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Background The phase III CLinical Evaluation Of Pertuzumab And TRAstuzumab (CLEOPATRA) trial established the combination of pertuzumab, trastuzumab and docetaxel as standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive locally recurrent/metastatic breast cancer (LR/mBC). The multicentre single-arm PERtUzumab global SafEty (PERUSE) study assessed the safety and efficacy of pertuzumab and trastuzumab combined with investigator-selected taxane in this setting. Patients and methods Eligible patients with inoperable HER2-positive LR/mBC and no prior systemic therapy for LR/mBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Prespecified subgroup analyses included subgroups according to taxane, hormone receptor (HR) status and prior trastuzumab. Exploratory univariable analyses identified potential prognostic factors; those that remained significant in multivariable analysis were used to analyse PFS and OS in subgroups with all, some or none of these factors. Results Of 1436 treated patients, 588 (41%) initially received paclitaxel and 918 (64%) had HR-positive disease. The most common grade ≥3 adverse events were neutropenia (10%, mainly with docetaxel) and diarrhoea (8%). At the final analysis (median follow-up: 5.7 years), median PFS was 20.7 [95% confidence interval (CI) 18.9-23.1] months overall and was similar irrespective of HR status or taxane. Median OS was 65.3 (95% CI 60.9-70.9) months overall. OS was similar regardless of taxane backbone but was more favourable in patients with HR-positive than HR-negative LR/mBC. In exploratory analyses, trastuzumab-pretreated patients with visceral disease had the shortest median PFS (13.1 months) and OS (46.3 months). Conclusions Mature results from PERUSE show a safety and efficacy profile consistent with results from CLEOPATRA and median OS exceeding 5 years. Results suggest that paclitaxel is a valid alternative to docetaxel as backbone chemotherapy. Exploratory analyses suggest risk factors that could guide future trial design.

Background: The aim of the study was to analyse the toxicity and health related quality of life (HRQoL) of breast cancer patients treated with FAC (5-fluorouracil, doxorubicin, cyclophosphamide) and TAC (docetaxel, doxorubicin, cyclophosphamide) with and without primary prophylactic G-CSF (PPG). Patients and methods: This was a phase III study to compare FAC and TAC as adjuvant treatment of high-risk node-negative breast cancer patients. After the entry of the first 237 patients, the protocol was amended to include PPG in the TAC arm due to the high incidence of febrile neutropenia. A total of 1047 evaluable patients from 49 centres in Spain, two in Poland and four in Germany were included in the trial. Side-effects and the scores of the EORTC QLQ-C30 and QLQ BR-23 questionnaires were compared in the three groups (FAC, TAC pre-amendment and TAC post-amendment). Results: The addition of PPG to TAC significantly reduced the incidence of neutropenic fever, grade 2–4 anaemia, asthenia, anorexia, nail disorders, stomatitis, myalgia and dysgeusia. Patient QoL decreased during chemotherapy, more with TAC than FAC, but returned to baseline values afterwards. The addition of PPG to TAC significantly reduced the percentage of patients with clinically relevant Global Health Status deterioration (10 or more points over baseline value) at the end of chemotherapy (64% versus 46%, P < 0.03). Conclusions: The addition of PPG significantly reduces the incidence of neutropenic fever associated with TAC chemotherapy as well as that of some TAC-induced haematological and extrahaematological side-effects. The HRQoL of patients treated with TAC is worse than that of those treated with FAC but improves with the addition of PPG, particularly in the final part of chemotherapy treatment.

Introduction The incidence of thrombosis associated with pancreatic cancer chemotherapy is high (22-36%), however the incidence in BDT is unknown. Table 1 . Clinical characteristics No VTE (n = 110) VTE (n = 26) Male 61 (55.5%) 15 (57.7%) Female 49 (44.5%) 11 (42.3%) Age, years Median (range) 64.5 (36.0-85.4) 64.3 (36.7-82.5) ECOG 0-1 75 (68.2%) 18 (69.2%) ECOG ≥ 2 21 (19.1%) 4 (15.4%) Unknown 14 (12.7%) 4 (15.4%) Central venous catheter No 93 (84.5%) 19 (73.1%) Yes 11 (10.0%) 4 (15.4%) Unknown 6 (5.5%) 3 (11.5%) Previous ATE: No 99 (90%) 24 (92.3%) Yes 11 (10%) 2 (7.7%) Previous VTE: No 107 (97.3%) 25 (96.2%) Yes 3 (2.7%) 1 (3.8%) Tumor site: Gallbladder 22 (20.0%) 4 (15.4%) Intrahepatic bile duct 40 (36.4%) 13 (50%) Perihilar bile duct 23 (20.9%) 6 (23.1%) Distal extrahepatic bile duct 17 (15.4%) 1 (3.8%) Unspecified/undetermined 8 (7.3%) 2 (7.7%) Stage Localized 28 (25.5%) 5 (19.2%) Locally advanced 32 (29.1%) 6 (23.1%) Mestastatic 47 (42.7%) 15 (57.7%) Unknown 3 (2.7%) 0 Khorana: 0-1 93 (84.5%) 21 (80.8%) 2 9 (8.2%) 2 (7.7%) ≥ 3 1 (0.9%) 0 Unknown 7 (6.4%) 3 (11.5%) Aim The aim of this study is to analyze the incidence of incidental and symptomatic VTE, and its chronological pattern, in patients with BDT receiving chemotherapy in ambulatory setting. Materials and Methods We conducted a retrospective study to determine the incidence of VTE in patients with BDT, treated at 6 hospitals of the Cancer & Thrombosis Working Group of the Spanish Society of Medical Oncology (SEOM). 136 consecutive patients diagnosed and treated with chemotherapy, were identified between January 2008 and December 2012 and included in this analysis. Results Clinical characteristics in Table 1. With a median follow up of 16.6 months (range 0.4-98.2), VTE was identified in 26 patients (19.1%): 10 pulmonary embolism, 9 deep vein thrombosis and 7 visceral vein thrombosis. All VTE occurred in patients with active tumor (2 locally advanced, 24 metastatic). 46% of the events were incidentally diagnosed. 62% of the events occurred in the first 6 months after diagnosis of cancer. Eight events were identified during the diagnostic workup of the neoplasm. Only 1 patient had a VTE recurrence (superficial venous thrombosis). A non-significant trend towards lower survival (OS) in patients with VTE (median OS 20.9 months vs 13.6 months; p = 0.066) was observed. Conclusions The incidence of VTE in patients undergoing chemotherapy for BDT in the ambulatory setting is high, but lower than that described in pancreatic cancer.

Background: Thirty percent to ninety percent of cancer patients suffer from pain, including neuropathic pain (NP), which results in great burden for cancer patients. Thus, it was of great interest to determine NP prevalence in cancer patients in Spain, to raise awareness of the condition, and aiming to improve management of cancer NP. Patients and methods: A 1-month follow-up prospective epidemiological multicenter study was conducted to assess prevalence and management of NP in Spanish oncologic units. The first 10 cancer patients at each unit diagnosed with NP by the validated Douleur Neuropathique 4 questionnaire (DN4) were recruited. Results: Of 8615 screened patients, 2567 (30%) suffered from pain. From these, 33% had NP according to investigators and 19% according to DN4 test. Three hundred and sixty-six patients (mean age 62.6 years; 61.2% male) were recruited. Pain decrease at 1 month was greater in patients with metastases (P < 0.01) and depended on treatment (P < 0.05), with 'oxycodone' showing 50.4% pain relief. Conclusions: NP prevalence in cancer pain is 33%. DN4 reports only about half the cancer NP cases diagnosed by clinicians. Pharmaceutical treatment of cancer pain, including NP, has a greater effect in patients with metastases and seems to depend on the specific treatment used.

Background Early and robust prediction of pathological response in neoadjuvant breast cancer may help to identify which patients may benefit from bevacizumab-based therapy. Different imaging and molecular approaches have been 0evaluated in a multicenter clinical trial. Methods 73 chemotherapy naive, stage II and III breast cancer (BC) patients (pts) were enrolled in a phase II, single-arm, multicenter, open-label and prospective clinical trial. Pts received single infusion of bevacizumab (15 mg/ kg) (C1) 3 weeks prior to the beginning of neoadjuvant chemotherapy (NAC) consisting of 4 cycles of docetaxel (60 mg/mq), doxorubicin (50 mg/mq) and bevacizumab (15 mg/ kg) every 21 days (C2-C5), followed by surgery. Tumor proliferation, hypoxia and perfusion were evaluated respectively using 18F-Fluorothymidine (FLT) and 18F-Misonidazole (FMISO) positron emission tomography (PET/CT) and dynamic contrast enhancement magnetic resonance (DCE-MR). Serial imaging studies were performed in parallel at several time points including baseline (BL) and 14-21 days after bevacizumab alone (C1). Biomarker expression was assessed by immunohistochemistry (Ki67, CD31, CD31/Ki67, VEGFR2, pVEGFR2 [Y951]) before and after bevacizumab infusion (C1). Gene expression was analyzed using Affimetrix Human Gene ST 1.0. Results Decrease in FMISO uptake >10% yielded a ROC curve area of 0.7 (95% CI: 0.56 - 0.85) with high specificity (94%). Decrease in the phosphorilation status of VEGFR2 (Y951) >70% yielded a receiver operating characteristic (ROC) curve area of 0.681 (95% CI: 0.536 - 0.825) with 84% sensitivity and 95% specificity. The change in phosphorilation status of VEGFR2p remains a significant predictor biomarker of response in multivariate analysis (OR = 0.9, IC%95 0.96-0.99, p = 0.04) after adjusting for clinical-pathological characteristics. Conclusion Our findings suggest that early changes on both biomarkers, FMISO and pVEGFR, with one cycle of bevacizumab alone predict pathological response in bevacizumab-based neoadjuvant therapy in breast cancer. Disclosure All authors have declared no conflicts of interest.

Aim: To describe patterns of use of adjuvant Interferon alfa-2b (IFN-a2b): dose, schedule, duration, adherence to therapy as well as others factors, in an unselected cohort of patients with high-risk melanoma, treated in different hospitals of Spain between January 2000 and December 2009. Methods: A multi-institutional retrospective clinical trial, including a statistically predefined sample of 325 melanoma patients with stage IIB, IIC or III and treated with adjuvant IFN-a2b was considered feasible to fulfill the study objective. Eligibility criteria include: 1) Pathologically confirmed diagnosis of cutaneous melanoma in the established period; 2) Complete resection of disease; 3) Adjuvant therapy with at least one dose of IFN-a2b; 4) Complete treatment details and follow-up data available; 5) Written informed consent in all patients that were alive at the time of review. Results: From June 2013 to January 2014, a total of 347 patients were included. As of April 2014, data analysis has been performed for 126 patients. Preliminary results in this cohort are presented: Median age: 59 years, male/female: 58%/42%. Pathological stage (AJCC 2009): IIB 15%, IIC 7%, IIIA 30%, IIIB 33% and IIIC 15%. Breslow thickness: 4mm 39%. Ulceration: 51.4%. 90% of patients received high-dose IFN-a2b and 10% either low or intermediate doses. High-dose IFN-a2b induction phase was completed by 88% of patients, and 70% completed the maintenance phase, although dose delay and dose reduction due to toxicity were common in both periods. Sixty percent of patients have relapsed as per investigator's review. Final analysis including disease-free and overall survival will be completed in July 2014. Conclusions: Most patients included in this preliminary analysis receive both, high dose IFN-a2b induction and maintenance phases, although dose delay and dose reduction are common. The complete analysis of this study will provide relevant and detailed information about the feasibility of IFN-a2b adjuvant treatment programs used for high-risk melanoma in Spain. These results will be relevant for the design and interpretation of future trials of adjuvant therapy. Disclosure: S. Martin-Algarra: In the past 36 months I have participated in Advisory Boards of MSD, BMS, Roche, GSK and Novartis. In the past 36 months have given lectures in events organized/sponsorized by BMS, Roche and GSK; G. Nocea: Employee of Merck Sharp and Dohme Spain; K. Stevinson: Employee of Merck US; P. Del Barrio: Employee of Merck Sharp and Dohme Spain; M.V. Tornamira: Employee of Merck Sharp and Dohme Spain; E. Espinosa: I am participated in the Advisory Board of MSD (Merck Sharp and Dohme). All other authors have declared no conflicts of interest.

Background: Limited information regarding incidence of chemotherapy induced nausea and vomiting (CINV) is available in patients receiving moderately emetogenic chemotherapy (MEC). Methods: Chemotherapy-naive patients receiving MEC, between April-2012 and May-2013 were included in an observational and prospective trial evaluating incidence of CINV during 120 hours post-chemotherapy as primary endpoint. Patients completed a diary to capture intensity of nausea and number of vomiting episodes. Complete response (no vomiting or rescue medication use) and complete protection (no vomiting and no severe nausea or use of rescue medication) were assessed as secondary endpoints. Results: Of 261 patients included, 240 were evaluated. The median age was 64.36 years (36.15-87.3), 44.17% were female and 11.25% were aged less than 50 years. The majority, 95.3% of patients received a combination of a 5-HT3 antagonist+corticosteroid as antiemetic treatment. Episodes of vomiting within 5 days of chemotherapy administration occurred in 20.78% of patients, nausea of any intensity in 42% (≥5 mm to 100mm VAS (visual analog scale)), and significant nausea in 23.8% of patients (≥25 mm to 100 mm VAS). An increase in the percentage of patients with severe nausea and vomiting was observed from the acute to the delayed phase, from 9.44% to 21.65% and from 9.24% to 15.45% respectively. Complete response in the acute phase was 85%, 77% in the late phase and 68.9% in the overall study period. Complete protection was 79.5% in the acute phase, 69.7% in the late phase and 62.4% throughout the study period. Physicians estimated prophylaxis would be effective (no vomiting or nausea and no use of rescue medication) for 75% of patients receiving MEC, compared with 54.1% obtained from patient's diary. Conclusions: Despite receiving prophylactic treatment, 31% of patients did not achieve a complete response and 38% patients did not achieve complete protection. In general nausea was worse controlled than vomiting. The results also showed the late phase was worse controlled than the acute phase in all variables. Healthcare providers overestimated the effectiveness of antiemetic prophylaxis. Disclosure: P. Del Barrio: Employee of Merck Sharp & Dohme; M.V. Tornamira: Employee of Merck Sharp & Dohme. All other authors have declared no conflicts of interest.

Background Aromatase Inhibitors (AI) are an important component in adjuvant therapy in postmenopausal women with positive estrogenic receptors in breast cancer. They inhibit the enzyme Cytochrome P450 CYP19, which causes a loss of BMD and consequently an increase in the risk of fracture. In patients with early breast cancer (EBC) in treatment with AI, it is estimated that the risk of fracture is 11% at five years. FRAX is used to calculate the probability of fracture at 10 years. Within its limitations, it should be highlighted that among its risk factors it does not include medications such as AI and that the treatment threshold adapted to patients of the Spanish population is not currently valid. Objectives To determine if the therapeutic intervention thresholds according to the FRAX proposed by the NOF (National Osteoporosis Foundation) as well as of the NOGG (National Osteoporosis Guidelines Group) identify appropriately whether patients with early breast cancer have a high risk of fracture at the start of AI treatment. Methods Retrospective and descriptive study of 73 patients with EBC in treatment with AI sent to the medical oncology department of a tertiary hospital (Basurto University Hospital) for monographic consultation of osteoporosis for its diagnosis, control and monitoring in the period from 01/01/2006 to 31/12/2010. A questionnaire was conducted of the risk factors, BMD DXA and FRAX. The FRAX results are described in the basal visit and the incidence of fractures in this population in December 2012 (monitoring period of 2 to 7 years). The patients with densitometric osteopenia and high risk of fracture according to the FRAX and the patients with both densitometric and established osteoporosis received treatment with bone agents by the Osteoporosis Unit. Results The mean age of our series is 63 years (40-83). The median time from the start of the AI and the realization of the basal BMD is 4 months. The initial densitometry identified 36 patients (49%) with osteoporosis, 35 patients (48%) osteopenia and 2 patients (3%) normal. According to the FRAX applying the treatment thresholds of the NOF (FMO >= 20% and FC >=3%): 19 patients (25%) have high risk of fracture: 16 patients (21%) of FMO and 18 patients (23.6%) of FC. Applying the treatment thresholds of the NOGG in which the values vary according to age: 3 patients (4%) have high risk of fracture, 1 patient (1%) of FMO and 3 patients (4%) of FC. Of the 73 patients, 15 (20%) present fracture, all vertebral, with 5 (33%) of high risk by FRAX according to NOF and only 1 (6%) according to NOGG. Conclusions In our series, the treatment thresholds for the FRAX of the NOF are more sensitive by identifying a greater number of patients with high risk of fracture (25%) than the NOGG (6%). Of the patients with fractures of the study (20%), only 33% of them were identified previously as high risk according to the NOF and 6% according to the NOGG. Both thresholds clearly underestimate the risk of fracture. It is necessary to validate the FRAX in prospective studies that include AI as a risk factor and apply new validated cut-off points in our population. Disclosure of Interest None Declared

e12016 Background: El Alamo project is a retrospective analysis of 26833 patients (pts) diagnosed of breast cancer (BC) between 1990 and 2001 across 43 of the main Spanish hospitals. Patterns of BC presentation, treatment and survival in the women population were analyzed. Methods: Three cohorts were analyzed: Alamo I (AI) with 4,532 pts diagnosed between 1990 and 1993; Alamo II (AII) with 10,791 pts diagnosed between 1994 and 1997; and Alamo III (AIII) with 11,277 pts diagnosed between 1998 and 2001. Data were collected by end of year 2000, 2003 and 2007 for AI, AII and AIII respectively. 468 items per pt were recorded, including demographic, therapeutic and outcome data. Results: Pts diagnosed with stage I were 17.6% in AI, 24.3% in AII and 32.7% in AIII; pts diagnosed with stage II were 55.5% in AI, 53.1% in AII and 44.9% in AIII; pts diagnosed with stage III were 18.7% in AI, 15% in AII and 15.7% in AIII; pts diagnosed with stage IV were 7.2% in AI, 5.9 in AII and 4.3% in AIII. Median age at diagnosis...

Abstract #2121 Introduction: Combinations can improve OS in MBC; however sequential single agent is sometimes preferred. In a recent report, pts receiving paclitaxel monotherapy in first line had a significantly worse OS if they were not receiving post study CT (PSC); no difference was seen in pts receiving paclitaxel+gemcitabine (Llombart, EBCC 2008). In this trial only 58% of pts received PSC. Purpose: To assess, outside the context of a clinical trial, the amount of MBC pts receiving CT beyond first line, as well as the impact of combination use and further CT lines in their OS. Methods: Alamo 1-2 is a breast cancer patient registry run by the GEICAM. 15482 pts diagnosed from 1990-1997 in 54 sites were included in the database. 4668 pts were stage IV; 778 (16.7%) metastatic at diagnosis and 3890 (83.3%) have had a recurrence. Results: 3045 (65%) pts received CT in first line, 83% were combinations (with anthracyclines 42%, CMF 16%, taxane+anthracyclines 9.4% or +other agents 8%) and 16% were monotherapy. Among other variables studied, only previous treatment (in early stage) was influencing the choice of a combination (pts without previous CT received more combinations than pts receiving CMF, than pts receiving anthracyclines). Median survival for pts receiving single agent was significantly shorter compared to pts receiving combination, 16.2 and 21.85 months (m) respectively, HR=1.37 (IC 95%: 1.21-1.55; p 65, negative hormonal receptor status, hepatic disease, Grade 3 and ≥ 3 disease sites. Half of the pts never received further CT after first line treatment. Only age and number of disease sites were influencing this decision in the Cox multivariate model. Median survival was 24.9 m in pts receiving further CT and 14.5 m in the ones not receiving it. In pts not receiving further CT, median OS was significantly shorter if they were treated with single agent in first line in comparison to those receiving previous combination: HR= 1.59 (IC 95%: 1.33-1.89; p< 0,00001). This difference was not significant in pts receiving further CT: HR= 1.15 (IC 95%: 0.97-1.37; p=0.101). Conclusion: Our data show that only half of the MBC pts receive further CT after first line; they have longer survival. We found significant evidence that further CT is impacting the OS in pts treated with single agent in first line, but not in those receiving previous combination. Those facts should be taken into consideration when selecting single agent or a combination in first line. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2121.

585 Background: El Alamo project is a retrospective analysis of 15381 patients (pts) diagnosed of breast cancer (BC) between 1990 and 1997 across 43 of the main Spanish hospitals. Patterns of BC pr...

6044 Background: El Alamo project is a retrospective analysis of 15381 patients (pts) diagnosed of breast cancer (BC) across 43 of the main Spanish hospitals. Methods: Two cohorts were analysed: Al...