Real-World Noninferiority Assessment of Two Filgrastim Biosimilars in Patients Receiving Myelosuppressive Chemotherapy.

PURPOSE: Although multiple filgrastim biosimilars are now available in the United States, no studies comparing clinical outcomes between products have been reported. This analysis evaluated real-world outcomes of filgrastim-aafi and filgrastim-sndz in patients with select solid tumors receiving myelosuppressive chemotherapy to compare the two filgrastim biosimilars. METHODS: This was an observational, noninferiority, cohort study of patients from three integrated health care systems who received myelosuppressive chemotherapy and were prophylactically initiated on filgrastim-sndz between January and November 2021 or filgrastim-aafi between June and November 2022. Patients were followed from filgrastim biosimilar initiation until the start of their next chemotherapy cycle. The primary outcome of severe neutropenia was analyzed using a binary noninferiority test with a 5% upper margin. Secondary outcomes included the incidence of emergency department or hospital encounters due to febrile neutropenia and systemic antibiotic/antifungal medication use. If noninferiority was met, adjusted logistic regression modeling was conducted. RESULTS: A total of 2,730 patients who initiated filgrastim-aafi (n = 880) or filgrastim-sndz (n = 1,850) during the study period were included. The overall mean age was 55 years, 87.4% were female, 42.3% were White, and 76.6% had breast cancer. Severe neutropenia occurred in 1.8% and 1.7% of patients initiated on filgrastim-aafi and filgrastim-sndz, respectively (P < .01 for noninferiority). The adjusted odds ratio for severe neutropenia with filgrastim-aafi compared with filgrastim-sndz was 0.91 (95% CI, 0.49 to 1.68; P = .76). Noninferiority was met for all secondary outcomes (P < .01), and there were no adjusted statistically significant differences between the groups (all P > .05). CONCLUSION: Among patients with select solid tumors receiving myelosuppressive chemotherapy, severe neutropenia outcomes were comparable between filgrastim-aafi and filgrastim-sndz biosimilars. Findings from this study may support utilization of different filgrastim biosimilars in clinical practice.

Real-World Clinical Outcomes of Bevacizumab-awwb Biosimilar versus Bevacizumab Reference Product in Patients with Metastatic Colorectal Cancer.

BACKGROUND: Bevacizumab-awwb was the first biosimilar approved for cancer treatment in the USA. Limited information is available on the real-world comparative safety and effectiveness of bevacizumab biosimilars, especially for indications granted approval through extrapolation. OBJECTIVE: To evaluate the real-world outcomes of patients with metastatic colorectal cancer (mCRC) initiated on bevacizumab-awwb versus bevacizumab reference product. PATIENTS AND METHODS: This was an observational, longitudinal cohort study of US adult patients with mCRC from four integrated care delivery systems who were newly initiated on bevacizumab-awwb between 1 July 2019 and 30 March 2020 or bevacizumab reference product between 1 July 2015 and 30 June 2018. Patients were followed until 1 year after treatment initiation, end of plan membership, or death, whichever occurred first. The primary outcome of overall survival (OS) was analyzed using a binary non-inferiority test with lower margin of 10% and adjusted Cox proportional hazards regression analysis to assess all-cause mortality if non-inferiority was met. Secondary outcomes included counts of doses received, treatment duration, all-cause hospitalizations, and incidence of serious adverse events. RESULTS: A total of 1445 patients initiated on either bevacizumab-awwb (n = 239) or bevacizumab reference product (n = 1206) were included in the analysis. The mean overall age was 60 ± 13 years, 46% of patients were female, and 51% were white. The OS rate was 72.8% and 73.1% for patients receiving bevacizumab-awwb and bevacizumab reference product, respectively (p < 0.01 for non-inferiority). The adjusted hazard ratio for mortality was 1.01 (0.77-1.33, p = 0.93). There were no statistically significant differences in secondary outcomes between the study groups. CONCLUSIONS: These findings suggest that bevacizumab-awwb is as effective and safe as bevacizumab reference product for the real-world treatment of mCRC.

Transthyretin Amyloid Cardiomyopathy Risk Evaluation in a Cohort of Patients With Heart Failure.

Introduction Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, infiltrative form of heart failure (HF). Nevertheless, ATTR-CM is a largely underrecognized and misdiagnosed condition. This study's objective was to develop an efficient model to assess the chance of ATTR-CM in patients with HF. Methods This was an observational study of patients with HF who had a confirmed diagnosis of ATTR-CM and those with HF but without known ATTR-CM between January 1, 2019, and July 1, 2021. Patient characteristics were extracted from administrative and claims electronic databases and compared between the groups. A propensity score for having ATTR-CM was modeled. Samples of 50 control patients with the highest and lowest propensity scores were adjudicated to assess whether further workup to evaluate for ATTR-CM was warranted for each patient. The sensitivity and specificity of the model were calculated. Results Thirty-one patients with confirmed ATTR-CM and 7620 patients without known ATTR-CM were included in the study. Patients with ATTR-CM were more likely to be Black and to have atrial flutter/fibrillation, cardiomegaly, HF with preserved ejection fraction, pericardial effusion, carpal tunnel syndrome, joint disorders, and lumbar spinal stenosis and to use a diuretic (all p < 0.05). A propensity model with 16 inputs was developed (c-statistic = 0.875). The model's sensitivity and specificity were 71.9% and 95.2%, respectively. Conclusion The propensity model developed in this study provided an efficient means for identifying patients with HF who are more likely to have ATTR-CM and may warrant further workup.

Impact of Palliative Care Clinical Pharmacists in an Inpatient Care Setting on Total Health Care Expenditures.

Background: Inpatient palliative care clinical pharmacy specialists (IPCPS) on multidisciplinary palliative care (PC) teams have expanding roles in the treatment of pain, nausea, and other symptoms for patients with serious illnesses. Objectives: The aim of this study was to assess the clinical and financial outcomes associated with an IPCPS on an inpatient PC team. Setting and Design: This was a retrospective cohort study conducted in Colorado. Adult patients with an inpatient stay and a PC consult between October 1, 2016 and February 28, 2019 were included. Patients were assigned to the observation group if they received PC from a clinical pharmacist and control group if they received usual PC. The primary outcome was the 180-day change in daily total cost-of-care expenditures. Secondary outcomes included length of index hospitalization and 180-day change in daily morphine milligram equivalents (MME), health care utilization, and opioid adverse effects (AE). Results: A total of 1543 patients were included with 228 and 1315 in the IPCPS and usual care groups, respectively. After adjustment, the IPCPS group had a greater median decrease in daily expenditures (-$22 vs. $6, p = 0.003), higher median increase in daily MME (16.5 vs. 9.7 mg, p = 0.007), and fewer patients with a subsequent hospitalization (34.2% vs. 39.2%, p = 0.010) or urgent care visit (10.5% vs. 14.6%, p = 0.024) but longer mean index hospitalization (9.3 vs. 7.7 days, p = 0.003) and no differences in AE during follow-up (all p > 0.05). Conclusion: IPCPS participation on the PC team can be a component of health care cost reduction while contributing to patient-centered quality care.

Clinical Effectiveness of an Outpatient Multidisciplinary Chronic Pain Management Telementoring Service.

OBJECTIVE: The objective of this study was to assess the effectiveness of a Pain E-Consult Program (PEP), a multidisciplinary telementoring service based on the Extension for Community Healthcare Outcomes (ECHO) model to reduce opioid use in the outpatient setting. MATERIALS AND METHODS: This was a retrospective matched cohort study conducted in an integrated health care delivery system. Adult patients without cancer and with a 90-day morphine milligram equivalent (MME) ≥30 mg/d between April 1, 2016, and June 30, 2017, were included. Patients whose primary care clinician received the PEP (observation) were compared with usual care (control) patients. Observation patients were matched up to 1:5 to control patients. Outcomes included change in MME and initiation of nonopioid alternative medications. Multivariable regression analyses were performed. RESULTS: A total of 665 patients were matched: 125 and 540 in the observation and control groups, respectively. Patients were primarily female, white, and Medicare beneficiaries. The observation group had a statistically significantly greater decrease in median MME/day during the 6-month (-7.4 vs. 1.5 mg, P=0.002) and 12-month (-15.1 vs. -2.8 mg, P<0.001) follow-up and rates of ≥20% decrease (6 mo: 41.6% vs. 24.6%, P=0.003; 12 mo: 48.0% vs. 32.6%, P=0.017). There were no differences in the rates of initiation of nonopioid alternative medications. CONCLUSIONS: A PEP was associated with greater reductions in MME/day compared with usual care despite similar rates of nonopioid alternative medication initiation. A prospective randomized study of this program should be undertaken to confirm these findings.

Retrospective Cohort Study Comparing Infliximab-dyyb and Infliximab in Biologic-Naive Patients With Inflammatory Bowel Disease in the United States.

Background: Real-world assessments of biosimilars are needed to understand their effectiveness and safety in practice settings that may differ from those seen in clinical trials or healthcare systems in different countries. To assess the effectiveness and safety of a biosimilar (infliximab-dyyb) and its reference product (infliximab) in patients with inflammatory bowel disease (IBD) in the United States. Methods: We conducted a retrospective cohort study of biologic-naive patients with IBD who started treatment with infliximab-dyyb or infliximab. The study included 3206 patients identified through electronic health records in a US integrated healthcare delivery system. The effectiveness outcome was a composite of IBD-related surgery, IBD-related emergency room visit, and IBD-related hospitalization within 12 months of initiation. Safety outcomes included incidence of any or serious infection, cancer, acute liver dysfunction, and tuberculosis. We used a non-inferiority test with an upper-limit margin of 10% to analyze effectiveness. Doubly robust methods incorporating Cox proportional hazard regression with standardized inverse probability of treatment weighting were used to analyze both effectiveness and safety outcomes. Results: The composite effectiveness outcome occurred in 107 of 870 patients (12.3%) in the infliximab-dyyb and 379 of 2336 patients (16.2%) in the infliximab groups. Infliximab-dyyb was non-inferior (P < .01) and was not different (hazard ratio [HR] 0.81; confidence interval [CI] 0.65-1.01; P = .06) to infliximab. Safety outcomes were not different between infliximab-dyyb and infliximab for any infections (HR 1.01; CI 0.86-1.17; P = .95), serious infections (HR 0.83; CI 0.54-1.26; P = .38), cancers (HR 0.83; CI 0.44-1.54; P = .55), and tuberculosis (HR 0.59; CI 0.10-3.55; P = .57). Conclusions: Initiation of infliximab-dyyb was non-inferior to infliximab among biologic-naive patients with IBD in an US integrated healthcare delivery system.

Temporal trends in first-line outpatient anticoagulation treatment for cancer-associated venous thromboembolism.

BACKGROUND: First-line treatment and secondary prevention of venous thromboembolism (VTE) in patients with cancer consisted, historically, of unfractionated heparin or low-molecular weight heparin (LMWH). With recent clinical trials of direct oral anticoagulants (DOAC) showing similar efficacy as LMWH, little is known about anticoagulant prescribing patterns in patients with cancer and a VTE. This study characterized the temporal trends in first-line outpatient anticoagulation therapy for cancer-associated VTE. MATERIALS AND METHODS: This retrospective cohort study of patients who were hospitalized for a cancer-associated venous thromboembolism (VTE) between 01/01/2000 and 10/31/2017 identified patients from the cancer registries at two regions of an integrated healthcare delivery system. The primary outcome was the trend in age- and sex-adjusted rates of first-line anticoagulant therapy during the 30 days post-hospital discharge. Therapies were categorized as 1) injectable LMWH monotherapy, 2) warfarin ± injectable, 3) injectable fondaparinux monotherapy, or 4) DOAC ± injectable. RESULTS: Overall, 9816 patients were included with a mean age of 66 ± 13 years and 54% were female. From 2000 to 2003, warfarin ± injectable was used in ≈90% of cases. After 2003, there was a steady decline in warfarin use (25% in 2017) corresponding with increased LMWH use: 11% in 2003 to 55% in 2017. The DOAC ± injectable use has rapidly increased from <1% in 2014 to 20% in 2017. CONCLUSIONS: From 2000 to 2017, first-line anticoagulant therapy for cancer-associated VTE has experienced a substantial increase in LMWH and DOAC use with a resultant decline in warfarin use.

Indications for Rituximab Use in an Integrated Health Care Delivery System.

BACKGROUND: Rituximab is a top-selling biologic that was first approved by the FDA in 1997 for a non-Hodgkin lymphoma orphan indication. It has since been approved for additional orphan indications, with rheumatoid arthritis as the only FDA-approved, nonorphan indication. Evidence suggests that rituximab is frequently used off-label, but information on its use over time and indications for use in the United States is limited. OBJECTIVE: To assess incident rituximab use over time in an integrated health care delivery system. METHODS: This was a cross-sectional, retrospective study. Data were collected from administrative databases and manual chart reviews. Patients who received their first rituximab infusion between October 1, 2009, and December 31, 2017, and who were not a part of a clinical trial were included. Indication for use (FDA-approved orphan/nonorphan, off-label) was determined. Proportions of use were assessed over time. Multivariable logistic regression modeling was performed to assess factors associated with receiving rituximab for an FDA-approved indication. RESULTS: A total of 1,674 patients were included. The majority (66.4%) of patients had an FDA-approved indication, with lymphoma being the most common approved indication (66.4%). The most common indication for off-label use was neurologic conditions (72.7%), predominantly demyelinating diseases. Off-label indication use increased from 1.2% in 2009 to 55.6% in 2017. Factors associated with rituximab use for an FDA-approved indication included increased age (adjusted odds ratio [AOR] = 1.05, 95% CI = 1.04-1.07) and increased burden of chronic disease (chronic disease score: AOR = 1.07, 95% CI = 1.02-1.12; Charlson Comorbidity Index score: AOR = 3.52, 95% CI = 3.03-4.10). CONCLUSIONS: Off-label use of rituximab grew dramatically over the course of the study. With the recent FDA approval of the rituximab biosimilar and its expected lower price, off-label use will likely continue to rise. Opportunities for cost savings and to ensure appropriate use of these medications should be evaluated. DISCLOSURES: This study was funded by Kaiser Permanente. All authors except Hansen are employed by Kaiser Permanente. Hansen has nothing to disclose. Preliminary results were presented at the Mountain States Conference for Residents and Preceptors in May 2019 in Salt Lake City, UT, and at an encore presentation October 2019 at the American College of Clinical Pharmacy Annual Meeting in New York, NY.

Guideline-recommended incorporation of biomarker testing results in metastatic colorectal cancer therapy.

Aim: To describe pharmacogenomic tumor testing among patients with metastatic colorectal cancer. Methods: This was a retrospective study of patients with metastatic colorectal cancer diagnosed between 1 January 2014 and 30 June 2018. Patients were assessed for pharmacogenomic testing and appropriateness of chemotherapy use. Results: Overall, 112/167 (67.1%) patients had at least one of the three recommended pharmacogenomic tests and 41/167 (24.6%) had all tests. Twenty-four patients were treated with cetuximab with 8/167 (4.7%) identified as being treated with a RAS variant (n = 3) or incomplete testing (n = 5); thus, not in accordance with guidelines. Conclusion: Uptake of testing was variable but increased over time; however, a small proportion of patients received cetuximab with a variant or not all recommended tests being performed.

Universal hepatitis B screening and management in patients with cancer who received immunosuppressive chemotherapy.

BACKGROUND: Clinical data to guide management of patients with cancer and hepatitis B virus (HBV) infection who are treated with immunosuppressive chemotherapy are lacking. The purpose of this study was to describe HBV+ rates in a population of patients with cancer and evaluate a risk-stratified management protocol for the prevention of HBV reactivation (HBVr). METHODS: This was a descriptive study conducted in an integrated healthcare delivery system. Patients with cancer and hepatitis B virus infection who received immunosuppressive chemotherapy between 1 January 2014 and 31 January 2016 were included. A risk-stratified management protocol that continued for six months after chemotherapy completion or 12 months after completion of B-cell targeted chemotherapy was assessed. Outcomes included the proportion of patients who were HBV+ and amongst patients who initiated immunosuppressive therapy, proportions who received hepatitis B virus monitoring or anti-hepatitis B virus prophylaxis, or experienced HBVr or hepatitis B virus-related complications. RESULTS: There were 2463 patients with cancer screened for hepatitis B virus with 114 (4.6%) HBV+ of whom 59 (51.8%) initiated chemotherapy. Included patients were primarily older, male, and white with gastrointestinal or hematologic cancers and initiated intermediate/low-risk cytotoxic chemotherapy. During follow-up, 41 (69.5%) received hepatitis B virus DNA monitoring and 17 (28.8%) initiated anti-hepatitis B virus prophylaxis. No HBVr was observed. ALT and AST abnormalities were common but mostly Grade 1 and primarily related to the patient's malignancy or medications. CONCLUSIONS: Universal hepatitis B virus screening coupled with a risk-stratified management strategy utilizing HBVr monitoring and anti-hepatitis B virus prophylaxis in HBV+ patients receiving immunosuppressive chemotherapy for cancer may prevent HBVr.

Bridge Therapy Outcomes in Patients With Mechanical Heart Valves.

BACKGROUND: Bridge therapy is associated with an increased risk of major bleeding in patients with atrial fibrillation and venous thromboembolism (TE) without a corresponding reduction in TE. The benefits of bridge therapy in patients with mechanical heart valve (MHV) prostheses interrupting warfarin for invasive procedures are not well described. METHODS AND RESULTS: A retrospective cohort study was conducted at an integrated health-care delivery system. Anticoagulated patients with MHV interrupting warfarin for invasive diagnostic or surgical procedures between January 1, 2006, and March 31, 2012, were identified. Patients were categorized according to exposure to bridge therapy during the periprocedural period and TE risk (low, medium, and high). Outcomes validated via manual chart review included clinically relevant bleeding, TE, and all-cause mortality in the 30 days following the procedure. There were 547 procedures in 355 patients meeting inclusion criteria. Mean cohort age was 65.2 years, and 38% were female. Bridge therapy was utilized in 466 (85.2%) procedures (95.2%, 77.3%, and 65.8% of high, medium, and low TE risk category procedures, respectively). The 30-day rate of clinically relevant bleeding was numerically higher in bridged (5.8%; 95% confidence interval [CI], 3.9%-8.3%) versus not bridged procedures (1.2%; 95% CI, <0.1%-6.7%; P = .102). No TEs or deaths were identified. CONCLUSION: The use of bridge therapy is common among patients with MHV and may be associated with increased bleeding risk. Further research is needed to determine whether bridge therapy reduces TE in patients with MHV interrupting warfarin for invasive procedures.

Effect of Angiotensin System Inhibitors on Survival in Patients Receiving Chemotherapy for Advanced Non-Small-Cell Lung Cancer.

INTRODUCTION: Preclinical studies suggest that angiotensin system inhibitors (ASI) and bevacizumab improve tumor perfusion and chemotherapy efficacy. We performed a retrospective study to examine whether concomitant ASI use during carboplatin and paclitaxel (CP) without or with bevacizumab (CPB) was associated with improved overall survival (OS) in patients with advanced nonsquamous, non-small-cell lung cancer (NS-NSCLC). PATIENTS AND METHODS: In a retrospective cohort study, adult patients diagnosed with stage IIIB or IV NS-NSCLC between 2005 and 2011 were identified from tumor registries at 1 of 4 Kaiser Permanente regions. Survival differences between those who did and did not receive ASIs concomitant with chemotherapy (CP or CPB) were assessed using propensity score-matched proportional hazard models. OS was measured from the initiation of chemotherapy until death, disenrollment, or December 31, 2012. RESULTS: Of the 1465 CP and 348 CPB patients included, 273 (19%) and 78 (22%), respectively, received concomitant ASI. For CP patients with and without concomitant ASI exposure, median OS was 12.0 and 8.4 months, respectively (crude hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.63-0.84). For CPB patients, the comparable median OS was 14.9 and 11.9 months, respectively (crude HR, 0.77; 95% CI, 0.57-1.02). Using propensity score-matched cohorts, the HR for concomitant ASI use was 0.73 (95% CI, 0.61-0.88) for CP patients and 0.79 (95% CI, 0.51-1.21) for CPB patients. CONCLUSION: Concomitant ASI receipt during CP or CPB therapy for NS-NSCLC was associated with improved survival, although the association was only statistically significant in the CP group.

Use of Bevacizumab in Community Settings: Toxicity Profile and Risk of Hospitalization in Patients With Advanced Non-Small-Cell Lung Cancer.

PURPOSE: Little is known regarding toxicities and hospitalizations in community-based settings for patients with advanced non-small-cell lung cancer (NSCLC) who received commonly prescribed carboplatin-paclitaxel (CP) or carboplatin-paclitaxel-bevacizumab (CPB) chemotherapy. METHODS: Patients with stages IIIB-IV NSCLC age ≥ 21 years diagnosed between 2005 and 2010 who received first-line CP or CPB were identified at four health maintenance organizations (N = 1,109). Using patient and tumor characteristics and hospital and ambulatory encounters from automated data in the 180 days after chemotherapy initiation, the association between CP and CPB and toxicities and hospitalizations were evaluated with χ(2) tests and propensity score-adjusted regression models. RESULTS: Patients who received CPB were significantly younger and had significantly more bleeding, proteinuria, and GI perforation events (all P < .05). For these patients, the unadjusted odds ratio associated with the likelihood of having a hospitalization was 0.46 (95% CI, 0.32 to 0.67). As shown by multivariable and propensity score-adjusted models, patients who received CPB were less likely to have been hospitalized (odds ratio, 0.48; 95% CI, 0.32 to 0.71) and had fewer total hospitalizations (rate ratio, 0.62; 95% CI, 0.47 to 0.82) and hospital days (rate ratio, 0.53; 95% CI, 0.47 to 0.60) than patients who received CP. CONCLUSION: Consistent with earlier randomized clinical trials, significantly more toxicity events were identified in patients treated with CPB. However, both unadjusted and adjusted models showed that patients who received CPB were less likely than patients who received CP to experience a hospital-related event after the initiation of chemotherapy. Findings here confirm the need for adherence to clinical recommendations for judicious use of CPB, but provide reassurance regarding the relative risk for hospitalizations.

Bleeding, Recurrent Venous Thromboembolism, and Mortality Risks During Warfarin Interruption for Invasive Procedures.

IMPORTANCE: The risk of bleeding and recurrent venous thromboembolism (VTE) among patients receiving long-term warfarin sodium therapy for secondary VTE prevention who require temporary interruption of anticoagulant therapy for surgery or invasive diagnostic procedures has not been adequately described. OBJECTIVE: To describe the rates of clinically relevant bleeding and recurrent VTE among patients in whom warfarin therapy is interrupted for invasive procedures and compare these rates among patients who did and did not receive bridge therapy. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted at Kaiser Permanente Colorado, an integrated health care delivery system. Patients in whom warfarin therapy was interrupted for invasive diagnostic or surgical procedures between January 1, 2006, and March 31, 2012, were identified via queries of administrative data sets. A total of 1812 procedures in 1178 patients met inclusion criteria. Data on outcomes and exposures were collected between June 1, 2005, and April 30, 2012. EXPOSURES: Use of bridge therapy vs no bridge therapy during warfarin interruption. MAIN OUTCOMES AND MEASURES: Thirty-day clinically relevant bleeding, recurrent VTE, and all-cause mortality. Outcomes were verified via manual review of medical records. RESULTS: Among the 1178 patients, the mean (SD) age was 66.1 (12.7) years, 830 procedures (45.8%) were in men, and the most common indication for warfarin therapy was deep vein thrombosis (56.3%). Most patients were considered to be at low risk for VTE recurrence at the time of warfarin interruption (1431 procedures [79.0%]) according to the consensus guidelines of the American College of Chest Physicians. Clinically relevant bleeding within 30 days after the procedure in the bridge therapy and non-bridge therapy groups occurred in 15 patients (2.7%) and 2 patients (0.2%), respectively (hazard ratio, 17.2; 95% CI, 3.9-75.1). There was no significant difference in the rate of recurrent VTE between the bridge and non-bridge therapy groups (0 vs 3; P = .56). No deaths occurred in either group. CONCLUSIONS AND RELEVANCE: Bridge therapy was associated with an increased risk of bleeding during warfarin therapy interruption for invasive procedures in patients receiving treatment for a history of VTE and is likely unnecessary for most of these patients. Further research is needed to identify patient- and procedure-related characteristics associated with a high risk of perioperative VTE recurrence during warfarin therapy interruption.

Cluster-Randomized Trial of Clinical Pharmacist Tobacco Cessation Counseling Among Patients with Cardiovascular Disease.

Optimal management of patients with cardiovascular disease (CVD) includes evaluation of risk factors using a team-based approach. Tobacco use often receives less attention than other CVD risk factors; therefore, utilization of nonphysician health care providers may be valuable in addressing tobacco use. The purpose of this trial was to assess the impact of brief, structured, telephone tobacco cessation counseling (BST) delivered by clinical pharmacists on tobacco cessation attempts compared to usual care. The BST consisted of 1 to 5 minutes discussing 3 key counseling points, including a recommendation to quit and education about cessation aids. This was a cluster-randomized trial of tobacco-using patients with CVD who were enrolled in a clinical pharmacist-managed, physician-directed, CVD disease state management service. Clinical pharmacists were randomized to provide usual care (control) or BST (intervention) to their tobacco-using patients during a 4-month period. Patients were surveyed 3 months later to assess their tobacco cessation attempts, use of tobacco cessation aids, and self-reported cessation. One hundred twenty patients were enrolled. Subjects were predominately white males, aged ≥65 years, with a history of myocardial infarction. One hundred and four subjects completed the follow-up survey. No differences were detected between the 36.2% and 38.6% of control and intervention subjects, respectively, reporting a tobacco cessation attempt (P=0.804) or in the other outcomes (all P>0.05). A BST delivered by clinical pharmacists may not adequately affect patient motivation enough to increase tobacco cessation attempts in tobacco-dependent patients with CVD. Future research is needed to evaluate other team-based strategies that can decrease tobacco use in patients with CVD.

Thromboembolic and bleeding outcomes of extended duration low-intensity warfarin following elective total knee arthroplasty.

INTRODUCTION: The purpose of this study was to describe the incidence of symptomatic venous thromboembolism (VTE), clinically-relevant bleeding, and death among a real-world population receiving warfarin prophylaxis targeting an international normalized ratio (INR) of 1.5 to 2.5 for four weeks following total knee arthroplasty (TKA). MATERIALS AND METHODS: This retrospective, observational study included patients receiving warfarin following a TKA between August 1, 2005 and July 31, 2009 identified in the Kaiser Permanente Total Joint Replacement Registry. Patients<18 years, receiving warfarin for another indication, or without continuous KPCO membership during the study period were excluded. RESULTS: There were 1487 patients with TKA included in the analysis. Mean patient age was 67.7 years and 61.7% were female. The median percent of time in therapeutic INR range during follow-up was 55% (interquartile range=35%-75%). Nineteen cases of symptomatic VTE [1.3%; 95% confidence interval (CI) 0.8%-2.0%] including ten pulmonary emboli (PE) (0.7%) were identified within 90 days of surgery. Clinically-relevant bleeding occurred in 1.7% (95% CI 1.1%-2.5%) of patients during warfarin prophylaxis and there were no deaths within 90 days of surgery. CONCLUSIONS: The rates of symptomatic VTE and clinically-relevant bleeding following TKA in patients receiving warfarin prophylaxis with a target INR of 1.5 to 2.5 were low. Additional studies should include low-intensity warfarin to identify the regimen that optimally balances risks of bleeding and symptomatic VTE after major orthopedic surgery.

Does KRAS testing in metastatic colorectal cancer impact overall survival? A comparative effectiveness study in a population-based sample.

PURPOSE: Epidermal growth factor receptor (EGFR) inhibitors are approved for treating metastatic colorectal cancer (CRC); KRAS mutation testing is recommended prior to treatment. We conducted a non-inferiority analysis to examine whether KRAS testing has impacted survival in CRC patients. PATIENTS AND METHODS: We included 1186 metastatic CRC cases from seven health plans. A cutpoint of July, 2008, was used to define two KRAS testing time period groups: "pre-testing" (n = 760 cases) and "post-testing" (n = 426 cases). Overall survival (OS) was estimated, and the difference in median OS between the groups was calculated. The lower bound of the one-sided 95% confidence interval (CI) for the difference in survival was used to test the null hypothesis of post-testing inferiority. Multivariable Cox regression models were constructed to adjust for covariates. RESULTS: The median unadjusted OS was 15.4 months (95% CI: 14.0-17.5) and 12.8 months (95% CI: 10.0-15.2) in the pre- and post-testing groups, respectively. The OS difference was -2.6 months with one-sided 95% lower confidence bound of -5.13 months, which was less than the non-inferiority margin (-5.0 months, unadjusted p = 0.06), leading to a failure to reject inferiority of OS in the post-testing period. In contrast, in the adjusted analysis, OS non-inferiority was identified in the post-testing period (p = 0.001). Sensitivity analyses using cutpoints before and after July, 2008, also met the criteria for non-inferiority. CONCLUSION: Implementation of KRAS testing did not influence CRC OS. Our data support the use of KRAS testing to guide administration of EGFR inhibitors for treatment of metastatic CRC without diminished OS.

Diffusion of Intraperitoneal Chemotherapy in Women with Advanced Ovarian Cancer in Community Settings 2003-2008: The Effect of the NCI Clinical Recommendation.

PURPOSE: A 2006 National Cancer Institute clinical announcement recommended the use of combined intravenous (IV) and intraperitoneal (IP) chemotherapy over IV chemotherapy alone for women with International Federation of Gynecology and Obstetrics (FIGO) stage 3 optimally debulked ovarian cancer due to significant survival benefit demonstrated in multiple randomized clinical trials. We examined uptake of IP chemotherapy in community practice before and after this recommendation. METHODS: We identified 288 women with FIGO stage 2 or greater incident ovarian cancer diagnosed from 2003 to 2008 at three integrated delivery systems in the US. Administrative health plan data were used to determine patient characteristics and receipt of IV and IP chemotherapy within 12 months of diagnosis. We compared characteristics of women receiving IV chemotherapy alone vs. IP chemotherapy (with or without IV chemotherapy) and assessed temporal trends in IP chemotherapy use. RESULTS: Overall 12.5% (n = 36) of women received IP chemotherapy during the study period. IP chemotherapy use was non-existent between 2003 and 2005. Use of IP chemotherapy occurred among 26.9% of women diagnosed in 2006 and plateaued at 20.4% of women diagnosed in 2008. IP recipients were younger (mean age 55.9 vs. 63.5 years, p = < 0.001) and more likely to have stage 3 ovarian cancer (77.8 vs. 50.4% p = 0.039) compared to their IV-only chemotherapy counterparts. CONCLUSION: Use of IP chemotherapy for newly diagnosed advanced stage ovarian cancer patients was uncommon in this community setting. Future research should identify potential patient, physician, and system barriers and facilitators to using IP chemotherapy in this setting.

Comparative effectiveness of adjunctive bevacizumab for advanced lung cancer: the cancer research network experience.

INTRODUCTION: Bevacizumab plus carboplatin-paclitaxel (BCP) chemotherapy has Food and Drug Administration approval for advanced nonsquamous, non-small-cell lung cancer based upon improved survival in a clinical trial. However, subgroup analyses of this and other studies have suggested variable results by age and gender. METHODS: Using data from four health maintenance organizations (HMOs) belonging to the Cancer Research Network, 1605 HMO nonsquamous, non-small-cell lung cancer patients aged younger than 21 years, diagnosed 2002-2010, who received carboplatin-paclitaxel (CP), with and without bevacizumab for first-line treatment of stage IIIB/IV disease were identified. Patients were categorized into three groups based on year of diagnosis and regimen during 120 days postdiagnosis: (1) diagnosed 2005-2010 and received BCP; (2) 2005-2010, CP (CP2005), and (3) 2002-2004, CP (CP2002). Survival differences between groups were estimated using Cox proportional hazard models with several propensity score adjustments for demographic, comorbidity, and tumor characteristics. Multivariable subanalyses were also estimated. RESULTS: Median survival was 12.3 months (interquartile range [IQR], 6.0-29.1) for BCP patients versus 8.8 months (IQR, 3.7-21.3) for CP2005 patients and 7.5 months (IQR, 3.8-15.6) for CP2002 patients. In the propensity score-adjusted models, BCP demonstrated a significant survival benefit with a hazard ratio of BCP relative to CP2005 and CP2002 patients of 0.79 (95% confidence interval [CI], 0.66-0.94) and 0.63 (95% CI, 0.52-0.75), respectively. In the multivariable-adjusted subanalyses, relative to the CP2005 cohort, the BCP hazard ratios for patients age less than 65 years, age 65 years old or older, and females were 0.78 (95% CI, 0.62-1.00), 0.74 (95% CI, 0.54-1.00), and 0.77 (95% CI, 0.58-1.00). CONCLUSIONS: In this community-based, comparative effectiveness analysis, we found an overall survival benefit for adults receiving BCP compared with CP.