinoma (BTC) previously untreated with chemotherapy. Patients and methods Overall 38 consecutive patients who satisfied eligibility criteria (10 with gall-bladder carcinoma and 28 with bile duct carcinoma) were included in this phase II study. Median age was 61 years with median PS 1. Treatment included GEM 1000 mg/m2/week as 30 min i.v. on days 1 and 8, and CDDP 75–80 mg/m2 on day 1 with adequate hydration protocol and forced diuresis. Treatment was repeated every 3 weeks for three cycles before first re-evaluation of disease status. Results According to an intent-to-treat analysis a complete response (CR) was achieved in 1 patient (3%) with duration of 8 months. A partial response (PR) was recorded in 11 cases (29%; 95% CI 6% to 48%) with a median duration of 6.4 months (range 5–11 months) for an overall response rate (ORR) of 32%. Stable disease (SD) was seen in eight cases (21%), while the remaining 18 patients showed progressive disease (PD). Tumor growth control rate was 53%. Objective responses were recorded at loco-regional disease, liver and nodal metastases. Lung and peritoneal metastases did not respond. Time-to-progression was 4 months (range 2–11 months) and median overall survival was 8+ months (range 2–15 months). Side-effects were mild with few cases of grade 4 hematological toxicity. Transient and reversible liver toxicity was recorded in nearly one-quarter of patients. Infection without severe grade 4 neutropenia was observed in three cases. In no case was chemotherapy withdrawn for toxicity. Conclusions The GEM/CDDP regimen is active against advanced and/or metastatic BTC with a favourable toxicity profile. This regimen represents a reasonable therapeutic choice for palliation of advanced BTC. Inferences concerning overall survival are difficult to draw due to the phase II nature of the study.