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Background In 2008, a study of the characteristics of hospitalised patients led to the development of a prognostic tool that distinguished three populations with significantly different 2-month survival rates. The goal of our study aimed at validating prospectively this prognostic tool in outpatients treated for cancer in terminal stage, based on four factors: performance status (ECOG) (PS), number of metastatic sites, serum albumin and lactate dehydrogenase. Patients and methods PRONOPALL is a multicentre study of current care. About 302 adult patients who met one or more of the following criteria: life expectancy under 6 months, performance status ≥ 2 and disease progression during the previous chemotherapy regimen were included across 16 institutions between October 2009 and October 2010. Afterwards, in order to validate the prognostic tool, the score was ciphered and correlated to patient survival. Results Totally 262 patients (87%) were evaluable (27 patients excluded and 13 unknown score). Median age was 66 years [37–88], and women accounted for 59%. ECOG PS 0–1 (46%), PS 2 (37%) and PS 3–4 (17%). The primary tumours were: breast (29%), colorectal (28%), lung (13%), pancreas (12%), ovary (11%) and other (8%). About 32% of patients presented one metastatic site, 35% had two and 31% had more than two. The median lactate dehydrogenase level was 398 IU/l [118–4314]; median serum albumin was 35 g/l [13–54]. According to the PRONOPALL prognostic tool, the 2-month survival rate was 92% and the median survival rate was 301 days [209–348] for the 130 patients in population C, 66% and 79 days [71–114] for the 111 patients in population B, and 24% and 35 days for [14–56] the 21 patients in population A. These three populations survival were statistically different (P Conclusion PRONOPALL study confirms the three prognostic profiles defined by the combination of four factors. This PRONOPALL score is a useful decision-making tool in daily practice.

Summary Background In 2013, the interim analysis of the Protocol for Herceptin as Adjuvant therapy with Reduced Exposure (PHARE) trial could not show that 6 months of adjuvant trastuzumab was non-inferior to 12 months. Here, we report the planned final analysis based on the prespecified number of occurring events. Methods PHARE is an open-label, phase 3, non-inferiority randomised trial of patients with HER2-positive early breast cancer comparing 6 months versus 12 months of trastuzumab treatment concomitant with or following standard neoadjuvant or adjuvant chemotherapy. The study was undertaken in 156 centres in France. Eligible patients were women aged 18 years or older with non-metastatic, operable, histologically confirmed adenocarcinoma of the breast and either positive axillary nodes or negative axillary nodes but a tumour of at least 10 mm. Participants must have received at least four cycles of a chemotherapy for this breast cancer and have started receiving adjuvant trastuzumab-treatment. Eligible patients were randomly assigned to either 6 months or 12 months of trastuzumab therapy duration between the third and sixth months of adjuvant trastuzumab. The randomisation was stratified by concomitant or sequential treatment with chemotherapy, oestrogen receptor status, and centre. The primary objective was non-inferiority in the intention-to-treat population in the 6-month group in terms of disease-free survival with a prespecified hazard margin of 1·15. This trial is registered with ClinicalTrials.gov, number NCT00381901. Findings 3384 patients were enrolled and randomly assigned to either 12 months (n=1691) or 6 months (n=1693) of adjuvant trastuzumab. One patient in the 12-month group and three patients in the 6-month group were excluded, so 1690 patients in each group were included in the intention-to-treat analysis. At a median follow-up of 7·5 years (IQR 5·3–8·8), 704 events relevant to disease-free survival were observed (345 [20·4%] in the 12-month group and 359 [21·2%] in the 6-month group). The adjusted hazard ratio for disease-free survival in the 12-month group versus the 6-month group was 1·08 (95% CI 0·93–1·25; p=0·39). The non-inferiority margin was included in the 95% CI. No differences in effects pertaining to trastuzumab duration were found in any of the subgroups. After the completion of trastuzumab treatment, rare adverse events occurred over time and the safety analysis remained similar to the previously published report. In particular, we found no change in the cardiac safety comparison, and only three additional cases in which the left ventricular ejection fraction decreased to less than 50% have been reported in the 12-month group. Interpretation The PHARE study did not show the non-inferiority of 6 months versus 12 months of adjuvant trastuzumab. Hence, adjuvant trastuzumab standard duration should remain 12 months. Funding The French National Cancer Institute.

IF 7.191 (2017); International audience; BACKGROUND:Previous studies showed that high and low body mass index (BMI) was associated with worse prognosis in early-stage colorectal cancer (CRC), and low BMI was associated with worse prognosis in metastatic CRC (mCRC). We aimed to assess efficacy outcomes according to BMI.PATIENTS AND METHODS:A pooled analysis of individual data from 2085 patients enrolled in eight FFCD first-line mCRC trials from 1991 to 2013 was performed. Comparisons were made according to the BMI cut-off: Obese (BMI ≥30), overweight patients (BMI ≥ 25), normal BMI patients (BMI: 18.5-24) and thin patients (BMI

En 2006, bevacizumab-FOLFIRI represente la therapie ciblee administrable des la premiere ligne chez les patients porteurs d’un cancer colorectal metastatique non operable. Une serie homogene de 111 patients colliges en region Bretagne et Pays de la Loire ayant recu du bevacizumab- FOLFIRI en premiere ligne en 2006 revele les resultats suivants: 51 reponses, 29 stabilites, 21 progressions et 10 toxicites avant evaluation. La mediane de survie globale (OS) est de 25,1 mois et la mediane de survie sans progression (PFS) de 10,2 mois. Dans le cas d’une chirurgie secondaire, l’OS median triple de 18,8 mois chez les patients non reseques versus 59,2 mois ceux reseques. En comparant les sujets âges de plus et de moins de 70 ans, aucune difference n’a ete mise en evidence en termes de benefice ou de risque. Bevacizumab-FOLFIRI pourrait etre administre en pratique courante chez les personnes âgees sous couvert d’une evaluation geriatrique et d’une approche multidisciplinaire.

Background: Chemotherapy (CT) is widely used in the management of estrogen receptor (ER) positive breast cancer patients (pts) pre-treated by hormone therapy (HT) . Single-agent CT in this setting has been validated in guidelines of management of the disease. Both paclitaxel and vinorelbine are recommended among the standard available CT agents for advanced breast cancer (ABC). Weekly paclitaxel (P) and oral vinorelbine (OV) as single agents are active with a good tolerance profile for these pts. Oral CT offers significant advantages over intravenous CT because of its greatest convenience, its ease of administration and reduced need for hospitalisation. Since the benefits and safety profile of OV and weekly P have never been compared in a face to face trial, this study will provide key clinical data regarding the optimal management of this patient population: ER positive and HER2-negative disease previously treated by a HT. Trial design: In this open-label study, pts are randomized to receive: OV 60 mg/m2/week (day 1, 8, 15) for the first cycle, then increased to 80 mg/m2/week from the second cycle in the absence of grade 3 or 4 toxicity or weekly P 80 mg/m2/week (day 1, 8, 15) intravenously. Treatments are continued until disease progression, unacceptable toxicity or pt's refusal. Main eligibility criteria include: age ≥18 years, documented locally recurrent or metastatic disease previously untreated by CT, ER positive disease previously treated by at least one HT, HER2-negative disease, Karnofsky PS ≥70. Primary objective: disease-control rate (defined as objective response or stable disease for a minimum of 6 weeks). Secondary objectives: other efficacy parameters, evaluation of safety profiles of both arms and quality of life assessment. Statistical methods: the one-sample multiple testing procedure for phase II clinical trials described by Fleming is used. This procedure employs the standard single stage test procedure at the last one of 2 pre-specified testings, while both allowing for early termination (should extreme results be seen) and essentially preserving the size and power of the single stage procedure. 124 pts will be enrolled in this randomized phase II study (62 per treatment arm). Randomisation is stratified according to prior taxane (yes or no) and presence of visceral metastases (yes or no). Disclosure: M. Aapro: Advisory Board Member, Pierre Fabre; M. Morand: Employee of Pierre Fabre Medicament; G.R. Villanova: Employee of Pierre Fabre Medicament. All other authors have declared no conflicts of interest.

Primary small-cell carcinoma (SCC) of the esophagus is rare, with about 200 cases reported up till now in the literature. Like pulmonary SCC, it is an aggressive tumor associated with a poor prognosis. Between 1994 and 1997, three patients with SCC of the esophagus were treated at Besancon University Hospital and this represented 1.85% of all esophageal malignancies diagnosed during this period: one patient had a limited tumor and underwent initial surgical resection, then chemotherapy with cisplatine and etoposide, and radiotherapy for recurrences. The other patients had extensive disease at diagnosis and were treated by the same chemotherapy. This retrospective study reports our experience of patients with this particular tumor and outlines the management strategy based on the available literature.

2086 Background: The OMIT (Drugs and Emerging Therapeutics Observatory) is a French structure created in 2003 by the Regional Health Agencies of Western France (Bretagne and Pays de la Loire). This...

595 Background: Metastatic colorectal cancer (mCRC) management has been clearly improved by targeted therapies such as anti VEGF and /or anti-HER1 drugs. The evaluation of the use of targeted therapies in the real world is strategic to assess health politics. OMIT Bretagne-Pays de la Loire is a network of private and public cancer centers that has been leading cohort studies evaluating Folfiri-bevacizumab treatment, the cost of targeted therapies and the succession of targeted therapies. Methods: The purpose of this study is to evaluate the benefit and safety of three consecutive targeted therapies in patients with KRAS wild-type unresectable mCRC. Sex, age, localization of the primary tumor site, successive chemotherapeutic regimens, toxicities, response rates, progression free survival and overall survival have been studied. Results: 34 patients (22 men, 12 women, median age 63 years [43-82]) have been prospectively recruited between 2003 and 2010. All of them received bevacizumab specially in association with FOLFIRI, cetuximab in association with irinotecan, panitumumab as monotherapy and others chemotherapies than FOLFOX, FOLFIRI, XELOX. The primary tumor site was colon (71%), junction (5%), and rectum (24%). 22 patients had metastatic colorectal tumor, 28 were operated on their primary tumor and 12 underwent resection after one line of treatment. Patients received successively 3 to 8 different lines of treatment for progressive mCRC. Toxicities of targeted therapies were manageable. Objective responses were observed in 38% (13) of the patients treated with BBR, 37% (11) treated with CBR and 25% (6) treated with P. Disease stabilization was achieved in 32% (11) of the patients treated with BBR, in 10% (3) with CBR and in 8% (2) with P. PFS at 80 months is 15%. Median OS from first metastatic line at death was 47.43 months (24.23-70.84). PFS and OS curves will be shown during the meeting. Conclusions: Our study clearly shows that patients receiving successively the three schedules (BBR, CBR, P) have a high overall survival with manageable side effects. No significant financial relationships to disclose.

Background: Since 2003, through the impetus given by Pr Erick Gamelin and the Regional Health Agency in Western France (Bretagne, Pays de Loire), a network called OMIT (Drugs and Emerging Therapeutics Observatory) has been created, including the Breast Cancer Forum. Anthracyclins and taxanes are the cornerstones of adjuvant chemotherapy for breast cancer. In France, since the PACS 01 publication1, FEC 100 followed by docetaxel 100 has been the standard adjuvant chemotherapy regimen in breast cancer. Long term toxicities like persistent alopecia or suboptimal hair regrowth have been observed.Methods: Over the last year, the first cases of persistent alopecia or suboptimal hair regrowth after adjuvant chemotherapy have been reported to the Breast Cancer Forum. Consequently, OMIT quickly drew up a case report form and mailed it to every oncologist in Western France to collect data.Results: From May 2008 to April 2009, 66 cases of persistent alopecia or suboptimal hair regrowth after adjuvant chemotherapy from 15 different institutions were declared to OMIT: median age: 60 years (35-78), hypothyroidia: 11, fine hair before treatment: 2. Alopecia was localized: 13, diffuse: 49, complete: 4. The time lapse between the end of chemotherapy and persisting alopecia has been more than 3 months: 5 patients, more than 6 months: 10, more than 12 months: 22, more than 24 months: 29. The chemotherapy regimens were various: schedule FEC (epirubicin 100 mg/msq), 3 courses followed by docetaxel 100 mg/msq, 3 courses: 54, docetaxel 100 mg/msq: 3, TCH (docetaxel-carboplatin-trastuzumab) or TH: 2, FEC 100: 2, epirubicin 75 mg/msq in association with docetaxel 75 mg/msq: 2. Hormonotherapy: letrozole: 13, anastrozole: 18, exemestane: 3, tamoxifene: 14, LH-RH agonist: 3. No hormonotherapy: 13. In some institutions, according to the ECOG trial2, some oncologists quickly decided to change their standard regimen from FEC 100 - docetaxel 100, to EC 100 4 courses followed by weekly paclitaxel for 12 weeks: forthcoming data on persistent alopecia, suboptimal hair regrowth or neuropathy after this ECOG adjuvant chemotherapy regimen will be presented at the symposium.Conclusion: For the first time in France, Western OMIT offers us data about persistent alopecia or suboptimal hair regrowth after adjuvant chemotherapy: it is an important side effect and must be considered by oncologists as optimal information to give to curable patients. The next step is to evaluate the real incidence of this phenomen on the population of patients treated by adjuvant chemotherapy for breast cancer: OMIT is currently working with the Federation Nationale des Centres de Lutte contre le Cancer (FNCLCC) to collect data from prospective trials such as PACS 01 (FEC versus FEC-docetaxel), PACS 04 (FEC versus epirubicin-docetaxel) and PACS 05 (FEC 6 courses versus 4 courses), to create the ALOPACS database.1- Roché H. Sequential Adjuvant Epirubicin-based Regimen and Docetaxel Chemotherapy for node-positive Breast Cancer Patients: the FNCLCC PACS 01 Trial. J Clin Oncol. 2006 dec 20; 24 (36) 5664-71.2- Sparano JA.Weekly Paclitaxel in the Adjuvant Treatment in Breast Cancer. N Engl J Med. 2008 Apr 17; 358(16): 1663-71. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3174.

Introduction L’efficacite du cetuximab seul ou associe avec la chimiotherapie dans le traitement du cancer colorectal metastatique (CCRM) est liee au statut mutationnel KRas. Les donnees CRYSTAL ont montre que l’association du cetuximab au FOLFIRI (FIRI) en 1 ere ligne de tt du CCRm ameliorait significativement le taux de reponse objective (RO) et la survie sans progression (SSP) (critere principal de jugement). Nous rapportons les donnees de survie globale (SG) et l’influence du statut KRas. Patients et Methodes L’ADN a ete extrait a partir d’echantillons tumoraux archives sur 578 des 1 198 patients randomises et le statut mutationnel KRas a ete determine sur les codons 12/13 par PCR quantitative specifique. Les bras de traitement ont ete compares par des tests de log rank bilateraux (5 % de significativite) pour la SSP et la SG, et par test de Cochran-Mantel-Haenszel (CMH) pour le taux de RO. Resultats Le groupe evaluable pour KRas (n = 540 ; 35,6 % de KRas mute) etait representatif du groupe en intention de traiter. Les patients ayant des tumeurs de type KRas non mute, avec l’ajout du cetuximab ont eu une augmentation significative de leur taux de RO (p = 0,0025), et de leur SSP (p = 0,0167). Leur mediane de SG a ete augmentee de 3,9 mois (cf tableau). Respectivement, 73,1 % et 68,6 % des pts (bras FIRI et bras FIRI + cetuximab) ont recu au moins une ligne de tt supplementaire et pour 25,4 % et 6,2 % d’entre eux un traitement par un anticorps anti-EGFR. Discussion Seule une partie des tumeurs ont pu etre retrospectivement analysee, mais nous rapportons l’importance du statut KRas non mute comme facteur de reponse et de SSP (p = 0,0167). Les SG sont importantes mais non significatifs probablement en raison d’un manque de puissance et des traitements de 2 eme ligne. Conclusion Les benefices de l’association du cetuximab a la chimiotherapie sont significatifs chez les patients de statut KRas non mute pour le controle tumoral. Le gene KRas est le premier biomarqueur utile de selection pour un traitement cible associe a une chimiotherapie standard dans le traitement de 1 ere ligne du CCR metastatique.

3641 Background: Once objective tumor response (OR) or stable disease (SD) has been achieved in patients (Pts) undergoing palliative chemotherapy (CT) for metastatic colorectal cancer (MCRC), we pr...

International audience; Background: In 2013, the interim analysis of the Protocol for Herceptin as Adjuvant therapy with Reduced Exposure (PHARE) trial could not show that 6 months of adjuvant trastuzumab was non-inferior to 12 months. Here, we report the planned final analysis based on the prespecified number of occurring events.Methods: PHARE is an open-label, phase 3, non-inferiority randomised trial of patients with HER2-positive early breast cancer comparing 6 months versus 12 months of trastuzumab treatment concomitant with or following standard neoadjuvant or adjuvant chemotherapy. The study was undertaken in 156 centres in France. Eligible patients were women aged 18 years or older with non-metastatic, operable, histologically confirmed adenocarcinoma of the breast and either positive axillary nodes or negative axillary nodes but a tumour of at least 10 mm. Participants must have received at least four cycles of a chemotherapy for this breast cancer and have started receiving adjuvant trastuzumab-treatment. Eligible patients were randomly assigned to either 6 months or 12 months of trastuzumab therapy duration between the third and sixth months of adjuvant trastuzumab. The randomisation was stratified by concomitant or sequential treatment with chemotherapy, oestrogen receptor status, and centre. The primary objective was non-inferiority in the intention-to-treat population in the 6-month group in terms of disease-free survival with a prespecified hazard margin of 1·15. This trial is registered with ClinicalTrials.gov, number NCT00381901.Findings: 3384 patients were enrolled and randomly assigned to either 12 months (n=1691) or 6 months (n=1693) of adjuvant trastuzumab. One patient in the 12-month group and three patients in the 6-month group were excluded, so 1690 patients in each group were included in the intention-to-treat analysis. At a median follow-up of 7·5 years (IQR 5·3-8·8), 704 events relevant to disease-free survival were observed (345 [20·4%] in the 12-month group and 359 [21·2%] in the 6-month group). The adjusted hazard ratio for disease-free survival in the 12-month group versus the 6-month group was 1·08 (95% CI 0·93-1·25; p=0·39). The non-inferiority margin was included in the 95% CI. No differences in effects pertaining to trastuzumab duration were found in any of the subgroups. After the completion of trastuzumab treatment, rare adverse events occurred over time and the safety analysis remained similar to the previously published report. In particular, we found no change in the cardiac safety comparison, and only three additional cases in which the left ventricular ejection fraction decreased to less than 50% have been reported in the 12-month group.Interpretation: The PHARE study did not show the non-inferiority of 6 months versus 12 months of adjuvant trastuzumab. Hence, adjuvant trastuzumab standard duration should remain 12 months.