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The sodium-glucose cotransporter 2 inhibitors (SGLT2i) empagliflozin, canagliflozin, and dapagliflozin reduce the risk of heart failure (HF) events in patients with diabetes mellitus (DM) at high risk for HF. Differences in HF outcomes between SGLT2i were demonstrated in a recent-published meta-analysis. Nevertheless, comparative cost-effectiveness analyses of SGLT2i provided for this indication have not been published yet. Therefore, we aimed to provide a preceding economic comparison of the costs required for improving HF outcomes by these three SGLT2i. The primary outcome was the cost needed to treat (CNT) to prevent one event of hospitalization for HF or cardiovascular mortality. CNT is calculated by multiplying the annualized number needed to treat to prevent one event by the annual cost of therapy. Clinical outcome data were extracted from pre-specified cohorts of HF-naive patients in the pivotal randomized controlled trials (RCTs). Costs of interventions were estimated as 75% of the US National Average Drug Acquisition Cost listing. Sensitivity analysis was performed to mitigate differences between the RCT's populations. We figured the CNT for the primary prevention of HF events in DM patients to be $542,328 ($409,044-$905,412) for empagliflozin, $2,347,488 ($1,066,208-∞) for canagliflozin and $2,128,374 ($1,204,740-$48,140,518) for dapagliflozin. Sensitivity analysis confirmed the cost benefit of empagliflozin. Our findings suggest that between the available SGLT2i, the cost of primary prevention of HF in patients with DM at high risk for HF is lowest with empagliflozin. These findings may help choose an SGLT2i until head-to-head RCTs, and comprehensive cost-effective analyses for this indication are available.

Introduction: The Glucagon-Like Peptide-1 receptor agonists (GLP-1a) semaglutide, dulaglutide, and liraglutide reduce major adverse cardiovascular events (MACE) in patients with Type 2 diabetes mellitus ( T2DM) and established CVD. The American Diabetes Association currently recommends providing GLP-1a therapy to this patient population independently of glycaemic control. Despite proven clinical benefits, providing GLP-1a to all guideline eligible patients is a significant cost burden on healthcare systems. Therefore, it is imperative to compare the value for money of these agents. Hypothesis: The newly introduced GLP-1a Semaglutide may be cost-saving compared to dulaglutide and liraglutide for preventing MACE in patients with established CVD and T2DM. Methods: We calculated the cost needed to prevent one MACE, by multiplying the annualized number needed to treat to prevent one event, by the annual cost of the therapy. Efficacy estimates were extracted from published RCT data. We performed a sensitivity analysis to mitigate differences between trial populations and other uncertainties. Drug costs were based on published US prices. Results: The cost needed to prevent one MACE with semaglutide is $557,187 ($331,491-$2,194,483) compared to $1,179,360 ($732,888-$2,746,224) with liraglutide and $1,605,904 ($706,044-∞) for dulaglutide. Sensitivity analysis confirmed the advantage of semaglutide. Conclusions: Semaglutide prescribed for secondary prevention of MACE in patients with T2DM and established CVD seems to provide more value for money than dulaglutide and liraglutide for the same purpose.

Background In the U.S., the addition of bevacizumab to first-line chemotherapy in metastatic colorectal cancer (mCRC) has been demonstrated to provide 0.10 quality-adjusted life years (QALYs) at an incremental cost-effectiveness ratio (ICER) of $571,000/QALY. Due to variability in pricing, value for money may be different in other countries. Our objective was to establish the cost-effectiveness of bevacizumab in mCRC in the U.S., U.K., Canada, Australia, and Israel. Methods We performed the analysis using a previously established Markov model for mCRC. Input data for efficacy, adverse events, and quality of life were considered to be generalizable and therefore identical for all countries. We used country-specific prices for medications, administration, and other health service costs. All costs were converted from local currency to U.S. dollars at the exchange rates in March 2016. We conducted one-way and probabilistic sensitivity analyses (PSA) to assess the model robustness across parameter uncertainties. Results Base case results demonstrated that the highest ICER was in the U.S. ($571,000/QALY) and the lowest was in Australia ($277,000/QALY). In Canada, the U.K., and Israel, ICERs ranged between $351,000 and $358,000 per QALY. PSA demonstrated 0% likelihood of bevacizumab being cost-effective in any country at a willingness to pay threshold of $150,000 per QALY. Conclusion The addition of bevacizumab to first-line chemotherapy for mCRC consistently fails to be cost-effective in all five countries. There are large differences in cost-effectiveness between countries. This study provides a framework for analyzing the value of a cancer drug from the perspectives of multiple international payers.

Evolocumab and ezetimibe, were both proven to significantly reduce the incidence of major adverse cardiovascular events (MACE), in type 2 diabetes patients with atherosclerotic cardiovascular disease and low-density lipoprotein (LDL) cholesterol >70 mg/dl despite statin therapy. Providing evolocumab for all such patients may be a significant burden on healthcare systems. Therefore, we analyzed the treatment cost of ezetimibe versus evolocumab to prevent 1 MACE. We extracted the number needed to treat (NNT) with evolocumab or with ezetimibe for avoiding MACE from the published FOURIER and IMPROVE-IT trials respectively. Drug costs were based on 2018 US prices. Sensitivity and scenario analyses were performed to overcome variances in terms of population risk, efficacy of therapies, and costs. In FOURIER, the 1-year NNT for avoiding MACE with evolocumab was 104 (95% confidence intervals [CI] 66 to 235). In IMPROVE-IT, the 1-year NNT with ezetimibe was 124 (95% CI 73 to 288). The annual cost of evolocumab and ezetimibe is $6,540 and $88, respectively. Therefore, the cost to prevent 1 MACE in the FOURIER and IMPROVE-IT trials would have been $678,981 (95% CI $429,810 to $1,537,910,149) and $10,870 (95% CI $6,384 to $25,322), respectively. Ezetimibe was consistently a cost-saving strategy compared with evolocumab, in all analyses performed, except for the case where evolocumab price is significantly reduced and the branded ezetimibe is used. In conclusion, treatment with ezetimibe seems to be a major cost-saving strategy for preventing MACE in this patient population.

Empagliflozin, an inhibitor of sodium-glucose cotransporter 2 and Liraglutide, a glucagon-like peptide 1 analogue, were both proved to significantly reduce the incidence of cardiovascular (CV) death in patients with type 2 diabetes and established CV disease. However, addition of either drug to current diabetes treatment regimens may impose a significant burden on healthcare systems. We performed a cost-minimization analysis of Empagliflozin versus Liraglutide for preventing CV death. Rates of prevention of CV death were extracted from the published data of the EMPA-REG OUTCOME and LEADER trials. Drug costs were extracted from the US National Average Drug Acquisition Costs of 2017. In the EMPA-REG OUTCOME trial 5,833 patient-years of treatment with Empagliflozin resulted in the prevention of 51 CV deaths. In LEADER, 16,338 patient-years of Liraglutide resulted in the prevention of 59 CV deaths. The price in 2017 of annual Empagliflozin and Liraglutide therapy was $4,980 and $9,300, respectively. Therefore, the cost of Empagliflozin or Liraglutide needed to prevent 1 CV death would be $569,526 (95% confidence interval $415,713 to $921,798) and $2,575,312 (95% confidence interval $1,607,526 to $7,807,986), respectively. In conclusion, use of Empagliflozin for preventing CV death in type 2 diabetes patients with an established CV disease seems to be a major cost-saving strategy compared with Liraglutide. These results should be considered in the context of other individual drug and patient factors.

After a decade of extensive use, the actual contribution of bevacizumab in first-line treatment of metastatic colorectal cancer (mCRC) is still unclear.To evaluate 'real-life' outcomes of patients with mCRC before and after the introduction of bevacizumab to standard mCRC first-line practice.Using the computerized administrative database of Clalit Health Services' (CHS), Israel's largest health care provider, we retrospectively compared two cohorts (n = 1739): (A) all CHS' patients diagnosed with mCRC between January 2000 and December 2004 that received first-line irinotecan or oxaliplatin-based combination chemotherapy (before bevacizumab was introduced) (n = 1052), and (B) all patients that started first-line irinotecan or oxaliplatin combination chemotherapy together with bevacizumab between September 2006 and December 2009 (after bevacizumab was fully reimbursed in Israel for mCRC first-line therapy) (n = 687). The primary endpoint was overall survival (OS) and secondary endpoints were first-line progression-free survival (PFS) and metastatectomy rates.Median OS was longer in Cohort B than in Cohort A [23.0 months vs.15.0, adjusted hazard ratio (HR), 0.75]. Secondary outcomes were also better; PFS of 14.0 months vs. 9.8 in the earlier period (HR, 0.75) and metastatectomy rate of 8.1% versus 3.9%. The longer OS in Cohort B was preserved even after controlling for latter-line epidermal growth factor receptor (EGFR) inhibitor use (HR = 0.77).In this analysis, OS, PFS and metastatectomy rates of first-line treatment of mCRC were significantly higher in the later period of the study. These results, derived from 'real-life' practice, suggest that the use of bevacizumab, among other alterations in the clinical management of mCRC between the two periods, might have had a significant contribution to these outcomes, and may therefore support the current practice of adding bevacizumab to first-line treatment of mCRC.

Background: The angiotensin receptor-neprilysin inhibitor sacubitril/valsartan has been shown in the PARADIGM-HF trial to be superior to enalapril in reducing the risks of cardiovascular (CV) deaths and hospitalizations in heart failure (HF) patients. Although several studies suggested that sacubitril/valsartan is a cost-effective therapy, budget constraints may limit its use. Our objective was to characterize HF sub-populations in which cost per CV death/hospitalization prevented are excessively high in order to assist in treatment prioritization decisions. Methods: Outcome data were retrieved from the published PARADIGM-HF trial reports. Costs were calculated based on current United States prices of sacubitril/valsartan. Results: In the PARADIGM-HF trial, treatment of 4,187 patients with sacubitril/valsartan resulted in prevention of 203 CV deaths or HF hospitalizations (135 CV deaths) during a total of 9,396 patient-years. The estimated additional cost of sacubitril/valsartan during the trial’s follow-up period would have reached $42,089,220. Therefore, the cost of preventing one HF hospitalization or CV death would have been $207,336 and the cost of preventing one CV death would have been $311,772. This figure is significantly higher in sub-groups that presented a lower risk-reduction, as in patients with an ejection fraction >35% ($674,831) and in patients without prior use of HF medical therapy ($2,024,494). Conclusions: In healthcare settings under budget constraints, payers can maximize clinical outcomes in HF patients, by prioritizing sacubitril/valsartan therapy to sub-populations that have demonstrated higher benefit in the PARADIGM-HF trial. Advocating the reduction of sacubitril/valsartan prices could enable wider populations to benefit from this promising therapy.

Backgound Randomized controlled trials (RCTs) have shown that dabigatran, rivaroxaban and warfarin cause similar bleeding rates. Methods We performed a retrospective population-based cohort study to determine the incidence of bleeding in patients with atrial fibrillation (AF) beginning dabigatran, rivaroxaban or warfarin. Consecutive patients initiating anticoagulation for AF during a 3 year period were identified using a computerized database. Patients who bled and required hospitalization underwent chart review. Bleeding incidences were calculated per 100 patient-years of treatment. Results 18,249 patients were included: 9564 (52.4%) received warfarin, 5976 (32.7%) dabigatran, and 2709 (14.8%) rivaroxaban. Bleeding incidences were 3.9 (95% CI, 3.6–4.4) in warfarin-treated patients, 4.2 (95% CI, 3.7–4.7) in dabigatran patients, and 4.1 (95% CI, 3.0–5.3) in rivaroxaban patients. Intracranial hemorrhage (ICH) rates were 0.71 (95% CI, 0.56–0.90) for warfarin, 0.4 (95% CI, 0.18–0.87) for dabigatran, and 0.27 (95%CI, 0.10–0.80) for rivaroxaban. GI hemorrhage rates were 1.88 (95%CI, 1.62–2.20) for warfarin, 2.98 (95% CI, 2.4–3.5) for dabigatran and 2.39 (95%CI, 1.6–3.5) for rivaroxaban. Conclusions We demonstrate similar bleeding rates with both dabigatran 150 mg and 110 mg and rivaroxaban compared to warfarin.

Importance The risk for herpes zoster (HZ) in patients with psoriasis treated with biologic medications or other systemic treatments has been given little attention to date. Objective To describe the risk for HZ in patients with psoriasis and its relation to treatment. Design, Setting, and Participants A cohort study was performed using the administrative database of Clalit Health Services, the largest public health care provider organization in Israel, in the setting of general community clinics, primary care and referral centers, and ambulatory and hospitalized care. We extracted information for all patients who received a psoriasis diagnosis from January 2002 to June 2013. Follow-up was conducted until the end of July 2013. The study included 95 941 patients with psoriasis in the analysis, with 522 616 person-years of follow-up. Incidence of HZ events was calculated for each systemic antipsoriatic medication provided, during a follow-up period of 11 years and 7 months. We used a generalized estimating equation Poisson regression model to examine the effect of each systemic treatment for psoriasis on HZ incidence, adjusting for age, sex, psoriasis severity, Charlson comorbidity index, steroid treatment, and socioeconomic status. Main Outcomes and Measures Incidence of HZ associated with systemic therapies. Results In a multivariate analysis, it was observed that treatment with phototherapy (rate ratio [RR], 1.09 [95% CI, 0.62-1.93]; P = .99), methotrexate (RR, 0.98 [95% CI, 0.78-1.23]; P = .83), cyclosporine (RR, 1.16 [95% CI, 0.48-2.80]; P = .49), and biologic medications as a single agent (RR, 2.67 [95% CI, 0.69-10.3]; P = .14) was not associated with HZ. The use of combination treatment with biologic medications and methotrexate was significantly associated with an increased incidence of HZ (RR, 1.66 [95% CI, 1.08-2.57]; P = .02). The use of acitritin was associated with decreased incidence of HZ (RR, 0.69 [95% CI, 0.49-0.97]; P = .004). Conclusions and Relevance Physicians may need to consider offering an HZ preventive vaccine to patients receiving combination treatment with biologic medications and methotrexate, particularly if they have additional risk factors for HZ.

Background The relative efficacy of lapatinib vs. continuing trastuzumab beyond progression (TBP) in HER2-positive metastatic breast cancer (MBC) patients, who progressed on first-line trastuzumab, is still unclear. The objective of this population based cohort study was to compare outcomes of lapatinib vs. TBP in daily practice. Methods All HER2-positive MBC patients who began second-line anti HER2 therapy between 1st January 2010 and 30th August 2013 were selected from Clalit Health Services’ (CHS) electronic database. Available data on patient and disease characteristics and treatments were analyzed. The primary endpoint was overall survival (OS). Outcomes were compared using the Kaplan-Meier (log-rank) method and Cox proportional hazards model. Results 64 patients received second-line lapatinib and 93 TBP. The two treatment groups were similar in age and co-morbidity rates, but differed in proportion of prior adjuvant trastuzumab (lapatinib: 29.7%, TBP: 16.1%, P = 0.043) and rates of prior brain metastases (lapatinib: 32.8%, TBP: 10.8%, P = 0.01). Lapatinib median OS was 13.0 months (95% CI: 9.5–16.5) vs. 31.0 for TBP (95% CI: 20.6–41.4), P

e12512 Background: Tumors with HER2 overexpression usually respond to HER2-targeted therapies. Since the CLEOPATRA and EMILIA trials, a taxane plus trastuzumab and pertuzumab (TTP) are the first-line standard for the management of HER2 + metastatic breast cancer (MBC) and trastuzumab emtansine (TDM-1) is the second-line standard. Intrinsic subtypes existing within HER2+ tumors may impact the degree of a patient’s response to anti HER2 therapy; however HER2 subtyping for predicting response is still experimental and not in routine clinical use. In this retrospective population-based study, we aimed to assess whether duration of treatment (DOT) of second-line TDM1 is associated with the DOT of first-line TTP, and might serve as a hint for a HER2 subtype. Methods: Clalit Health Services (CHS) manages health care of 52% of the Israeli population. We identified 113 HER2+ CHS MBC patients, treated with TTP as first-line treatment that initiated TDM1 as second-line, until Dec. 31, 2016. Patient's (pts) demography, HER2 and HR status were recorded. A Cox proportional hazard model, stratified by HR status, adjusted for age and prior adjuvant trastuzumab, was used to explore the association between second-line and first-line DOT in HR positive and negative pts. Results: Pts baseline characteristics and DOT in first- and second-line treatment are presented in the table. A statistically significant association between DOT of both treatment lines was found in HR positive pts with a trend also in HR negative pts. Conclusions: The observed association between first- and second-line DOT, unrelated to hormonal status, may result from a primary characteristic of the intrinsic tumor subtype, that impacts acquired resistance. Longer observations in larger patient cohorts are required to confirm this observation. [Table: see text]

INTRODUCTION Recent large randomized controlled trials have shown that direct oral anticoagulants (DOACs) are at least as effective as vitamin K antagonists (VKAs) for prevention of stroke or systemic embolism in patients with non-valvular atrial fibrillation (AF) and are associated with similar or lower rates of bleeding. The results for bleeding seen in Phase 3 trials might not be applicable to real world practice. Population-based studies suggest that the bleeding risk for DOACs and VKA is similar however neither the risk of bleeding associated with different doses of DOACs nor that associated with apixaban in routine clinical practice is well established. We performed a large population-based study to determine the incidence of bleeding in patients with AF beginning treatment with different doses of dabigatran, rivaroxaban, apixaban or a VKA. METHODS From the computerized database of the 4.5 million member Israeli Clalit Health Services health care provider, consecutive patients initiating a VKA or DOAC for AF between January 1, 2011 and December 31, 2014 were studied. Bleeding patients who required hospitalization were identified and key clinical and laboratory data were recorded. Incidence of bleeding was calculated during the first 20 months of treatment which was the minimum duration of treatment for all of the drugs. Adjusted hazard ratios for overall bleeding, intracranial hemorrhage (ICH) and gastrointestinal (GI) bleeding and all-cause mortality within 30 days were recorded and case fatality rates were calculated as the proportions of bleeding patients who died within 30 days. RESULTS 26184 patients initiated anticoagulants for AF: 14258 received VKA, 214 -received dabigatran 75 mg, 3563 received dabigatran 110 mg , 1410 received dabigatran 150 mg, 2570 received rivaroxaban 15 mg, 2140 received rivaroxaban 20 mg, 1227 received apixaban 2.5 mg and 802 received apixaban 5 mg. Key patient demographics and the overall and site-specific bleeding rates are shown in table 1. Hazard ratios for any bleeding, ICH and GI bleeding adjusted for age, renal failure, CHADS2 score, aspirin use and Charlson comorbidity score favored dabigatran 150 mg versus VKA (P CONCLUSIONS The results of our population-based non-randomized study of unselected AF patients demonstrate a decreased bleeding rate for dabigatran 150mg and an increased bleeding rate for apixaban 2.5 mg compared to VKA. There was a consistent tendency for increased bleeding in patients receiving lower versus higher doses of the NOACs which probably reflects physician tendency to select lower doses of DOACs for patients at greater risk for bleeding. Disclosures Ellis: Boehringer Ingelheim: Speakers Bureau; Bayer: Speakers Bureau; Pfizer: Speakers Bureau. Eikelboom:Pfizer: Honoraria, Research Funding; Eli Lilly: Honoraria, Research Funding; Boehringer Ingelheim: Honoraria, Research Funding; Daiichi-Sankyo: Honoraria, Research Funding; Bayer: Honoraria, Research Funding; Astra Zeneca: Honoraria, Research Funding; Bristol Myer Squibb: Honoraria, Research Funding; Sanofi-Aventis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding.

6518Background: In the United States, the addition of bev to 1st-line chemotherapy in mCRC provides an additional 0.10 quality-adjusted life years (QALYs) at an incremental cost-effectiveness ratio (ICER) of $571,240/QALY (Goldstein et al. Journal of Clinical Oncology, 2015). However, this estimate of value is not transferrable between countries due to variable international pricing strategies. Our objective was to establish the cost-effectiveness of bev in mCRC in 5 different countries: the US, the UK, Canada (CAN), Australia (AUS), and Israel (ISR). Methods: We performed the analysis on the basis of a previously published Markov model (Goldstein et al. JCO, 2015). Input data for efficacy, adverse events and quality of life were considered to be standard for all countries. We used country specific prices for all healthcare services, medications, and administration costs. For the UK, all costs were obtained from UK Department of Health, National Health Service and British National Formulary. For CAN, all ...

539 Background: Based on a single phase 3 study, the mTOR inhibitor tem was approved as 1st line therapy for prmRCC. However, in daily practice, prmRCC pts are often treated with the VEGFR and PDGFR inhibitor su. We aimed to compare the clinical effectiveness of su vs tem in prmRCC pts. Methods: We performed an international multicenter retrospective study of pts with prmRCC (HENG criteria), who were treated in 8 centers across 2 different countries. 31 pts were treated with 1st line tem. Each tem treated pt was individually matched with a 1st line su treated pt, by clinicopathologic factors. The effect of tx type (tem vs su) on clinical benefit, progression free survival (PFS) and overall survival (OS), was tested using a chi-square test and partial likelihood test from cox model. Furthermore, univariate and multivariate analyses of association between clinicopathologic factors and tx type (tem vs su), and outcome were performed using the entire pt cohort (n=62). Results: The groups were matched by age (median 65), gender (male 68%), prior nephrectomy (58%), renal cell carcinoma histology (clear cell 81%), smoking status (active in 35%), use of angiotensin system inhibitors (42%), and pre-tx neutrophil to lymphocyte ratio >3 (58%). In tem vs su treated pts, clinical benefit (partial response + stable disease) was 61% (n=19) (partial response 6%, n=2) vs 71% (n=22) (partial response 29%, n=9) (p=0.62). Median PFS was 5 vs 8 mos (p=0.08), and median OS 9 vs 17 mos (p=0.03). In multivariate analyses of the entire pt cohort (n=62), su tx was independently associated with OS (HR 0.6, p=0.001). Conclusions: In prmRCC patient, the VEGFR inhibitor su may be associated with an improved outcome vs the mTOR inhibitor tem.

10538 Background: Imatinib (IM) revolutionized the outcome of patients with advanced GISTs; however, disease progression eventually occurs due to IM resistance or intolerance. Sunitinib (SU) is an ...

[Graphic][1] INTRODUCTION Recent large randomized controlled trials (RCTs) have shown non-vitamin K antagonist oral anticoagulants (NOACs) are at least as effective as vitamin K antagonists (VKAs) for prevention of stroke or systemic embolism in patients with non-valvular atrial fibrillation (AF) and are associated with similar or lower rates of bleeding. The results for bleeding seen in Phase 3 trials might not be applicable to real world practice. We performed a large population-based study to determine the incidence of bleeding in patients with AF beginning treatment with dabigatran, rivaroxaban or a VKA. METHODS From the computerized database of the 4.5 million member Israeli Clalit Health Services health care provider, consecutive patients initiating a VKA or NOAC for AF between January 1, 2011 and December 31, 2013 were studied. For prevention of embolism in AF, dabigatran had regulatory approval for 36 months and rivaroxaban for 24 months. Bleeding patients who required hospitalization were identified and key clinical and laboratory data were recorded. Because patients received different anticoagulants for different durations, time-to-event analyses were performed and bleeding incidences were calculated and reported as rates per 100 patient-years of treatment. Bleeding sites and all-cause mortality within 30 days were recorded and case fatality rates were calculated as the proportions of bleeding patients who died within 30 days. RESULTS (Table1) 18249 patients initiated anticoagulants for AF: 9564 received VKA, 4170 received dabigatran 110 mg bid , 1806 received dabigatran 150 mg bid and 2709 received rivaroxaban. The bleeding rates per 100 patient-years were 3.9 in VKA-treated patients, 2.8 in dabigatran 150 mg patients, 4.6 in dabigatran 110 mg patients and 4.3 in rivaroxaban patients. The intracranial hemorrhage (ICH) rates per 100 patient-years were 0.70 in VKA-treated patients, 0.37 in dabigatran 150 mg patients, 0.49 in dabigatran 110 mg patients and 0.27 in rivaroxaban patients. The gastrointestinal (GI) hemorrhage rates per 100 patient-years were 1.88 in VKA-treated patients, 1.85 in dabigatran 150 mg patients, 3.36 in dabigatran 110 mg patients and 2.39 in rivaroxaban patients. The case fatality rate for any bleed was 21%; for ICH 28.8%, and for GI bleeds it was 11.1%. Multivariate analysis revealed that increased age and increased serum creatinine were risk factors for bleeding in NOAC-treated patients. CONCLUSIONS The results of our population-based non-randomized study of AF patients are consistent with the RCTs in showing similar rates of overall bleeding, an increase in GI bleeding associated with dabigatran and a reduction in ICH seen with both dabigatran and rivaroxaban. | | VKA | Dabigatran 150 mg | Dabigatran 110 mg | Rivaroxaban | Overall | | --------------------------------------------- | ----------------- | ----------------- | ----------------- | ----------------- | -------------- | | Number of patients | 9564 | 1806 | 4170 | 2709 | 18249 | | Age in years) Median (Range) | 79 (27-99) | 78 (52-89) | 82 (55-95) | 82 (58-91) | 80 (27-99) | | Women % | 43.8 | 45.1 | 47 | 38.6 | 43.7 | | Serum creatinine mg/dL Median (Range) | 1.2 (0.3-11.6) | 1.0 (0.5-4.4) | 1.2 (0.4-4.1) | 1.3 (0.5-3.5) | 1.2 (0.3-11.6) | | CHADS2 score Median (Range) | 3 (0-6) | 3 (1-6) | 4 (1-6) | 4 (2-6) | 3 (0-6) | | Anti aggregant use (%) | 52 | 50 | 35 | 55 | 48 | | Bleeds per 100 patient years (N) | 3.9 (372) | 2.8 (50) | 4.6 (191) | 4.3 (116) | (729) | | Fatalities within 1 month of hemorrhage N | 44 | 8 | 15 | 3 | 70 | | Intracranial hemorrhage N | 67 | 4 | 16 | 3 | 90 | | Gastrointestinal hemorrhage N | 178 | 20 | 108 | 26 | 332 | Table 1: Clinical profile of patient cohort Disclosures Ellis: Boehringer Ingelheim: Honoraria. Eikelboom: Bayer: Honoraria, Research Funding; Bristol Meyers Squibb: Honoraria, Research Funding; Boehringer Ingelheim: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding. [1]: /embed/inline-graphic-2.gif

639 Background: L and T “beyond progression” (TBP) for MBC pts who progressed on 1st line therapy with T, are both reimbursed in Israel since 1/2010. The relative efficacy of L vs. T when combined with chemotherapy in 2nd line therapy for HER2+ MBC is unknown. In this retrospective database study we compared outcomes of 2ndline L or TBP, in the daily practice ("real life") in Israel. Methods: Using the computerized databases of Clalit Health Services' (CHS), Israel's largest health care provider, we identified all MBC pts that received 2nd line anti HER2 therapy, with either L or TBP after a 1stline protocol containing T, between 1/1/2010 and 31/12/2011. Pts characteristics and treatments were retrieved. The primary end point was overall survival (OS) defined as the time interval between date of initiation of 2nd line anti HER2 therapy and death or last day of follow-up. Secondary endpoint was progression free survival (PFS), defined as duration of 2nd line therapy. Results: The study population included 83 pts (28 L and 55 TBP). Mean age (59.9 vs. 61.4) and average Charlson co-morbidity index score (6.54 vs. 6.13) were similar between the cohorts. The groups differed in rates of prior adjuvant T (32.1% vs. 10.9%, p=0.017). The interim cutoff date for analysis was 31/12/2012 (allowing at least 12 months of follow-up). Median OS was 10.0 months for L pts (95% CI: 7.41–12.59) and was not reached for TBP, with a total of 31 deaths: 19 [67.9%] in the L group and 22 [40.0%] in the TBP group. A Cox regression showed an adjusted hazard ratio (HR) of 1.44 (95% CI 0.74-2.81), not significant (p=0.28).Prior adjuvant therapy with T was found to be a significant cofounder; HR=3.16 (95% CI 1.52-6.56). Median PFS was 6.0 months (95% CI: 4.31–7.69) for L and 7.0 months (95% CI: 4.30-9.70) for TBP, with a Cox regression adjusted HR of 0.87 (95% CI: 0.50-1.52), not statistically significant (p=0.87). Conclusions: In this retrospective database analysis, our interim results suggest no statistically significant difference in OS and PFS between L and TBP, as 2nd line therapy for HER2+ MBC, however the data showed a strong trend toward a survival benefit with TBP. A longer follow-up is required.

11513 Background: Six years after including Trastuzumab in the Israeli ‘National Health Basket‘ (NHB) for metastatic breast cancer (MBC), we evaluated its ‘real-life‘ use in terms of duration of treatment (DOT) and survival after initiation of treatment. Methods: The computerized database of Clalit Health Services’ (CHS), the largest Israeli sick fund, was used to determine DOT and survival (at Dec. 31, 2005), in all CHS patients with MBC that started Trastuzumab therapy during years 2000–2003. Results: * At Dec. 31, 2005. ** However, most received AC as adjuvant. Conclusions: A longitudinal analysis of Trastuzumab use shows a difference of 40–100% between the median and mean DOT. This difference is attributed to a sizeable proportion (∼15%) of patients that are “long-term responders” and are treated for more than 24 months. In these patients, we can assume that the HER-2 amplification is an essential transforming event. We recommend investigating the molecular characteristics of long-term responders. [Table: see text] No significant financial relationships to disclose.

e14571 Background: Bevacizumab is included in the Israeli National List of Reimbursed Drugs (NLRD) for 1st line treatment of all metastatic colorectal cancer (mCRC) patients since 7/2006. This study evaluates the "real life" impact of adding bevacizumab to 1st line treatment of mCRC by comparing patients' outcomes before and after the drug's availability in the NLRD. Methods: We conducted a retrospective database study ,using the computerized databases of Clalit Health Services' (CHS), Israel's largest health care provider, to compare two cohorts: (A) all CHS' patients diagnosed with mCRC between 1/2000-12/2004 that received 1st line irinotecan or oxaliplatin-based combination chemotherapy (before bevacizumab was introduced), and (B) all CHS's patients that started 1st line treatment with irinotecan or oxaliplatin-based combination chemotherapy and bevacizumab between 7/2006 and 8/2009 (allowing a minimum follow-up of 3 years). The primary endpoint was overall survival (OS) and the secondary endpoints were 1st line progression free survival (PFS) and metastatectomy rates. Since data on actual progression status was unavailable, PFS was defined as the duration of 1st line treatment. As CHS covers more than 50% of the Israeli population, our study may represent the general care received by Israeli patients with mCRC. Results: The study population included 1,739 patients: 1,052 in cohort A and 687 in cohort B. Patient demographics were similar between the cohorts. Median OS was 15.0 months for cohort A (95% CI: 13.4–16.6) and 23.0 months for cohort B (95% CI: 21.7–24.3), with an unadjusted hazard ratio (HR) of 0.71 (95% CI: 0.64-0.80, pst line treatment of mCRC were significantly higher in the later period of the study. The addition of bevacizumab to standard treatment of mCRC may have had a major contribution to this improvement.