This study tested the capability of an assay to predict aspirin response and reduce ischemic events, and healthcare costs, and delays to optimal treatment. Patients who needed aspirin in the course of normal medical care were included. Patients were excluded if they had disorders affecting platelet function, alcohol use within 24 hours of a test, or NSAID use. Dose escalation of chewable aspirin from 81 mg, to 162 mg, to 325 mg daily occurred based on the results of whole blood impedance aggregation testing to the agonists, collagen (1ug/mL, 5 ug/mL) and arachidonate (0.5 mM) after 10-14 days of treatment. The experimental in vitro test was conducted in triplicate by performing aggregometry on samples spiked to a concentration of 10 uM of aspirin in 0.05% dimethyl sulfoxide. Of the 36 patients who were compliant 16 were found to be resistant to the antiplatelet effects of 81 mg daily aspirin. Nine of these patients were predicted to stay resistant despite dose increase. Once tested at higher doses, ten remained resistant. Seven of the 16 patients were predicted to become sensitive to a higher dose while six actually did. Predicted response to increased doses of aspirin was in good agreement with actual response. Sensitivity of the assay was 83% and specificity was 80%. Results are promising and indicate that it is possible to predict, with reasonable accuracy, if a patient will have an adequate platelet response to aspirin or if the patient will never respond to aspirin necessitating an alternative antiplatelet regimen. Larger, multisite studies are inevitably needed.

Background: Low-density lipoproteins levels are significant predictors of clinical outcomes in ovarian cancer (OvCa) patients. Despite American Diabetes Association (ADA) guidelines, suboptimal hyperlipidemia management is reported in women diagnosed with both OvCa and diabetes mellitus (DM). This study evaluated the impact of cholesterol drugs utilization and importance of following ADA guidelines on OvCa recurrence and survival. Methods: All DM patients newly diagnosed with OvCa between 2003 and 2010 at Roswell Park Cancer Institute were retrospectively reviewed (n=482). A total of 60 newly diagnosed OvCa patients having a form of diabetes at the time of cancer diagnosis were identified. Out of these, 14 patients were excluded due to presence of type 1 diabetes (n=6) or prior cancer history (n=8). The remaining 46 patients were included in the final analyses. Tumor pathology, outcomes, baseline co-morbidities and self-reported drug therapy were documented. Follow-up began at cancer diagnosis and ended with first confirmed recurrence and/or death. Cases lost to follow-up were censored at the date of last contact. To analyze categorical outcomes across different treatment groups, Fisher's exact test was used. All multivariate analyses were done using Cox proportional hazards models while accounting for age, weight, stage, histology, and cumulative comorbidity. A nominal significance level of 0.05 was used in all testing. Results: Average age at diagnosis and body mass index in this data set was 70±10 years and 34.76±7.07 kg/m2, respectively. Over three quarters of this population was diagnosed with advanced stage OvCa and 96% had a tumor grade of 2 or higher. Roughly two thirds of the tumors evaluated had a serous histology. Out of the cases reviewed, 52% did not receive any form of cholesterol management and 46% received a statin alone or in combination. After a median follow-up of 26.9 months, patients receiving statin monotherapy for cholesterol management were found to have improved recurrence (HR=0.17, 95% CI: 0.04 to 0.73, P=0.02); however, no impact on overall mortality was noted as compared to patients not receiving any cholesterol management medication. Conclusions: This study explored for the first time the association between statin utilization and prognosis in OvCa patients with DM. Given the identified benefit, reinforcing compliance with DM guidelines for hyperlipidemia management in OvCa patients deserves further attention. Our findings seed the beginning of a novel approach in personalized OvCa care. Citation Format: Michelle E. Amsler, Kristina A. Chmiel, Olesya Yaremko, Clare Carroll, Jingjing Yin, Terry Mashtare, Anthony Miliotto, Rachel Brightwell, Kunle Odunsi, Alice C. Ceacareanu. Statins use prevents ovarian cancer recurrence in women with diabetes mellitus. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-18. doi:10.1158/1538-7445.AM2013-LB-18

Background: Association of non-secretagogues, metformin and thiazolidindiones, with lower cancer risk and improved survival has led to numerous clinical studies exploring their benefit as adjuvants in cancer chemotherapy. However, the most utilized, metformin, is contraindicated in patients undergoing radiologic studies involving intravenous administration of iodinated contrast media, such as patients with acute myeloid leukemia (AML). In these patients, metformin should be either withheld until renal function returns to normal or substituted with an alternate, in practice, often injectable insulin. Little is known about the consequences of metformin's substitution in patients whose cancer care requires periodic exposures to contrast dye or in which its reinitiation appears unsafe. Objective: This study compares the utilization of insulin and non-secretagogues, metformin and thiazolidindiones, in patients with diabetes mellitus newly diagnosed with AML or solid tumors. Methods: All diabetes mellitus (DM) patients diagnosed with AML (n1=65), breast (n2=290), ovarian (n3=46), prostate (n4=105) and kidney cancer (n5=95) between January 2003 and December 2010 at Roswell Park Cancer Institute in Buffalo, NY were included in the study (n=601). Patient demographics, tumor pathology, outcomes, baseline co-morbidities and self-reported drug therapy were documented. Follow-up began at cancer diagnosis and ended with first confirmed recurrence and/or death. Cases lost to follow-up were censored at the date of last contact. Kaplan-Meyer with log-rank statistics and Cox proportional hazards models were used for all multivariate analyses. A nominal significance level of 0.05 was used in all testing. Results: The median age was 62 years old in the solid tumor group and 69.5 years old in the AML group. Baseline utilization of non-secretagogues in DM patients diagnosed with solid tumors was associated with significantly improved overall mortality, as compared to baseline insulin utilization (X2=4.071, P=0.044). No baseline glucose lowering drug class utilization advantage was observed in the AML group. A stratified analysis of solid tumors and AML groups according to the respective drug utilization revealed a statistically significant difference in mortality in the favor of non-secretagogue utilization in DM patients with solid tumors, but not with AML (X2=258.36, p<0.001). Conclusion: We confirm a survival benefit for the patients receiving non-secretagogues as compared to insulin in the solid tumors group. The absence of non-secretagogue protection in the AML group could be potentially attributed to the substitution of metformin with injectable insulin at the time of AML diagnosis. Citation Format: Zachary A. P. Wintrob, Huan-Ching Chuang, Dustyn S. Miller, Jonathan L. Rabey, Thang Q. Bui, Michelle E. Amsler, Laurie-Ann Ford, Meir Wetzler, Alice C. Ceacareanu. Missing the benefit of metformin in AML: A problem of contrast. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-17. doi:10.1158/1538-7445.AM2013-LB-17

e18813 Background: Use of biosimilars is an effective strategy in expanding access to care and lowering healthcare costs. Literature about the successes, challenges, and best practices of biosimilar adoption in oncology is limited. We aim to describe the current state of biosimilars in oncology practices and barriers to adoption. Methods: A 40-question survey was developed to gather information regarding biosimilar use in the following areas: formulary management, product usage, policies, technology, safety, and education. The following biosimilars were evaluated: bevacizumab (B), filgrastim (F), epoetin (E), infliximab (I), pegfilgrastim (P), rituximab (R), and trastuzumab (T). The survey was distributed to Hematology/Oncology Pharmacy Association members. Results: A total of 179 surveys were initiated, with a completion rate of 31%. Six surveys were removed due to duplication, resulting in 50 unique surveys with 21 responses (42%) from NCI-designated comprehensive cancer centers. Inpatient formulary decisions were driven by acquisition cost followed by reimbursement. In the outpatient setting, equal consideration was given to acquisition cost and reimbursement for formulary decisions. Thirty-two percent of institutions restricted biosimilars to their FDA approved indication. Sixty-six percent of institutions had a biosimilar interchangeability policy in place. For the corresponding reference products, overall average utilization of biosimilars was B 74%, F 88%, E 82%, I 57%, P 52%, R 73%, and T 71%. More than 90% of institutions had a preferred biosimilar on formulary. Based on the results, 72% stated payors specified the selection of biosimilars, and 76% stated payor reimbursement limited ability to participate in contract pricing. Insurance reimbursement was recognized as the main barrier to adoption (Table). Medication errors related to biosimilar use were reported by 26% respondents, with the most common cause listed as communication. Thirty-six percent of institutions provided education on the general use of biosimilars and 38% had biosimilar products in treatment specific education. Conclusions: Biosimilar adoption is consistent across responding institutions, with noted utilization shift towards biosimilar products compared to reference. Decisions for biosimilar adoption are made based on cost and reimbursement. Opportunities exist in the collaboration of health systems and payors to align formularies and promote safe and cost-effective care for their members.[Table: see text]

20%-40% of patients being treated with aspirin for secondary prophylaxis of stroke or myocardial infarction may derive no antiplatelet effects. Early identification of patients as pharmacokinetically or pharmacodynamically resistant to aspirin has the potential to become an invaluable clinical tool, reducing delays to optimal treatment, cardiovascular events, and healthcare costs. This study tested the capability of an assay that was previously developed in healthy volunteers, to differentiate between these two types of resistance in patients. Patients who needed aspirin treatment in the course of normal medical care were included. Dose escalation of chewable aspirin from 81 mg, to 162 mg, to a maximum 325 mg daily occurred every 10-14 days based on the results of whole blood impedance aggregation testing to the agonists, collagen (1 ug/mL, 5 ug/mL) and arachidonate (0.5 mM). The in vitro test was conducted in triplicate by performing the same aggregometry test on blood samples spiked to a concentration of 10 uM of aspirin in 0.05% dimethyl sulfoxide. Resistance was defined as a response to collagen 1 ug/mL >10 ohms, and/or response to arachidonate >6 ohms, and/or the ratio of collagen 1 to 5 ug/mL >0.5. Patients were excluded if they had any disorders affecting platelet function, an abnormal CBC, alcohol use within 24 hours of a test, NSAID use, or had any conditions that would affect absorption. Of the 36 patients included who were compliant with their 81 mg aspirin regimen based on pill count, 16 were found to be resistant to 81 mg of aspirin. Nine of these patients were predicted to stay resistant despite dose increase. Once tested at higher doses, ten actually remained resistant. Seven of the 16 patients were predicted to become sensitive to a higher dose of aspirin while six actually did. No statistical difference was found between predicted aspirin response and actual aspirin response (p=0.61). Sensitivity was 83% and specificity was 80%. In conclusion, results are promising and indicate that it is possible to predict, with reasonable accuracy, if a patient will have an adequate platelet response to aspirin or if the patient will never respond to aspirin therapy necessitating an alternative antiplatelet regimen. Larger, multi-site studies are inevitably needed.