1877 Everolimus in heavily pre-treated metastatic breast cancer (MBC): Is real (developing) world experience different?

S292 A total of 74 patients (38 untreated and 36 pretreated) were analyzed for safety. One serious adverse event (ischemic heart attack) was reported. In untreated and pretreated group grade 1−2 included nausea (45% and 30%) leucopenia (26% and 22%) increased of liver enzymes (29% and 39%) hand and foot syndrome (24% and 19%). Grade 3 toxicities (hand and foot syndrome, hematologic and liver toxicities) were reported in 5% and 3% untreated and pretreated patients respectively. No patient experienced grade 4 toxicities. Conclusions: The VEX combination have good tolerability with high activity in metastatic breast cancer patients with hormonal receptor positive disease. No conflict of interest. 1877 POSTER Everolimus in heavily pre-treated metastatic breast cancer (MBC): Is real (developing) world experience different? J. Bajpai1 , A. Ramaswamy1 , J. Ghosh1 , S. Gulia1 , S. Gupta1 . 1 Tata Memorial Hospital, Medical Oncology, Mumbai, India Background: Resistance to endocrine therapy (ET) in MBC is associated with activation of the mammalian target of rapamycin (mTOR) intracellular signalling pathway and its inhibition by everolimus with ET has proven efficacy in phase III randomized trials from west. However, there is lack of data from Asian subcontinent especially in real world scenario and merits exploration. Methods: A retrospective analysis of everolimus in hormone receptor (HR) positive MBC who had recurrence or progression while receiving previous therapy with aromatase inhibitor (AI) in MBC was conducted from March 2012 to June 2014. Response rates, and toxicity was recorded as per the standard criteria and progression-free survival (PFS) was calculated by the Kaplan–Meier method. Results: There were 41 patients with a median age of 55 years. 73% had visceral metastasis.Among those, 73% patients had 2 sites of metastases, commonest being bone (73%) followed by lungs(50%). Thirty (73%) patients had prior 3 lines of therapy including AI(100%), tamoxifen(94%), Fulvestrant (39%) and chemotherapy(100%). Majority had progressed after a short PFS on immediate preceding therapy, including 13 (32%) within 3 months, 8(20%) within 6 months.The commonest grade 3/4 adverse events were stomatitis(19%), hyperglycemia (new/worsening, 17%), fatigue (14.5%), Non Neutropenic (including atypical) Infections (14%), anemia (12%) and pneumonitis (7.%). Dose reductions were required in 31%. Neutropenia (without Febrile neutropenia) was seen in 10%. For a Clinical Benefit Rate of 68%, there were 30% PRs, 38% SD, 32% PDs. Everolimus was active in all subgroups.The median PFS was 21.6 (3−76) weeks. Conclusions: Everolimus and ET is an efficacious treatment option in heavily pre-treated HR positive MBC’s with meaningful clinical benefit. Pharmacogenomic differences could be the reason for different dose requirement with atypical toxicity profile, especially high incidence of atypical infections suggest immunsuppresent potential and merits exploration in a larger prospective cohort. No conflict of interest. 1878 POSTER Patient stratification of high risk HER2-/HR+ patients following aromatase inhibitor (AI) therapy L. Mitrofan1 , C. Gajperia2 , J. Charnock2 , C. Anger2 . 1 IMS Health, Oncology, Paris, France; 2 IMS Health, Oncology, London, United Kingdom Background: Endocrine therapies such as tamoxifen, fulvestrant and aromatase inhibitors (AI) are the standard treatment options for estrogens receptor-positive (ER+) breast cancer patients. Intrinsic and acquired resistance is common and many tumours will recur or progress despite these treatments. The resistant phenotype is characterized by aberrant expression of cyclin D1, estrogen regulation, increased activity of transcription factors. Therefore, the clinical need to accurately identify high risk patients and combat resistance represents a major challenge. Using real world data, we are able to identify high risk patients after AI treatment and map out of their following treatments. Material and Methods: This study used IMS Oncology Analyzer™, an anonymised patient database collected through quarterly physician panel survey, which provides comprehensive insight into total cancer care. Data collected between October 2013 and September 2014 was used to profile treated patients in terms of reason for stopping their previous AI therapy,

Abstracts treatments choices after AI and consequent treatment progression interval between AI and subsequent treatments type. Results: The MAT Q3 2014 dataset includes 1,133 currently treated mBC patients with HER2-/HR+ status (18% UK, 20% Germany, 17% Spain, 24% Italy and 21% France). For patients previously treated with an AI, 60% ceased their AI therapy due to distant progression most probably due to developing acquired resistance. 22% of these patients were retreated with an AI. The majority of AI retreatment was with exemestane as per current guidelines. The remaining 78% went onto receive other treatments, including other hormonal therapies (40%) or cytotoxic therapies (38%). The most common hormonal therapy is fulvestrant monotherapy (70%) and the most common cytotoxic therapy in the form of bevacuzimab+paclitaxel (27%). In addition, 85% of patients progressed from their AI treatment to their subsequent treatment within 12 months, while the treatment progression interval exceeded 12 months only for 15% of patients. Conclusions: This study has identified a cohort of high risk HER2/HR+ patients who have previously progressed from an AI therapy and which represents an unmet clinical need. To overcome their AI acquired resistance, these patients switched to alternative estrogen therapies (fulvestrant), AI (exemstane) or chemotherapy (BEVA/PAC). Promising PFS results from current phase III clinical trials involving CDK inhibitors in combination with an AI, represents today one of the best treatment solutions for this specific high risk patient segment. No conflict of interest. 1879 POSTER Impact of adjuvant trastuzumab (adjT) for early-stage (ES) breast cancer (BC) on clinical characteristics, survival and likelihood of durable complete response (DCR) of HER2-positive (HER2+) metastatic breast cancer (MBC): A 15-year single-institution cohort study A. Zacchia1 , G. Gullo1 , I. Parker2 , A. De Giorgi1 , D. Fennelly1 , D. Zanoni1 , J. Walshe1 , A.M. Defrein3 , C. Quinn4 , N. Silva5 , N. O’ Donovan6 , J. Ballot7 , E. Mc Dermott8 , J. Crown1 . 1 St Vincent’s University Hospital, Medical Oncology, Dublin, Ireland; 2 ICORG, Medical Statistics, Dublin, Ireland; 3 St Vincent’s University Hospital, Oncology Pharmacy, Dublin, Ireland; 4 St Vincent’s University Hospital, Pathology, Dublin, Ireland; 5 St Vincent’s Private Hospital, Oncology Pharmacy, Dublin, Ireland; 6 National Institute of Cellular Biotechnology, Translational Oncology, Dublin, Ireland; 7 St Vincent’s University Hospital, Oncology Clinical Research Unit, Dublin, Ireland; 8 St Vincent’s University Hospital, Breast Surgery, Dublin, Ireland Background: In this study we report the changes which have occurred in the clinical features and outcome of patients (pts) with MBC as a result of adjT (including neoAdj) for ESBC. Materials and Methods: We collected data on all 742 pts treated with T for HER2+ BC in our institution since 2000. The data base included pts treated with T for MBC (since 2000), adjT for ESBC (on clinical trials between 2001 and 2004 and routinely since 2005). In this study we focus on MBC, and report the incidence of de novo (DN) versus relapsed (R) MBC, Complete Responses (CR) and survival data for DN vs R, and across 3 sequential five year time cohorts. Results: A total of 224 pts treated with T for MBC between January 2000 and December 2014 were identified. Pts were subdivided into 3 cohorts of 5 years: Cohort 1 (Jan 2000 − Dec 2004 N = 67), Cohort 2 (Jan 2005 − Dec 2009 N = 85), Cohort 3 (Jan 2010 − Dec 2014 N = 72). The proportion of pts with R MBC decreased across the 3 cohorts (I-84% vs II-64% vs III-57%) whereas the proportion of DN MBC has increased (I16%vs II-36%vs III-43%) [p < 0.01]. DN pts had significantly longer median OS (58m, [95% CI: 26−90]) compared to R pts (29m [95% CI: 21−37]), p < 0.001 log rank. Median OS improved from Cohort 1 to Cohort 3. Best Objective Response (OR) to antiHER2 therapy was evaluable on 214 pts and assessed specifically for the present study. OR was defined as Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD) according to RECIST 1.0 criteria. In all Cohorts OR significantly predicted median OS [95% CI]: CR 163 [92–234], PR/SD 41 [36−46], PD 16 [11−21] months [p < 0.001]. CR was obtained in 31pts (14%), 21 of whom never relapsed. In multi-variate analysis, DN MBC and single site of MBC (excluding bone-only disease) statistically significantly predicted the likelihood of achieving CR. Estimated median OS of CR pts treated before 2005 is 128mos [95% CI: 46–210] but is un-estimable (median not reached) for pts treated after 2005. Conclusions: (1) The introduction of adjT for ESBC has substantially changed the clinical characteristics of HER2+ MBC, with a marked increase in the proportion of pts diagnosed with DN. (2) DN pts have significantly superior OS compared to R pts. (3) Durable CR is significantly more common in pts with DN and with non-bone single site of MBC. (4) Survival