Search

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.

Although elderly patients are the first concerned by colorectal cancer (CRC), they are underrepresented in clinical trials. The real-world CASSIOPEE study was thus conducted in elderly patients treated for metastatic CRC (mCRC).This French prospective, multicenter, noninterventional study aimed to estimate 1-year progression-free survival (PFS) and overall survival (OS), and describe treatments, patient autonomy (Instrumental Activities of Daily Living; Balducci scale), and safety over 24 months, in patients older than 75 with mCRC, starting first-line bevacizumab plus chemotherapy (NCT01555762).From 2012 to 2014, 402 patients were included (safety population: n = 383, efficacy population: n = 358). Patient characteristics were as follows: mean age, 81 ± 4 years (80 years, 46%; 80-85 years, 44%;85 years, 10%); men, 52%; colon primary tumor, 80%; main metastatic site, liver 66%; Eastern Cooperative Oncology Group performance 0-1, 81%. Median PFS was 9.1 months (95% confidence interval [CI]: 8.3-10.2). It was superior for patients ≤85 years (80 years: 9.3 months; 80-85 years: 9.5 months) compared with patients85 years (8.3 months). Median OS was 19.0 months (95% CI, 16.5-21.5) and decreased in the 2 oldest groups (20.6, 17.8, and 13.0 months). Autonomy assessments decreased over time leading to nonconclusive results. Twenty-six percent of patients experienced serious adverse events (SAEs): 7% bevacizumab-related SAEs, and 6% bevacizumab-targeted SAEs. Two fatal bevacizumab-related adverse events were reported (hemorrhagic stroke and intestinal ischemia).This large French real-world study showed that medically fit older patients with mCRC could have a benefit/risk balance similar to that of younger patients when treated with first-line bevacizumab plus chemotherapy. Improvements in geriatric assessments are needed to better define this population.

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

Background Impact of comedications and comorbidities upon OS isn’t well described in cancer patients (pts). We aimed to evaluate their impacts on DFS and OS on pts resected from a stage III colon cancer and treated by adjuvant FOLFOX-4 +/- cetuximab in the PETACC8 study. Methods Treatments (trts) categories were defined according to the WHO ATC classification system. We focused on 4 medication classes: anticoagulant, cardiovascular, antidiarrheal and antidiabetic trts. We classified the 2559 pts in each category if they took trt at baseline or during study whatever the duration was. Kaplan-Meier method and Cox model were used to compare survival curves. Multivariate analyses were performed on the overall population and according to trt arm. Results Only 1% of pts had no comedications. Comedications with anticoagulant, cardiovascular, antidiarrheal and antidiabetic trts were observed respectively in 18%, 40%, 30% and 9% of the cases. Patients with antidiabetic or cardiovascular trts had more comorbidities. For each other comedication categories, baseline characteristics were balanced between pts treated or not. All comedication categories, except antidiarrheals, were associated with a significant decrease of DFS and OS (Table). Dose-intensity was balanced and may not explain survival differences. For pts treated with at least one cardiac, diabetic or anticoagulant trts, severe events were more frequently reported, including 9 early deaths. The use of antidiarrheals is maybe associated to a better exposure to chemotherapy as reflected by a higher rate of grade ≥3 adverse events but also a potential better efficacy. Table. Comedications impact on DFS and OS. Table . 549P Overall analysis DFS OS HR [95%CI] p HR [95%CI] p Anticoagulants Intake vs no 1.33 [1.10–1.62] .003 1.34 [1.07–1.67] .01 Antidiarrheals Intake vs no 0.87 [0.73–1.04] .12 0.78 [0.63–0.96] .02 Cardiovascular trts Intake vs no 1.20 [1.03–1.41] .02 1.28 [1.07–1.54] .01 Antidiabetics Intake vs no 1.37 [1.07–1.76] .01 1.45 [1.09–1.92] .01 Conclusions Comorbidities related to analyzed ATC classes negatively impact OS and DFS in PETACC8 pts, except antidiarrheal agents which positively impact OS and DFS. Clinical trial identification PETACC8; 2005-003463-23. Legal entity responsible for the study Federation Francophone de Cancerologie Digestive, Dijon. Funding Merck and Sanofi. Disclosure J. Taieb: Advisory / Consultancy: Merck; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Roche Genentech; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Amgen. All other authors have declared no conflicts of interest.

Background Standard adjuvant chemotherapy regimens for patients with node positive (N+) breast cancer consisted of anthracycline followed by taxane. The European Association for Research in Oncology embarked in 2000 on a phase III trial comparing 6 cycles of FEC 100 versus 4 FEC 100 followed by 4 Taxol. Primary end-point was disease free survival. Secondary end-points were overall survival, local recurrence free interval, metastases free interval and safety. Patients and methods Between March 2000 and December 2002, 837 patients were randomised between 6FEC 100 for 6 cycles (417 patients) or FEC 100 for 4 cycles then Taxol 175 mg/m 2 /3 weeks for 4 cycles (4FEC 100 -4T) (420 patients). One thousand patients had been planned initially but the trial was closed earlier due to slow accrual. Results Hazard ratios (HRs) were 0.99 for disease-free survival (DFS) (95%CI: 0.77–1.26; p = 0.91), and 0.85 for overall survival (OS) (95%CI: 0.62–1.15; p = 0.29). Nine-year DFS were 62.9% versus 62.5% for 6FEC 100 and 4FEC 100 -4T, respectively. Nine-year OS were 73.9% versus 77% for 6FEC 100 and 4FEC 100 -4T, respectively. Toxicity analyses based on 803 evaluable patients showed that overall grade 3–4 toxicities were similar in both arms (63% versus 58% for 6FEC 100 arm and 4FEC 100 -4T arm, respectively; p = 0.16). Conclusion In this trial replacing the last 2 FEC 100 cycles of 6FEC 100 regimen by 4 Taxol does not lead to a discernable DFS or OS advantage. The lack of a significant difference between the randomised treatment arms may however be due to a lack of power of this trial to detect small, yet clinically worthwhile, treatment benefits.

BACKGROUND: Tumour gene expression analysis is useful in predicting adjuvant chemotherapy benefit in breast cancer (BC). The 21-gene assay test is used to estimate the risk of recurrence and to predict the benefit of adjuvant chemotherapy (ACT) at an early stage of hormone-receptor-positive (ER+) BC. This study aims to examine the implications of RecurrenceScore (RS) testing within the routine clinical practices in France. METHODS: We conducted a prospective multicentert study, with voluntary participation, involving women with ER+, HER2-, BC. Performing the assay was left at the discretionof the physicians. The final treatment decision was discussed pre and post assay among tumor board (TB). The therapeutic changes after knowledge of RS were collected. RS and classical BC prognostic markers were investigated in parallel including an estimate of the budget impact of the assay. RESULTS: 603 patients were included in this analysis (tumor size ≤ 20 mm: 70.6%; node-negative patients: 61.2%; SBR 2: 74.9%). After the first TB, ACT was recommended for 529 patients (88.0%) and hormonotherapy (HT) alone for 74 patients (12.0%). The RS was low for 59.7% of the cases, intermediate for 34.0% and high for 6.3%. Based on RS results, second TB changed treatment decision for 70.48% of patients, avoiding CT in 64 % of cases. Only 24% received ACT while 76% received HT alone. The calculated budget impact as a minimal estimate according to the French healthcare payer perspective is estimated at a savings of € 570 per patient, corresponding to a global cost-saving of € 221,730. CONCLUSION: The results of this “real life” study confirm that the 21-gene assay had a significant impact on therapeutic decision. These findings warrant further consideration for the use of this genomic assay in patients with early stage BC in France. Citation Format: Gligorov J, Dohollou N, Mouysset JL, Laplaige P, Fignon A, Lafuma A, Michaud P. The 21-gene assay in the decision impact assessment of ER+, HER2- Breast cancer: A French real life prospective study [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 P6-07-28.

This prospective, observational study investigated the haematological response to darbepoetin alfa (DA) administered every three weeks for the treatment of anaemia. Response was also assessed according to baseline characteristics including iron, folate and vitamin B12 status.Anaemic adult patients with malignant non-myeloid cancer, starting or having already undergone chemotherapy received DA on day of inclusionand were followed up for up to 24 weeks. Concentration of haemoglobin (Hb), as well as iron, vitamin B12 and folate status where available, were recorded at inclusion, after a treatment period of 9 weeks and up to a maximum of 24 weeks or cessation of DA treatment, whichever was sooner.The main outcome measure assessed in this study was the percentage of patients reaching a Hb concentration of at least 11 g/dL at least once at any time during the study.A total of 2912 patients were included. The mean Hb concentration increased from 10.0 g/dL at inclusion to 11.4 g/dL at 9 weeks and 11.8 g/dL at 24 weeks. In 74.6% of patients the target Hb level of 11.0 g/dL or above was reached. After initiation of DA treatment, 9.5% of patients required a blood transfusion by week 9, and 5.6% thereafter. Vitamin B12 and folate status were unknown for 80.3% of patients and the iron status for 73.2% of patients. Compared with patients who remained untreated for vitamin B12 or folate deficiency, a higher percentage of patients with vitamin status within normal limits achieved the target Hb concentration. However, achievement of target Hb level appeared not to be affected by iron status.In this study, the mean Hb level increased in anaemic cancer patients treated with DA and the majority of patients achieved the target Hb level. In contrast to the recommendations of guidelines (EORTC) encouraging the measurement of iron and vitamin levels, the present study demonstrated that data were not routinely collected for these factors.

The aim of this Phase III, balanced randomised trial was to compare continuous intravenous infusion (CVI) of 5-FU with bolus (B) administration for metastatic colorectal cancer (CRC). One hundred and fifty-five non-pretreated patients were randomised to receive CVI 5-FU at a dose of 750 mg/m2/day (d), 7 d every 21 d (n = 77), or bolus 5-FU 500 mg/m2/d x 5 d every 28 d (n = 78). Incremental dose escalation at 50 mg per step was recommended in the absence of toxicity. All the patients had measurable metastatic disease (M), particularly, liver and a good performance status (WHO grade 0-1). Dose intensity was significantly higher in CVI than in the bolus group: 1369 mg/m2/week versus 558 mg/m2/week (P = 0.0001). Grade II-IV stomatitis was more frequent in the CVI group (31% versus 9%; P < 0.0001) as was hand and foot syndrome (14% versus 3%; P < 0.001). Diarrhoea (22% versus 12%) and grade III granulocytopenia (2% versus 6%) were comparable. Responses were more frequent in the CVI (26%) than in the bolus group (13%) (P < 0.04); progression-free survival was higher for the CVI group (P = 0.04), but there was no statistical difference in overall survival (median: 10 months (m) compared to 9 m), and 1 year survival (SD) 42% (6%) versus 40% (6%). In the multivariate analysis, survival was better for patients with a good PS, well-differentiated adenocarcinomas and a primary tumour without serosal extension. In conclusion, with a higher dose intensity, CVI 5-FU improved tumour control, but not overall survival.

3555Background: Approximately half of the patients (pts) with metastatic colorectal cancer (mCRC) are elderly. A real-life setting study was conducted in elderly pts (≥ 75 years-old) with mCRC trea...

3554Background: Few prospective studies specifically focused on the management of potentially resectable patients with mCRC. This prospective non-interventional cohort evaluated patients (pts) with...

This is the first double-blind clinical trial in a homogenous group of patients to compare the recommended dosing schedules of ondansetron and granisetron in the control of prolonged emesis after cycl

661 Background: In the randomized phase 3 VELOUR trial, aflibercept + FOLFIRI demonstrated a statistically significant overall survival benefit compared with FOLFIRI alone in metastatic colorectal cancer (mCRC) patients (pts) previously treated with an oxaliplatin-based regimen. Evidence from the VELOUR trial supported the initiation of a French clinical trial; AFEQT [NCT01670721] to capture utility values from QoL instruments and collect safety data from a target population similar to that in VELOUR. Interim data collected by French investigators are reported. Methods: AFEQT is single-arm, open-label trial evaluating safety and health-related QoL of aflibercept in mCRC pts previously treated with an oxaliplatin-based regimen. Estimated total enrollment is 200 mCRC pts. Eligible pts received aflibercept (4 mg/kg) q2wks on day 1 of each cycle followed by FOLFIRI up to disease progression, unacceptable toxicity, death, or investigator/patient decision, whichever occurred first. FOLFIRI starting dose and subsequent additional dose modifications were at the discretion of the treating physician. Safety assessments followed each cycle and continued until 30 days after last drug administration. The percentage of pts with grade 3/4 adverse events (G3/4 AEs) in the safety population of AFEQT was compared with that of VELOUR. Results: At data cut-off, the safety population comprised 123 pts with at least 1 completed cycle of treatment. Median age of pts was 64.6 vs. 61 years in VELOUR. At least 1 G3/4 AE was experienced by 67.5% of pts vs. 83.5% in VELOUR. Most reported G3/4 AEs were G3. There were no reports of G4 hypertension or diarrhea. Additional data will be reported during the meeting. Conclusions: In VELOUR, AEs occurred early in treatment, were often of single occurrence, generally reversible, and consistent with AEs commonly seen by oncologists. Interim safety analysis from AFEQT did not identify any new safety signal. Clinical trial information: NCT01670721. [Table: see text]

Background: Adding a taxane to anthracycline-based adjuvant chemotherapy prolongs survival in node-positive patients but optimal dose and schedule remain undetermined. This study aimed to select a dose-dense regimen for further assessment in phase III studies. Patients and methods: Ninety-nine patients with node-positive invasive breast adenocarcinoma were randomly assigned to docetaxel (Taxotere) (T) 75 mg/m2, epirubicin (E) 75 mg/m2 and cyclophosphamide (C) 500 mg/m2 (TEC) × 6, every 3 weeks; E 100 mg/m2, C 600 mg/m2 × 4, then T 100 mg/m2 × 4 (EC→T) or the reverse sequence (T→EC), every 2 weeks, with pegfilgrastim support. The primary end point was the incidence of grade 4 toxicity. Results: Dose intensity was almost doubled with dose-dense regimens, compared with TEC. Twenty-seven patients experienced grade 4 toxicity: 26%, 40% and 18% with TEC, EC→T and T→EC, respectively, mainly neutropenia, but febrile neutropenia occurred only in 11%, 10% and 3%. Grade 3–4 nail disorders, hand–foot syndrome and peripheral neuropathy occurred in 46%, 73% and 68% of patients with TEC, EC→T and T→EC, respectively. Conclusions: Dose-dense regimens yield more frequent and severe nonhematological toxic effects than standard dose TEC regimen. Though grade 4 toxicity rates appear acceptable with the T→EC regimen, the incidence of grade 3–4 events makes it difficult to recommend either dose-dense regimen for further investigation.

Aim: REG is a multi-kinase inhibitor with survival benefits in pts with pretreated mCRC, as demonstrated in the phase III CORRECT study. As a result, REG has been made available for medical practice use in the US, and in the EU. However, prescribing conditions in the real-life setting are known to be less stringent than selection criteria in clinical trials. The REgorafeniB in mEtastatic Colorectal cancer: a French Compassionate progrAm (REBECCA) is an ambispective cohort study designed to elucidate safety and effectiveness outcomes associated with REG as used in clinical practice for mCRC refractory to all available therapies. Methods: Pts were identified from the database of the French ATU (Temporary Authorization for Use), approved by the French Health Authorities to provide early access to innovative, not yet approved medicinal products such as REG. Baseline patient and tumor characteristics, REG dosing and dose-intensity, REG-related adverse events, pre- and post REG treatments, predictors of events, and effectiveness data (PFS, OS) were collected from pts who agreed, and whom physicians accepted to collaborate to the REBECCA study which had OS estimate as a primary objective. Results: 1178 pts met the ATU criteria, of whom 1119 started on REG. 681/1178 (58%) were male. Median age was 64 years (range 25-92). ECOG PS was 0 (31%), 1 (59%), and ≥ 2 (10%). Median time since diagnosis of the metastatic disease was 2.7 years. KRAS mutation was documented in 604/1178 (51%) of pts. Metastases were predominantly located in the liver (76%) and lungs (62%). The starting dose of REG was 160 mg/day in 89.7% of pts. Of the 1178 pts who met the ATU criteria, 787 pts treated by 283 physicians were included in the REBECCA study. Analyses in these patients are in progress. Conclusions: Apart from a baseline PS > 1 in 10% of the pts, the patterns of pts included in the ATU seem to be comparable to those of pts included in the phase III CORRECT study. REBECCA, which is the largest cohort study of REG in mCRC pts ever reported, will provide valuable insights in the therapeutic benefit of this new compound in the real-life setting. Full results of this study will be presented at the meeting. Disclosure: A. Adenis: Bayer (advisory board, research funding). All other authors have declared no conflicts of interest.

Aim: Though supportive care forms part of the overall management of cancer patients, little or no data compare how such care is perceived by patients and oncologists. Our objective was to understand patients' vs oncologists' perception of supportive care, fatigue, depression and other disorders associated with cancer and its treatments. Methods: A 43-item self-completion questionnaire was developed by a scientific panel of experts and sent by postal mail to 2,632 French oncologists. Simultaneously, a 29-item ‘mirror’ questionnaire was sent to patients undergoing cancer treatment Results: 414 oncologists (16%) and 118 patients completed the questionnaire from September to December 2013. While 47% of the patients think that adverse effects of treatments are unavoidable, and even demonstrate their efficacy (18% of respondents), 50% think that they can be reduced by supportive treatments. 84% of the oncologists give equal importance to supportive care and cancer treatment, and 58% state that they dedicate more time to supportive care than to the actual antitumor treatment. Oncologists reckon that cancer-related disorders are frequent in patients (fatigue: 73%, anxiety/depression: 39% and affective disorders and/or marital/relationship issues: 55%). However, not all symptoms are investigated by physicians on a regular basis. Patients' perception of cancer-related disorders is close to the physicians' estimation (fatigue: 86%, anxiety/depression: 37%, sleep disturbances: 81%). However, few patients spontaneously mention their symptom(s) to their physician. % of physicians investigating symptom on a regular basis (very often, during each consultation) % of patients who mention their symptom to their oncologist Fatigue 79% 87% Sleep disturbances 40% 37% Anxiety/depression 41% 51% Affective disorders and/or marital/relationship issues 7% 38% Conclusions: Though some symptoms (such as fatigue) are rather well managed with supportive care, other symptoms (such as sleep disturbances, depression, affective disorders or marital-relationship issues) should be further investigated by oncologists to enable their patients to speak out and ask for the management of such symptoms. Disclosure: J. Phelip: Pierre Fabre; L. Vanlemmens: Pierre Fabre; M.S. Dilhuydy: Pierre Fabre; P. Artru: Pierre Fabre Merck Amgen Sanofi; T. Bouillet: Pierre Fabre; C. Audigier-Valette: Pierre Fabre; F. Caroli-Bosc: Pierre Fabre; H. Cure: Pierre Fabre; G.M. Ganem: Pierre Fabre; L. Greillier: Pierre Fabre; P. Laplaige: Pierre Fabre; A. Marre: Pierre Fabre; P. Quittet: Pierre Fabre; P. Rouby: Pierre Fabre; F. Scotte: Pierre Fabre.

e14599 Background: Regorafenib (REG) is an oral multikinase inhibitor with survival benefits in patients (pts) with pretreated metastatic colorectal cancer (mCRC). The Temporary Authorization for U...

605 Background: In a randomized phase II study, P. Piedbois et al. explored a dose-dense docetaxel (T) followed by epirubicin/cyclophosphamide (EC) every two weeks versus the reverse sequence, versus standard-dose docetaxel, epiribucin and cyclophosphamide (TEC) every 3 weeks. The main purpose of this second analysis was to further explore the haematological safety of each regimen in patients receiving primary prophylactic pegfilgrastim. Methods: One hundred patients with node-positive invasive breast adenocarcinoma were randomized between (arm A) docetaxel 75 mg/m2, epiribucin 75 mg/m2 and cyclophosphamide 500 mg/m2 (TEC) every 3 weeks for 6 cycles (35 patients) or (arm B) epiribucin 100 mg/m2 and cyclophosphamide 600 mg/m2 every 2 weeks for 4 cycles, followed by T 100 mg/m2 (EC→T) every 2 weeks for 4 cycles (31 patients) or (arm C) T→ EC (34 patients). Among the 99 patients who received chemotherapy, 79 received pegfilgrastim 6 mg subcutaneous day 1 from the first cycle (27 in arm A, 23 in arm B and 29 in arm C). The safety data of these 79 patients were reported here. Results: Our results showed grade 3/4: neutropenia (arm A 30 %, arm B 39 %, arm C 31 %) and febrile neutropenia (FN) (arm A 11 %, arm B 13 %, arm C 3 %), grade 2–4: anaemia (arm A 26 %, arm B 61 %, arm C 55 %) and thrombocytopenia (arm A 15 %, arm B 9 %, arm C 3 %), respectively. Crude proportion and time to toxicity summaries showed that in dose-dense arms, patients allocated to the EC→ T sequence were more exposed to FN than patients allocated to the T→ EC. In the Cox model taking into account all allocated treatment and age, treatment was a predictor of grade 2–4 anaemia, whereas age was significantly correlated to grade 2–4 thrombocytopenia. There was no clear relationship between haematological toxicity and dose intensity across all treatment arms. Except for nausea (17 % versus 3 %) and neurological toxicity (13 % versus 3 %), non-haematological toxicities were similar in arm B and C. Conclusions: These analyzes confirmed that dose-dense regimens EC→ T or T→ EC are feasible with pegfilgrastim primary prophylaxis. The T→ EC sequence seems to be associated with a better haematological tolerance, and should be the preferred dose-dense regimen providing similar efficacy. The trial was supported by Amgen. No significant financial relationships to disclose.

647 Background: Administration of taxanes every 2 weeks (q2w), or “dose dense therapy”, is one of the most promising chemotherapy regimens in node positive (N+) breast cancer. AERO-B03 is a randomized phase II trial designed to assess the feasibility of docetaxel dose dense regimens in this setting. Methods: From December 2003 to September 2004, 100 patients (pts) with N+ breast cancer were randomized to receive 6 TEC (docetaxel 75 mg/m2, epirubicin 75 mg/m2 and cyclophosphamide 500 mg/m2 q3w) (control), 4 EC (epirubicin 100 mg/m2 and cyclophosphamide 600 mg/m2 q2w) followed by 4 T (docetaxel 100 mg/m2 q2w) (dose dense A) or 4 T followed by 4 EC (dose dense B). Pegfilgrastim was administered on day 2 of each cycle. Primary endpoint was grade 4 (G4) toxicity. Any of the 3 arms would be rejected from further study if G4 ≥ 50%. Data were reviewed by an independent safety monitoring committee. Results: Preliminary results are based on the first 61 pts (21 pts in control, 21 pts in dose dense A, and 19 in dose...