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PURPOSE Palbociclib is a cyclin-dependent kinase 4 and 6 inhibitor approved for advanced breast cancer. In the adjuvant setting, the potential value of adding palbociclib to endocrine therapy for hormone receptor–positive breast cancer has not been confirmed. PATIENTS AND METHODS In the prospective, randomized, phase III PALLAS trial, patients with hormone receptor–positive, human epidermal growth factor receptor 2–negative early breast cancer were randomly assigned to receive 2 years of palbociclib (125 mg orally once daily, days 1-21 of a 28-day cycle) with adjuvant endocrine therapy or adjuvant endocrine therapy alone (for at least 5 years). The primary end point of the study was invasive disease-free survival (iDFS); secondary end points were invasive breast cancer–free survival, distant recurrence-free survival, locoregional cancer-free survival, and overall survival. RESULTS Among 5,796 patients enrolled at 406 centers in 21 countries worldwide over 3 years, 5,761 were included in the intention-to-treat population. At the final protocol-defined analysis, at a median follow-up of 31 months, iDFS events occurred in 253 of 2,884 (8.8%) patients who received palbociclib plus endocrine therapy and in 263 of 2,877 (9.1%) patients who received endocrine therapy alone, with similar results between the two treatment groups (iDFS at 4 years: 84.2% v 84.5%; hazard ratio, 0.96; CI, 0.81 to 1.14; P = .65). No significant differences were observed for secondary time-to-event end points, and subgroup analyses did not show any differences by subgroup. There were no new safety signals for palbociclib in this trial. CONCLUSION At this final analysis of the PALLAS trial, the addition of adjuvant palbociclib to standard endocrine therapy did not improve outcomes over endocrine therapy alone in patients with early hormone receptor–positive breast cancer.

507 Background: State-of-the-art adjuvant endocrine therapy with aromatase inhibitors (AI) compromises bone health in postmenopausal patients with hormone receptor-positive (HR+) breast cancer, increasing fracture incidence. Adjuvant treatment with the anti-RANK ligand denosumab (Dmab) counteracts these side effects and may improve outcomes. We here report the final long-term outcomes of the ABCSG-18 trial (ClinicalTrials.gov NCT00556374). Methods: In this prospective, double-blind, placebo-controlled, phase 3 trial, 3,425 postmenopausal patients with early HR+ breast cancer on AI therapy were randomised in 58 trial centers between 2006 and 2013 to receive either Dmab 60 mg or placebo s.c. every 6 months (q6m). The primary endpoint was time to first clinical fracture, secondary disease outcome-related endpoints were disease-free survival (DFS), bone-metastasis free survival (BMFS), and overall survival (OS). In addition to the main endpoint analyses reported previously, exploratory long-term follow-up was conducted in ABCSG-18. Main time-to-event analyses were based on stratified Cox models. Sensitivity analyses accounting for treatment cross-over associated with a late Dmab open-label phase, as well as for receiving any anti-resorptive agents were performed. Results: For this final protocol-defined analysis, median follow-up is 8 years (Q1,3: 6, 9.6), and all patients had ended their randomly assigned double-blind treatment (Dmab 60mg s.c. q6m n = 1711; placebo s.c. q6m n = 1709) for a median of 5 years. DFS was improved in the Dmab group versus the placebo group (309 versus 368 DFS events, hazard ratio (HR) 0.83, 95% CI 0.71-0.97, p = 0.016), resulting in an absolute 9-year DFS difference of 3.5% (79.4% vs 75.9%, respectively). When censoring for late cross-over and use of anti-resorptive agents, the DFS difference was confirmed (HR 0.82, p = 0.010). BMFS was improved by 19 per cent (HR 0.81, 95% CI 0.65-1.00, p = 0.047) in the Dmab group, and OS was improved by 20 per cent in the uncensored analysis (127 versus 158 OS events, HR 0.80, 95% CI 0.64-1.01, p = 0.065), and 26 per cent after censoring (HR 0.74, 95% CI 0.58-0.94, p = 0.013). The previously reported marked reduction in clinical fractures persisted even long-term, with 201 fractures in the Dmab and 255 fractures in the placebo group (HR 0.76, 95% CI 0.63-0.92, p = 0.004). No new toxicities for this (low) bone-protective dose of adjuvant Dmab were reported, particularly no ONJ occured.. Conclusions: Adjuvant Dmab 60mg every 6 months during AI therapy is safe, and markedly reduces treatment-induced clinical fractures even in the long-term. DFS, BMFS, and OS are improved in this descriptive final long-term analysis of ABCSG-18. Adjuvant denosumab should be considered for routine clinical use in postmenopausal patients with HR+ breast cancer. Clinical trial information: NCT00556374.

12083 Background: Evidence-based antiemetic guidelines offer predominantly consistent recommendations for CINV prophylaxis. However, studies and surveys suggest that adherence to these recommendations is suboptimal. We explored potential inconsistencies between clinical practice and guideline-recommended treatment with a registry evaluating the effect of guideline-consistent CINV prophylaxis (GCCP) on patient outcomes. Methods: This was a prospective, non-interventional, observational, multicenter study designed to assess overall (0-120 h) complete response (CR: no emesis/no rescue use) rates in patients who received GCCP or guideline inconsistent CINV prophylaxis (GICP) using diaries for 5 days following chemotherapy. Cycle 1 results are presented in patients who received either 1) anthracycline/cyclosphosphamide (AC) highly emetogenic chemotherapy (HEC), non-AC HEC or carboplatin, with GCCP for all these groups consisting of prophylaxis with an NK1 receptor antagonist (RA), 5-HT3RA, and dexamethasone (DEX) prior to chemotherapy or 2) moderately emetogenic chemotherapy (MEC), with GCCP consisting of a 5-HT3RA and DEX prior to chemotherapy as per MASCC 2016 guidelines. CR rates for cohorts deemed to be GCCP and GICP were compared using a chi-square test. Results: A total of 1,089 patients were part of the cycle 1 efficacy evaluation. Overall GCCP was 23% for all patients. CR rates were significantly higher in patients receiving GCCP versus GICP (Table). Conclusions: Consistent with prior studies, GCCP was very low. The primary endpoint of the study was achieved as there was a significant benefit of almost 10% improved prevention of CINV when administering GCCP. As per MASCC/ESMO guidelines such an absolute difference should be practice changing. Comprehensive multifaceted strategies are needed to achieve better adherence to antiemetic guidelines. [Table: see text]

e12114 Background: Her2-positive (Her2pos) breast cancer (BCa) is the second most lethal subtype of BCa. The treatment of Her2-positive BCa was revolutionized due to the dual use of trastuzumab and pertuzumab (T+P) in recent years both in the neoadjuvant and the palliative setting. Although several years have passed after initial approval of these drugs, single-center outcome data as reported by clinicians is sparse. In this retrospective study, we set to assess outcomes measures at our institution, Austria’s largest academic hospital, for the use of T+P in early and metastasized BCa. Methods: We acquired records on combined pertuzumab and trastuzumab orders from our intramural drug order software (CATO, Cato Research, Durham, NC, USA) for the time period of May 2013 to March 2018. Further, using electronic patient histories, we described both the neoadjuvant and palliative patient groups by assessment of body weight/size, tumor stage, histology including immunohistochemistry (IHC), lines of oncological therapies received, ejection fraction (EF) drops>10%, deaths and most importantly the outcomes measures pathological complete response (pCR, neoadjuvant cohort) rate and progression-free survival (PFS, palliative cohort). Results: 120 breast cancer patients were given dual therapy with T+P. The neoadjuvant cohort contained 63 patients, while the palliative cohort included 57 patients. All patients included were female. Full histology including IHC data was available for 47 of 63 patients in the neoadjuvant cohort and 30 of 57 patients in the palliative cohort. BMI was 25.6 and 23.3, respectively, on average. The mean age was 54 years in the neoadjuvant and 56 years in the palliative cohort. 73.6% (39/53) and 65.9% (29/44) of tumors were ER positive as determined by IHC. While neoadjuvant patients obtained an average of 6.5 cycles, patients within the palliative cohort received a mean of 17.3 cycles of T+P. 0 and 17 deaths were observed in the respective cohorts. Data on pCR and PFS was available for 95.2% and 91.2% of patients, respectively. The pCR rate within the neoadjuvant cohort was 46.7% (28/60), and mean PFS across all treatment lines of the palliative cohort was 10.2 months. Conclusions: We report retrospective single-center outcome data for the combined use of trastuzumab and pertuzumab in both early and metastatic Her2pos BCa in line with previously published data.

e12527 Background: RIB + aromatase inhibitor (AI) is approved as 1L treatment (tx) for HR+, HER2− MBC. Real-world data on efficacy and safety of RIB+AI are limited. REACHAUT, a prospective, noninterventional trial assessed the safety of RIB+AI in 1L setting in postmenopausal patients (pts) with HR+, HER2− MBC in a real-world setting. First interim analysis results about safety are presented. Methods: 75 postmenopausal pts with HR+, HER2− MBC, QTc < 450 msec, and no prior ET for advanced disease were enrolled at 13 sites. 1L chemotherapy (CT) was allowed. Results: At data cutoff (25-Jan-2019), 61 pts were evaluable for safety (ongoing, n = 44; discontinued, n = 17). Median duration of follow-up was 29 d. Median age at baseline was 65 y ( < 65 y, n = 28; ≥65 y, n = 33); ECOG performance status was 0 (n = 39) and 1 (n = 12). 42.6% had visceral (lung, liver) metastases (mets), while 34.4% had bone only mets. Most common prior tx included CT (29.5% in neoadjuvant/adjuvant/metastatic setting) and ET (41%). Pts received RIB in 1L (93.4%) and second-line (6.6%) setting. In 80.3% pts receiving RIB, the ET partner included letrozole (57.4%), exemestane (11.5%), anastrozole (9.8%). Median duration of RIB exposure was 100 d. Median time to first AE was 14 d. 83.6% pts experienced AEs with mild (63.9%) to moderate (50.8%) severity. Serious AEs were noted in 6.6% pts. Most common AEs were neutropenia (42.6%) and QTc prolongation (24.6%). 4.9% pts had hepatobiliary AEs. Due to AEs, dose adjustments (4.9%) and dose interruptions (19.8%) were needed. No deaths were reported; median PFS was not reached. Subgroup analysis by age ( < 65 y vs ≥65 y) showed that the incidence of AEs was 55.9% vs 44.1%. Neutropenia was reported in 46.4% pts aged < 65 y vs 39.3% pts aged ≥65 y; QT prolongation events were noted in 21.4% pts aged < 65 y vs 27.2% pts aged ≥65 y. Dose adjustments and dose interruptions were needed in 14.3% and 46.4% pts aged < 65 y vs 15.2% and 45.5% pts aged ≥65 y. Conclusions: Overall safety of RIB+AI in routine clinical practice in REACHAUT was consistent with that reported in the MONALEESA-2 study. In real-world setting, pt age ( < 65 y vs ≥65 y) had minimal impact on AEs. Clinical trial information: NIS006622.

553 Background: Dose-dense (DD) adjuvant chemotherapy improves outcomes in early breast cancer (BC). However, there are no data to inform on the combination of DD chemotherapy with trastuzumab for patients with HER2-positive disease. Methods: This is a protocol predefined secondary analysis of the randomized phase 3 PANTER trial. Women 65 years old or younger with node-positive or high-risk node negative BC were randomized 1:1 to either tailored according to hematologic nadirs and DD epirubicin/cyclophosphamide (4 cycles) followed by 4 cycles of docetaxel (tDD EC/D) or standard 3-weekly 5-fluorouracil/E/C (3 cycles) and D (3 cycles); Patients with HER2-positive disease received 1 year of adjuvant trastuzumab. In addition, HER2-positive and an equal number of matched for age, treatment group and institution, HER2-negative patients that were enrolled in Swedish sites were enrolled in a predefined study of cardiac safety and underwent echocardiography or MUGA and electrocardiography at baseline and at four and six years of follow-up. The primary endpoint was BC relapse-free survival (BCRFS). Results: There were 342 HER2-positive patients; 335 received at least one dose of trastuzumab, while 29 patients discontinued trastuzumab prematurely. BCRFS was not statistically significantly in favor of tDD EC/D (HR = 0.68, 95% CI 0.37 – 1.27, P= 0.231). Cardiac outcomes after four and six years of follow-up did not differ significantly between HER2-positive and HER2-negative patients, nor between tDD and standard treatment. Conclusions: To our knowledge, these are the only data on combining DD adjuvant chemotherapy and trastuzumab in BC. The combination decreased the risk for BC relapse by 32% compared to standard treatment, a statistically non-significant difference. Its efficacy and safety merit further evaluation as part of both escalation and de-escalation strategies. Clinical trial information: NCT00798070.

Purpose Anastrozole (ANA) alone delivers significant disease-free survival benefits over tamoxifen (TAM) monotherapy in postmenopausal women with early estrogen receptor–positive breast cancer. The ABCSG-8 (Austrian Breast and Colorectal Cancer Study Group 8) study is a large phase III clinical trial addressing the sequence strategy containing ANA in comparison with 5 years of TAM in a low- to intermediate-risk group of postmenopausal patients. Patients and Methods Endocrine receptor–positive patients with G1 or G2 tumors were eligible. After surgery, patients were randomly assigned to 5 years of TAM or 2 years of TAM followed by 3 years of ANA. Adjuvant chemotherapy and G3 and T4 tumors were exclusion criteria. Intention-to-treat and censored analyses of on-treatment recurrence-free survival (RFS) were performed, and exploratory survival end points and toxicity were investigated. Results Information from 3,714 patients, including 17,563 woman-years, with a median of 60 months of follow-up was available for this analysis. Median age was 63.8 years, 75% were node negative, and 75% had T1 tumors. Sequencing of ANA after identical 2-year treatment with TAM in both arms did not result in a statistically significant improvement of RFS (hazard ratio [HR], 0.80; 95% CI, 0.63 to 1.01; P = .06). Exploratory analyses of distant relapse-free survival indicated a 22% improvement (HR, 0.78; 95% CI, 0.60 to 1.00). On-treatment adverse events and serious adverse events were consistent with known toxicity profiles of ANA and TAM treatment. Conclusion Despite a low overall rate of recurrence in a population with breast cancer at limited risk of relapse, the a priori sequence strategy of 2 years of TAM followed by 3 years of ANA led to small outcome and toxicity benefits.

Purpose This randomized study compared denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor κ B (RANK) ligand, with zoledronic acid in delaying or preventing skeletal-related events (SREs) in patients with breast cancer with bone metastases. Patients and Methods Patients were randomly assigned to receive either subcutaneous denosumab 120 mg and intravenous placebo (n = 1,026) or intravenous zoledronic acid 4 mg adjusted for creatinine clearance and subcutaneous placebo (n = 1,020) every 4 weeks. All patients were strongly recommended to take daily calcium and vitamin D supplements. The primary end point was time to first on-study SRE (defined as pathologic fracture, radiation or surgery to bone, or spinal cord compression). Results Denosumab was superior to zoledronic acid in delaying time to first on-study SRE (hazard ratio, 0.82; 95% CI, 0.71 to 0.95; P = .01 superiority) and time to first and subsequent (multiple) on-study SREs (rate ratio, 0.77; 95% CI, 0.66 to 0.89; P = .001). Reduction in bone turnover markers was greater with denosumab. Overall survival, disease progression, and rates of adverse events (AEs) and serious AEs were similar between groups. An excess of renal AEs and acute-phase reactions occurred with zoledronic acid; hypocalcemia occurred more frequently with denosumab. Osteonecrosis of the jaw occurred infrequently (2.0%, denosumab; 1.4%, zoledronic acid; P = .39). Conclusion Denosumab was superior to zoledronic acid in delaying or preventing SREs in patients with breast cancer metastatic to bone and was generally well tolerated. With the convenience of a subcutaneous injection and no requirement for renal monitoring, denosumab represents a potential treatment option for patients with bone metastases.

538Background: Adjuvant breast cancer chemotherapy (ACT) improves relapse free (BCRFS) and overall survival (OS). Differences in terms of efficacy and toxicity could partly be explained by the sign...

500Background: Adjuvant aromatase inhibitors (AI) are standard of care for postmenopausal women with hormone receptor positive (HR+) early stage breast cancer but cause osteoporosis and fractures. ABCSG-18 showed previously that adjuvant denosumab significantly reduces clinical fractures (primary endpoint, HR = 0.5, p < 0.0001, Lancet 2015). Here, we present the impact of adjuvant denosumab on disease-free survival. Patients and Methods: 3,425 postmenopausal patients with early HR+ BC receiving adjuvant AI were recruited in 58 trial centers into this prospective, double-blind, placebo-controlled, phase-III trial. Patients were randomized 1:1 to receive either denosumab 60mg s.c. (N = 1712) or placebo (N = 1713) q6 months during AI therapy. We here present results of ABCSG-18’s secondary endpoint disease-free survival (DFS), including relevant subgroup and sensitivity analyses (accounting for cross-over either by censoring or by using a rank preserving structural failure time model). Results: After a media...

589Background: Achievement of complete or near complete pCR (RCB0/I) after neoadjuvant systemic therapy is associated with improved DFS. We have evaluated the utility of Ki67 measurements in predic...

e24175Background: The goal of this study was to evaluate and implement an NGS System, the GeneReader (Qiagen, Hilden, Germany) in a routine molecular laboratory, to compare its performance to other...

Purpose In human epidermal growth factor 2 (HER-2)–positive advanced breast cancer, taxanes or vinorelbine plus trastuzumab are among the most widely applied options in the first-line setting. We evaluated the efficacy and tolerability of capecitabine plus trastuzumab after anthracycline and docetaxel or vinorelbine failure and prior trastuzumab exposure. Patients and Methods Forty consecutive patients were included. Capecitabine was administered at a dose of 1,250 mg/m2 bid for 14 consecutive days in 3-week cycles, with dose modifications if necessary. Trastuzumab was administered every 3 weeks. Time to progression (TTP) was defined as primary end point. Response was evaluated every 3 months using International Union Against Cancer criteria. Results TTP was a median of 8 months, and overall survival was 24 months. No significant difference was found for second-line and beyond second-line treatment. A complete response (CR) was observed in 2.5%, partial response (PR) in 17.5%, stable disease lasting at least 6 months (SD) in 50%, resulting in a clinical benefit rate (CR + PR + SD ≥ 6 months) of 70%. Diarrhea (5%) and hand-foot syndrome (15%) were the only treatment-related adverse events that occurred with grade 3 or 4 intensity. Three patients (7.5%) developed brain metastases while receiving therapy. Conclusion Capecitabine plus trastuzumab appears to be an effective and safe option in a heavily pretreated population. Therefore, a direct comparison of this regimen with capecitabine monotherapy in this setting is warranted.

Purpose: To determine whether the addition of aminoglutethimide to tamoxifen is able to improve the outcome in postmenopausal patients with hormone receptor–positive, early-stage breast cancer. Patients and Methods: A total of 2,021 postmenopausal women were randomly assigned to receive either tamoxifen for 5 years alone or tamoxifen in combination with aminoglutethimide (500 mg/d) for the first 2 years of treatment. Tamoxifen was administered at 40 mg/d for the first 2 years and at 20 mg/d for 3 years. Results: All randomized and eligible patients were included in the analysis according to the intention-to-treat principle. After a median follow-up of 5.3 years, the 5-year disease-free survival in the aminoglutethimide plus tamoxifen group was 83.6% versus 83.7% in the monotherapy group (P = .89). The corresponding data for overall survival at 5 years were 91.4% and 91.2%, respectively (P = .74). More patients failed to complete combination treatment (13.7%) because of side effects as compared to tamoxifen alone (5.2%; P = .0001). Conclusion: Aminoglutethimide given for 2 years in addition to tamoxifen for 5 years does not improve the prognosis of postmenopausal patients with receptor-positive, lymph node-negative or lymph node-positive breast cancer.

PURPOSE: Effective adjuvant treatment modalities in premenopausal breast cancer patients today include chemotherapy, ovariectomy, and tamoxifen administration. The purpose of Austrian Breast and Colorectal Cancer Study Group Trial 5 was to compare the efficacy of a combination endocrine treatment with standard chemotherapy. PATIENTS AND METHODS: Assessable trial subjects (N = 1,034) presenting with hormone-responsive disease were randomized to receive either 3 years of goserelin plus 5 years of tamoxifen or six cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF). Stratification criteria included tumor stage and grade, number of involved nodes, type of surgery, and steroid hormone receptor content. Relapse-free survival (RFS) was defined as time from randomization to first relapse, local recurrence, or contralateral incidence, and overall survival (OS) as time to date of death. RESULTS: With a 60-month median follow-up, 17.2% of patients in the endocrine group and 20.8% undergoing chemotherapy developed relapses. Local recurrences emerged in 4.7% and 8.0%, respectively. RFS and local recurrence-free survival differed significantly in favor of endocrine therapy (P = .037 and P = .015), with a similar trend observed in OS (P = .195). CONCLUSION: Overall, our data suggest that the goserelin-tamoxifen combination is significantly more effective than CMF in the adjuvant treatment of premenopausal patients with stage I and II breast cancer.

e18151 Background: The ESMO-MCBS constitutes a new tool to quantify the clinical benefit that may be anticipated from a novel anticancer treatment based on original data from randomized or controlled trials. In contrast to comparable concepts, this score appears somehow unique as it concentrates on the clinical benefit for the individual patient irrespective of socioeconomic factors. Being introduced 2015; the MCBS has excited great public interest in Europe in the last year. We present here the first feasibility analysis of the MCBS under real-life conditions at the Medical University Vienna (MUV), one of Europe’s largest centers. Methods: This study evaluated systematically the practicability of the MCBS for advanced/metastatic malignant diseases treated at the MUV ( > 15 tumor entities). A 3-step approach including data analysis of regimens in regular use, assessment of scores (1 = not recommended to 5 = highly recommended) and evaluation of results with a focus on clinical feasibility was applied. Results: In the majority of tumor entities and clinical settings the assessed MCBS scores were consistent with our daily practice and particularly with our 1st line standards for common tumors like metastatic breast-, colorectal- or lung cancer. However, there were certain limitations including orphan diseases with a lack of randomized data (e.g. rare sarcoma subtypes) or tumor entities with cascade like treatment settings (e.g. colorectal cancer). Interestingly, new immunomodulatory approaches and checkpoint inhibitors in particular, scored strikingly high in comparison to conventional chemo due to a favorable toxicity profile, positive influence on quality of life and strong efficacy data in many cases. A broad selection of data will be presented at the meeting. Conclusions: Our analysis encompasses a wide range of tumor entities and clinical settings and reflects the daily experience of a university clinic. Mostly, the MCBS scores supported treatment decisions based on the clinical benefit to be expected from a novel therapy and might also support socioeconomic questions exemplified by high scoring of immunomodulatory approaches.

557 Background: The ABCSG 28 Posytive trial compared primary surgery versus primary systemic therapy without surgery in stage IV breast cancer patients. The primary aim was to investigate whether immediate resection of the primary tumor followed by standard systemic therapy improves median survival compared with no surgical resection (NCT01015625). The trial had to be stopped early due insufficient recruitment. Methods: Untreated stage IV breast cancer patients with the primary in situ were randomly assigned to either surgery of the primary versus no surgery followed by systemic therapy between 2011 and 2015 in 15 breast health centers in Austria. Systemic therapy included endocrine therapy or chemotherapy. Patients were routinely followed every 3-6 months. Primary endpoint was median survival. Results: 90 patients (45 with surgery, 45 with primary systemic therapy without surgery) were randomized. Stratification criteria were age, endocrine responsiveness, her2 expression, planned first line therapy and bone only versus other metastases. Patients in the surgery arm had more cT3 breast cancer (22% versus 7%) and more cN2 staging (16% versus 4%) as well as more her2 positive breast cancer cases (27% versus 18%). The median follow up was 37.5 months and immunohistochemical subtype analysis showed 9% basal like, 22% her2 positive, 51% luminal A and 13% luminal B cancers. Both groups were well balanced regarding first line treatment (endocrine versus chemotherapy) however, there were more taxane treated patients in the no surgery group (24.4 versus 15.6%). The median survival in the surgery arm was 34.6 months versus 54.8 months in the no surgery arm without statistical significance (HR 0.691 CI 0.358 – 1.333; p=0.267). Time to distant progression was insignificantly longer in the no surgery arm (surgery arm 13.9 versus no surgery arm 29.0 months). Conclusions: This first analysis of the prospective randomized phase III trial POSYTIVE-ABCSG-28 demonstrated no benefit in overall survival for immediate surgery of the primary in de novo stage IV breast cancer patients. Clinical trial information: NCT01015625.

1074 Background: The ABCSG 28 Posytive trial compared primary surgery versus primary systemic therapy without surgery in synchronous metastatic breast cancer. The primary aim of the study was to investigate whether immediate resection of the primary tumor followed by standard systemic therapy improves median survival compared with no surgical resection (NCT01015625). This report describes quality-of-life (QoL) results. Methods: Patients were randomized between 2011 and 2015. Patients completed the EORTC QLQ-C30 and EORTC QLQ-BR 23 before treatment and every 6 months during follow-up. Results: 90 patients (45 with surgery, 45 with primary systemic therapy without surgery) from 15 centers were included in the QoL analysis. At 6 months patients after surgery reported more insomnia, breast symptoms and arm symptoms than patients without surgery, but these differences were no longer present at later follow-up visits. In the univariate and multivariate analysis the global health status and physical functioning scales of EORTC QLQ C30 were statistically significant predictors for OS and TTP (p < 0.05). Over a 24-month follow-up, patients > 60 years showed more QoL impairments than those < 60 years, independent of treatment. Patients < 60 years had better physical functioning and less fatigue, appetite loss, constipation and breast symptoms than older patients. There were no differences in QoL between patients with bone metastases vs those with visceral ± bone metastases. Conclusions: In patients with primary metastatic breast cancer primary surgery does not appear to improve QoL. Global health status and physical functioning scales of EORTC QLQ-C30 appears to be a predictive factor for OS and TTP. Clinical trial information: NCT01015625.

PURPOSE A phase II study was performed to evaluate the antitumor activity and toxicity of irinotecan (CPT-11), a water-soluble derivative of camptothecin, in patients with prior chemotherapy-treated squamous cell cancer of the cervix. PATIENTS AND METHODS Forty-two patients were included in the study. The median age was 44 years (range, 24 to 59 years). The median Zubrod performance status was 1. All patients were refractory to first-line chemotherapy and 88% had received prior radiotherapy. The initial dose of CPT-11 was 125 mg/m2 given as a weekly 90-minute intravenous infusion for 4 weeks, every 6 weeks. Subsequent doses were unchanged, reduced, or omitted according to toxicity grade. RESULTS Forty-two patients were assessable for response. The overall response rate was 21%. The median time to response was 6 weeks and the median duration of response was 12 weeks. The overall median duration of survival was 6.4 months. A statistically significant survival advantage (median of 12.6 v 5.1 months) was found in patients whose disease responded to the treatment (P < .015). The major dose-limiting toxic effects (grade > or = 3) were nausea and vomiting (45%), diarrhea (24%), and granulocytopenia (36%). Grade > or = 3 anemia was encountered in 62% of patients and the incidence of thrombocytopenia was negligible. Less severe side effects were alopecia (48%), drug fever (43%), anorexia (33%), fatigue (33%), skin rash (21%), stomatitis (14%), and allergic reaction (9%). The gastrointestinal intolerance was dose-related. The incidence of bone marrow depression did not decrease with dose reduction, possibly because of a cumulative effect or hematologic intolerance by a subset of patients. CONCLUSIONS CPT-11 has significant activity in refractory cervical carcinoma. Gastrointestinal intolerance and hematologic toxicity must be monitored carefully. Further studies of alternative schedules may improve the tolerance and response rate.

e20613Background: Activating mutations in the epidermal growth factor receptor (EGFR) gene are pharmacological targets for EGFR tyrosine kinase inhibitors (TKI) in patients with advanced non-small-...

1002Background: Standard dosing of chemotherapy (ct) based on body surface area results in marked inter-patient variation in pharmacokinetics, toxicities and efficacy. Methods: 2,017 patients with node-positive or high-risk node-negative breast cancer were randomized (1:1) in 86 centers in Sweden, Austria and Germany between February 2007 and September 2011 to either four cycles of leukocyte nadir-based tailored and dose-dense adjuvant epirubicin (E) 38-120 mg/m 2, start at 90 mg/m 2) and cyclophosphamide (C) 450-1200 mg/m 2, start at 600 mg/m 2) Q2W, followed by four cycles of docetaxel (D) 75-100 mg/m 2, start at 75 mg/m 2) Q2W (three weeks pause between EC and D) (tdd arm) or three cycles of standard 5-Fluorouracil (F) 500 E100 C500 Q3W followed by three cycles of D100 Q3W (control arm). Total treatment duration was the same in the two arms. The primary endpoint was breast cancer relapse-free survival (BCRFS) assessed in the intention to treat population. Secondary endpoints included event-free surviva...

e20536 Background: We aimed to analyze the impact of BC subtypes on the clinical course with special emphasis on the occurrence of brain metastases (BM) and outcome in an elderly breast cancer popu...

504 Background: Adjuvant endocrine therapy compromises bone health in pre- and postmenopausal breast cancer (BC) patients. Treatment-induced osteopenia, osteoporosis, and fractures are frequent sid...

463 Background: Addition of nab-paclitaxel to gemcitabine has recently been demonstrated in the clinical phase III trial MPACT to be beneficial for progression free survival, overall response rate, and overall survival in advanced pancreatic cancer patients. Any potential biologic activity of nab-paclitaxel in biliary cancer is hitherto unknown. Methods: A retrospective analysis of patients with advanced biliary cancer was undertaken to determine the disease control rate (CR+PR+SD), progression-free survival and overall survival in patients who had received nab-paclitaxel-based chemotherapy after failure of a platinum-containing first-line combination chemotherapy. Results: Eleven patients were identified. 4 of 11 patients received nab-paclitaxel as second line, 7 of 11 patients as a third-line treatment. 7 of 11 patients received nab-paclitaxel in combination with gemcitabine, while in 4 of 11 patients nab-paclitaxel was combined with fluoropyrimidine. The disease control rate seen with nab-paclitaxel was 81% (nine of eleven patients). Disease was progressive in one patient, and in one patient the response status is unknown yet. One patient received partial remission and 8 patients had stable disease. As of September 13th, 2014, three patients are still undergoing nab-paclitaxel combination therapy, but were censored by this date for analysis. The median time to progression was 4.9 months (2.3 – 18.9 months) for all patients (11/11 pts.), and 9.5 months for patients completed nab-paclitaxel treatment (8/11 pts.). Median overall survival for all eleven patients after initiation of nab-paclitaxel treatment was 7.3 month (2.6 – 21.8 month). The mean time of survival after diagnosis of advanced disease was 21.3 month, whereby 5 patients were alive at date of censoring. Conclusions: Nab-paclitaxel based chemotherapy can be an effective second-line regimen after platinum-failure in patients with advanced biliary cancer. In this small series, nab-paclitaxel appears to have a biological activity by controlling the disease and positively affecting survival. Randomized trials in this group of patients are urged.