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Resume Introduction La prise en charge de la douleur est un enjeu de sante publique important, particulierement en cancerologie. Dans une demarche d’evaluation des pratiques professionnelles, l’IRFC-FC a realise une enquete chez des patients presentant une tumeur solide metastatique osteophile en Franche-Comte. Les objectifs etaient d’evaluer la prevalence de la douleur, ses caracteristiques, sa prise en charge et son impact sur la qualite de vie. Methode Une enquete observationnelle, prospective et multicentrique a ete realisee via un questionnaire d’autoevaluation. Ont ete inclus les patients presentant un cancer metastatique du sein ou de la prostate pris en charge dans 5 hopitaux de jour de l’IRFC-FC sur une periode de 3 mois. Resultats Deux cent trente-trois questionnaires ont ete analyses. La prevalence de la douleur etait de 48,5 %. Trois-quarts des patients algiques avaient une douleur chronique de fond, d’intensite moderee a severe, associee ou non a des acces douloureux. Eu egard a l’intensite de leur douleur et a leur traitement antalgique, 42,0 % des patients semblaient sous-traites. Quatre-vingt-cinq pour cent des patients traites declaraient etre observants et estimaient que leur douleur etait bien prise en charge malgre un impact negatif sur la qualite de vie. Conclusion La mise en œuvre d’un chemin clinique est essentielle pour garantir une prise en charge standardisee, optimale et efficiente des patients algiques. L’evaluation de la satisfaction des soins et de la qualite de vie doit etre integree a la pratique clinique pour mieux identifier les patients algiques dont le traitement est inadapte.

Resume L’eribuline a obtenu son autorisation de mise sur le marche (AMM) en mars 2011 pour le traitement des patientes atteintes de cancer du sein localement avance ou metastatique ayant progresse apres anthracycline et taxane. L’objectif de cette etude etait d’evaluer retrospectivement l’efficacite, la tolerance et le cout de ce traitement chez les patientes traitees en Franche-Comte pour un cancer du sein metastatique (CSM) ayant recu l’eribuline. Quatre-vingt-dix patientes ont ete traitees par eribuline entre juillet 2006 et octobre 2013. L’âge median etait de 62 ans (35–83). La survie globale etait de 10,3 mois [IC 95 % : 7,6–17,9], la survie sans progression mediane de 3,8 mois [IC 95 % : 2,9–5,0]. Un benefice clinique a ete obtenu chez 55 % des patientes [IC 95 % : 43,1–66,9] evaluable selon les criteres RECIST. Les effets indesirables de grade 3 et 4 les plus frequents etaient la neutropenie (38 %), l’asthenie (10 %) et la neuropathie peripherique (7 %). Le cout median du traitement etait de 9767 € par patiente (6344–17 517). Cette analyse a retrouve des resultats comparables a l’etude EMBRACE malgre une population moins selectionnee. Une evaluation medico-economique de type cout–utilite permettrait d’evaluer l’efficacite de cette strategie therapeutique comparativement aux traitements standard.

The combination of cisplatin or carboplatin and etoposide is the standard treatment for certain poorly differen- tiated neuroendocrine cancers, such as small-cell lung cancer. The aim of this study was to assess the efficacy and tolera bility of the carboplatin-etoposide regimen in metastatic castra- tion-resistant prostate cancer (mCRPC). A total of 27 patients treated by carboplatin (area under the curve (AUC)=5) and etoposide (100 mg/m² intravenous infusion on days 1-3 or 75 mg orallyday for 10 days) for mCRPC were included for analysis. The median progression-free survival was 3.3 months (95% confidence interval (CI): 1.9-4.2) and the median overall survival (OS) was 8.1 months (95% CI: 4.06-12.36). The main grade 3-4 toxicities were haematological, namely anemia (33.3%), neutropenia (25.9%) and thrombocyto- penia (22.2%), whereas the most common non-hematological toxicity was asthenia (22.2%). The efficacy, compliance and safety profile were generally similar between the oral and intravenous etoposide groups. Pretreated patients with mCRPC may benefit from the carboplatin-etoposide regimen in terms of OS. The toxicities were acceptable, without reported treat- ment-related mortality. Therefore, the oral etoposide regimen may be an viable alternative for improving the quality of life of the patients. However, this regimen requires further prospec- tive investigation to confirm its efficacy.

BACKGROUND The addition of CAP to maintenance BEV demonstrated statistically significant and clinically relevant improvements in progression-free survival (PFS [primary endpoint]; HR 0.38 [95% CI 0.27–0.55]; log-rank p METHODS Pts with HER2-negative measurable mBC, ECOG PS RESULTS Adherence with questionnaire completion was 65–85% for all assessment timepoints during the first year of maintenance therapy. MMRM analysis of the global health status/QoL subscale showed no difference between the treatment arms in change from randomization (least squares mean estimate 0.40 [95% CI –6.07 to 6.87]). Similar results were observed for other subscales, including the diarrhea symptom subscale. No. of pts (%)BEV (N=94)BEV–CAP (N=91)Week 9aN=51N=59Improved15 (29.4)17 (28.8)Stable26 (51.0)34 (57.6)Week 18aN=29N=57Improved11 (37.9)12 (21.1)Stable12 (41.4)30 (52.6)Week 27aN=23N=43Improved7 (30.4)16 (37.2)Stable12 (52.2)20 (46.5)Week 36aN=15N=35Improved4 (26.7)14 (40.0)Stable9 (60.0)17 (48.6)aNo. of patients with completed questionnaires at both randomization and the respective week. Only weeks with ≥10 pts in both arms shown. CONCLUSIONS The IMELDA sample size was smaller than planned but protocol adherence with PRO completion was relatively high. Prespecified change from randomization and exploratory post hoc MMRM analyses of PROs suggest that the clinically meaningful PFS and OS benefit from adding CAP to BEV is achieved while maintaining QoL, with no difference between BEV and BEV–CAP treatments. Responder analyses over time showed improved or stable global health status/QoL scores in the majority of pts at each timepoint in both treatment arms. Citation Format: Dinesh Doval, Saverio Cinieri, Hakan Bozcuk, Jean-Yves Pierga, Kadri Altundag, Xiaojia Wang, Sudeep Gupta, Guillermo Lopez Vivanco, Vineet Gupta, Ewa Chmielowska, Jose Bines, Philippe Montcuquet, Alfred Namour, Emilio Alba, Giorgio Mustacchi, Paulo Cortes, Sabine de Ducla, Ulrich Freudensprung, Lesley Fallowfield, Joseph Gligorov. Exploratory post hoc analyses of patient-reported outcomes (PROs) in the IMELDA randomized phase III trial: Maintenance bevacizumab (BEV) ± capecitabine (CAP) after initial first-line BEV plus docetaxel (DOC) for HER2-negative metastatic breast can [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-12-16.

Background. The Oncotype DX recurrence score (RS) assay has been validated for prediction of 10-year risk of distant recurrence and likelihood of benefit from chemotherapy in patients with estrogen receptor (ER)-positive, HER2-negative early breast cancer. Patients with high RS tumors have substantial benefit, and patients with low RS tumors have minimal if any benefit from chemotherapy. Tumor size is used as a key parameter when selecting patients for neoadjuvant chemotherapy. The aim of this study was to assess the distribution of RS in patients selected for neoadjuvant chemotherapy primarily according to tumor size. Patients and Methods. Patients with ER-positive and HER2-negative tumors that were node-negative or had no more than 1 positive node from three trials were included in this study. Oncotype DX was performed at Genomic Health, Inc., blinded to the clinical data. Descriptive statistics were calculated for distribution of RS for all cases. Results. Of 277 patients, 96 met eligibility criteria, and 81 had sufficient material for analysis. Median tumor size was 40 mm (interquartile range [IQR], 30–50 mm). Grade I, II, and III were observed in 13, 49, and 17 cases, respectively. There was a wide distribution of RS with a median of 21.4 (IQR, 16.05-26.75). In total, 23 (28.3%) had high, 28 (34.6%) intermediate, and 30 (37%) low RS results. Conclusion. The RS may provide relevant information for neoadjuvant treatment decisions in select patients both in clinical practice and in studies. Inclusion of low RS disease patients in neoadjuvant trials will likely only dilute the ability to look at treatment effects.

The aim of this study was to determine the prevalence of adherence to adjuvant hormonal therapy (AHT) and to identify risk factors for medication non-adherence in clinical practice in patients with early-stage hormone receptor (HR)-positive breast cancer (BC) previously treated with chemotherapy. We carried out a cross-sectional, observational, prospective, and multicenter survey based on a structured self-report postal questionnaire (35 items investigating six areas). A sample of 474 patients was drawn from 676 patients potentially eligible. The structured and validated Morisky Medication Adherence Scale-4 items was used for measuring medication adherence. An analysis of risk factors for non-adherence to AHT was performed using a two-step approach: univariate, then multivariate analysis. A total of 280 patients out of the 428 analyzed patients participated in the survey, yielding a response rate of 65.4% [60.9–69.9]. The prevalence of adherence to AHT was estimated at 68.6% [63.1–74.0], corresponding to a high level of adherence. Three risk factors for non-adherence to AHT were identified: > 2 medications to treat comorbidities (p-value = 0.003), age less than 65 years (p-value = 0.008), and patient management in a university hospital setting (p-value = 0.014). Non-adherence is a common, complex, and multidimensional healthcare problem. This better understanding and knowledge of risk factors will allow healthcare providers (such as oncologists, general practitioners, pharmacists) to more easily identify patients at risk for non-adherence and help them provide appropriate information about AHT and its management, thus improving medication adherence in their patients.

Resume La signature genomique Oncotype DX ® est capable d’estimer le risque de recidive et de predire le benefice potentiel d’une chimiotherapie adjuvante pour un cancer du sein localise RE+ et HER-2 negatif. En 2012, grâce a l’Agence Regionale de Sante de Franche-Comte, ce test a ete disponible en routine dans la region. Les patientes pouvant en beneficier devaient presenter un cancer du sein localise RE+, HER-2-, avec un envahissement ganglionnaire absent ou limite a un ganglion sans rupture capsulaire et etre candidates a une chimiotherapie adjuvante sur les criteres histopathologiques et/ou cliniques classiques. En situation de limitations des ressources et de contraintes budgetaires, l’objectif de cette etude est d’evaluer l’impact economique de l’utilisation du test Oncotype DX ® en Franche-Comte. Pour y repondre, une evaluation de type minimisation de cout a ete realisee. Propose a 48 patientes, le test Oncotype DX ® a permis d’eviter une chimiotherapie adjuvante dans 73 % des cas. Cela se traduit par une absence de surcout lie a sa realisation, voire une economie potentielle pour l’Assurance-Maladie. Devant le succes de cette strategie pilote, la generalisation de l’utilisation du test Oncotype DX ® sur l’ensemble du territoire sous reserve d’une organisation stricte est a considerer rapidement par les autorites de sante.

Background. The primary aim of this retrospective study was to investigate intraindividual correlation of estrogen receptor (ER) status, progesterone receptor (PR) status, and HER2 status between primary breast cancer and metastatic breast cancer (mBC). Secondary aims included patients' characteristics, overall survival, feasibility of histopathological evaluation in the metastatic setting, and predictive factors associated with receptors status discordance. Methods. Patients with either biopsy of metastatic relapse or surgery of metastasis were identified. Demographics, tumor characteristics, treatment characteristics, and ER, PR, and HER2 statuses were retrospectively obtained in patients' reports. Receptors statuses were assessed by immunohistochemistry with a positivity cutoff of more than 10% for ER and PR. HER2 was considered as positive if overexpression was scored at 3+ in immunohistochemistry or if amplification ratio was >2 in fluorescent in situ hybridization. Results. From a cohort of 489 patients with mBC, 269 patients had histopathological samples of metastatic relapse. Histopathological analysis of the specimen confirmed the diagnosis of mBC in 235 patients. Discordance in one or more receptors between primary breast cancer and mBC was found in 99 patients (42%). A switch in receptor status was identified for ER in 17% of tumors (p = 4 × 10−3), PR in 29% of cancers (p < 4 × 10−4), and HER2 in 4% of lesions (p = .16). Exposure to chemotherapy and to anthracycline-based chemotherapy was statistically associated with switches in ER status. Seven (2%) second malignancies and three benign diseases (1%) were diagnosed. Conclusions. This study confirms that discordance in ER and PR receptor expression between the primary breast tumor and the corresponding metastatic lesions is high, whereas HER2 status remains relatively constant. Chemotherapy, and specifically anthracycline-based chemotherapy, was associated with switch in ER status. These results were obtained in a selected population of patients; further studies are warranted to confirm these data and to determine the interest of systematic rebiopsy in the metastatic setting.

Purpose: HER2 targeted therapies have substantially improved outcomes of patients with HER2 positive metastatic breast cancer (MBC). Medical records of patients with HER2 positive MBC achieving long survival were reviewed to describe their clinical characteristics and to assess whether curability is possible. Patients and methods: One thousand and seven hundred patients with MBC were treated between 01/01/2003 and 31/05/2012 in the 5 hospitals from the Franche-Comte region. All 217 patients with HER2 positive MBC region were retrospectively studied. Results: Among this population of HER2 positive MBC, 56 patients (26%) survived longer than 5 years. The characteristics of these long survivors were the following: median age at diagnosis was 55 years old (range, 33–87); 20 patients (35,7%) were metastatic at presentation; 20 patients (35,7%) had received adjuvant chemotherapy; the median disease-free interval was 17 months; brain, liver, lung, bone metastases were observed in 4 (7%), 19 (34%), 13 (23%), 23 (41%) in cases at occurrence of metastatic disease, respectively; tumours were hormonal receptors positive in 39 cases (70%) of these patients. A total of 16 (29%), 7 (12,5%), 7 (12,5%) and 26 (46%) cases had received 1, 2, 3 or more lines of chemotherapy at metastatic setting. The proportion of HER2 targeted treatment was 79%, 61%, 50% in first, second and third line, respectively. All patients received trastuzumab or lapatinib for their disease and 18 patients (32%) were given an anthracycline containing regimen. There were 7 complete response (CR), there were all observed after one line of chemotherapy based on trastuzumab combined with a taxane in all cases. Among these 7 patients, all continued trastuzumab after CR and all RH+ patients received hormonotherapy after CR. Among these 56 patients, 35 (62,5%) were still alive at the date cutoff in 31/05/2012. Conclusion: A significant proportion of patients with HER2 positive MBC were long survivors. Prospective clinical trials in this subset of patients should take into account this high number of patients with favorable outcome to achieve conclusion in term of survival. Can one consider the curabiblity of some MBC patients with HER2 overexpression? Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-18-22.

The aim of the study was to compare our reference adjuvant chemotherapy, FEC100 (fluorouracil 500 mg m(-2), epirubicin 100 mg m(-2) and cyclophosphamide 500 mg m(-2), six cycles every 21 days), to an epirubicin-vinorelbine (Epi-Vnr) combination for early, poor-prognosis breast cancer patients. Patients (482) were randomised to receive FEC100, or Epi-Vnr (epirubicin 50 mg m(-2) day 1 and vinorelbine 25 mg m(-2), days 1 and 8, six cycles every 21 days). The 7-year disease-free survival rates were 59.4 and 58.8%, respectively (P=0.47). The relative dose intensity of planned epirubicin doses was 89.1% with FEC100 and 88.9% with Epi-Vnr. There were significantly more grades 3-4 neutropenia (P=0.009) with Epi-Vnr, and significantly more nausea-vomiting (P0.0001), stomatitis (P=0.0007) and alopecia (P0.0001) with FEC100. No cases of congestive heart failure were reported, whereas four decreases in left ventricular ejection fraction occurred after FEC100 and five after Epi-Vnr. One case of acute myeloblastic leukaemia was registered in the FEC100 arm. After 7 years of follow-up, there was no difference between treatment arms. Epi-Vnr regimen provided a good efficacy in such poor-prognosis breast cancer patients, and could be an alternative to FEC100, taking into account respective safety profiles of both regimens.

Purpose To evaluate long-term cardiac function in patients without disease who had received six cycles of fluorouracil 500 mg/m2, epirubicin 50 mg/m2, and cyclophosphamide 500 mg/m2 (FEC 50) or the same regimen with epirubicin 100 mg/m2 (FEC 100) as adjuvant chemotherapy for node-positive breast cancer in the French Adjuvant Study Group–05 trial. Patients and Methods One hundred fifty patients (FEC 50, n = 65; FEC 100, n = 85) who were without disease and who gave their informed consent were enrolled for long-term cardiac assessment. The assessment included cardiac events occurring after the end of chemotherapy, vital signs, concomitant disease, ECG, isotopic left ventricular ejection fraction (LVEF), and echographic parameters. Abnormal files were blindly reviewed by cardiologists and oncologists. Results The median follow-up time was 102 months. After FEC 100, LVEF was less than 50% in five patients (radioisotopic method), and two patients experienced congestive heart failure (CHF) that was possibly related to treatment. Asymptomatic left ventricular dysfunction (LVD) was experienced in 18 patients after FEC 100 and in one patient after FEC 50. In these patients, treatment causality was probable in eight patients. Two additional years after this assessment, all 18 patients were still asymptomatic. Conclusion After more than 8 years of follow-up, the cardiac toxicity observed after adjuvant treatment with FEC 100 comprised two cases of well-controlled CHF and 18 cases of asymptomatic LVD. In the majority of women with primary breast cancer, the benefits of treatment with FEC 100 in terms of disease-free and overall survival outweigh the risks, and cardiac risk factors should be carefully evaluated in patient selection.

A total of 42 patients with cerebral metastases of malignant melanoma were included in this study of the nitrosourea fotemustine. The treatment plan consisted of a l-h i.v. infusion of 100 mg/m2 fotemustine every week for 3-4 weeks, followed by a 4- to 5-week rest period. Responding or stabilised patients then received 100 mg/m2 fotemustine every 3 weeks. Among the 39 evaluable patients, 2 complete responses and 9 partial responses were documented, leading to an overall response rate of 28.2%. Most of the responses were obtained in previously untreated patients and/or those presenting with a single cerebral metastasis. Toxicity was mild and mainly hematological, especially in patients previously treated by polychemotherapeutic regimen. Our study confirms the activity of fotemustine in cerebral metastases of disseminated malignant melanoma.

e11531 Background: There is a need to perform cost-effectiveness analysis for all new treatements approved for routine use based on national economical model. Eribuline, a new anti-microtubule inhibitor got approval for the treatment of patients with locally advanced or metastatic breast cancer who have progressed after an anthracycline, a taxane and a capecitabine containing regimens. Methods: All patients treated by eribulin in the Franche Comte region were prospectively monitored to assess efficacy, safety and cost-effectiveness of this new treatment based on a cost minimization strategy. The following costs were taken into account: drug, consultation with a medical oncologist, eventual supportive treatments, hospitalizations for treatment administration or for management of serious adverse events and the healthcare travels. Results: Ninety patients were treated by eribulin between July 2006 and October 2013. The median age was 58 (ranges: 32-79). A median number of 8 cycles (ranges 1 – 48) of eribulin...

e22085 Background: The Oncotype DX Recurrence Score (RS) assay has been validated for prediction of 10-year risk of distant recurrence and likelihood of benefit from chemotherapy in patients with E...

1122 Background: It is debatable whether sentinal lymph node (SLN), before chemotherapy in locally breast cancer (LBC) is feasible. Impact on survival and locoregionally recurrence are unknown. Methods: 256 consecutive patients with LBC treated in Franche Comté (France) between 2004 and 2010 by standard neoadjuvant chemotherapy were retrospectively studied. 177 patients underwent axillary lymph node (ALN) dissection after chemotherapy (cohort A) and 79 patients underwent SLN before chemotherapy (cohort B). The aim of this study was designed to confirm the feasible of SLN before neoadjuvant chemotherapy without negative impact of recurrence and survival. Disease-free survival (DFS) and overall survival (OS) were calculated using Kaplan-Meier method. Differences in OS and DFS according ALN exploration were tested for significance using the Log-Rank test. Results: No statistically significant differences were observed in terms of median age (respectively 59 and 48 years in cohort A and B), tumor size, histological type, grading score, estrogen receptor, progesteron receptor and human epidermal receptor-2 status. No difference of breast conserving surgery was observed between cohort A and B (56.25 vs. 64.56%, p = 0.21). In cohort B, 38 patients (48.10%) of patients underwent SLN alone. For others patients (n = 41, 51.90%), secondary complete axillary lymphadenectomy was performed in the same time of breast surgery. After a median follow up of 57 months (range: 38-105), there was no significant difference in termsof local and axillary recurrences (1.13 vs. 1.27%), metastatic recurrence (11.30 vs. 11.40%). Five-year DFS (76 vs 81%, p = 0.55) and 5-year OS (91 vs. 97%, p = 0.76) did not differ between patients in cohort A and B. Conclusions: SLN before neoadjuvant chemotherapy is feasible and allows to avoid ALN dissection in nearly 50% of patients without impact on recurrence and survival.

e11579 Background: Clusterin (CLU) is a glycoprotein expressed constitutively in many tissues and involved in various physiopathological processes. Despite CLU expression is dysregulated in many types of cancer, the specific role of CLU in tumorigenesis remains unclear. The identification of several forms of the protein, with multiple roles is an explanation for these conflicting results. Cytoplasmic CLU (cCLU) has a role in breast tumorigenesis, cancer progression and is associated with breast cancer cell lines death in vitro. However contradictory data are reported about prognostic value of cCLU on survival and clinical progression. Our objective was to estimate patient’s overall survival (OS) according to the expression of cCLU. Methods: Histological and clinical data of 158 patients diagnosed with breast cancer were retrospectively recorded. Every patients were treated in a single French university hospital between 1993 and 2001. Histological samples had been reviewed to determine hormonal status, HER2 and clusterin expression. Immunohistochemical techniques were based on standards and recommendations applied at the time of analysis. Tumors were defined as cCLU positive (cCLU +) if its expression was superior to 10%. Overall Survival rates along with standard deviations were estimated using the Kaplan-Meier method. Differences in OS according to cCLU expression were tested for significance using the log-rank test. Results: Patients had a median age of 56 years (31 – 82 years). Among the 158 patients analyzed, cCLU was overexpressed in 31 patients (19.62%). The histopathologic and clinical characteristics were not statistically different according to clusterin expression even if a trend favouring less favourable tumoural characteristics were observed in cCLU positive tumour. The median follow-up was 14.1 years (11.3 - 19.3). In univariate analysis, cCLU overexpession were not related to OS (HR = 0.86; CI95%: 0.43 - 1.70). Ten-year OS was 76% (± 4) among patients with cCLU - tumors vs 77% (± 7) in patients with cCLU + tumor (p = 0.66). Conclusions: cCLU expression does not seem to be a pronostic factor of overall survival.

A total of 70 patients presenting with a disseminated malignant melanoma were entered into a multicentric study of combination chemotherapy using dacarbazine and fotemustine. In all, 63 patients were evaluable, 31.8% of whom had previously received cytotoxic chemotherapy. The protocol consisted of induction treatment with a weekly infusion of 100 mg/m2 fotemustine on days 1 and 8 and a daily infusion of 250 mg/m2 dacarbazine on days 15/18 followed by a 4- to 5-week rest period. Responding and stabilized patients were given maintenance treatment comprising fotemustine (100 mg/m2, day 1) and dacarbazine (250 mg/m2, days 2/5) every 3 weeks. The response rate was 33.3% (9 complete responses (CRs) and 12 partial responses (PRs)) and was outstanding among pretreated patients (34.9%). Responses were also documented in cerebral (28.6%), visceral (23.1%) and nonvisceral (43.3%) metastatic sites. Toxicity was mainly hematologic (22.2%, grade III/IV leukopenia; 20.3%, grade III/IV thrombocytopenia) and was acceptable. These results are encouraging in terms of the antitumor activity against nonvisceral metastases (43.3%) and the percentage of CRs obtained (23.3%), and they confirm the activity of fotemustine in cerebral metastatic sites.

660 We analyzed retrospectively the influence of delay between surgery and adjuvant chemotherapy on disease-free survival (DFS) in operable, breast cancer patients. Methods - Among eight FASG trial...