Real-world comparative effectiveness of palbociclib plus aromatase inhibitor in HR+/HER2- metastatic breast cancer.

Aim: Provide real-world data on palbociclib as evidence of effectiveness in patient populations from routine clinical practice. Methods: This was a retrospective, observational cohort study of patients with HR+/HER2- metastatic breast cancer treated with palbociclib plus aromatase inhibitor (AI) or AI alone as first-line therapy within the US Oncology Network. Results: Patients treated with palbociclib plus AI (n = 838) versus AI alone (n = 450) had a numerically longer median overall survival (42.1 vs 35.7 months; hazard ratio [HR] = 0.90 [95% CI: 0.75-1.07]; p = 0.117) and a significantly extended real-world progression-free survival (21.0 vs 15.7 months; HR = 0.75 [95% CI: 0.64-0.88]; p = 0.0002) after normalized inverse probability treatment weighting. Conclusion: These real-world results support the use of palbociclib plus AI as first-line treatment in routine clinical practice for patients with HR+/HER2- metastatic breast cancer.

What is this summary about? This summary describes how well palbociclib works when used with an aromatase inhibitor in the real-world setting for people with a certain type of breast cancer that has spread to other areas of the body. Palbociclib stops cancer cells from growing and dividing. An aromatase inhibitor prevents the body from making the hormone estrogen, which is needed for certain types of breast cancer cells to grow. Palbociclib with an aromatase inhibitor is a standard first treatment used for people with this type of breast cancer that needs estrogen to grow and has spread to other areas of the body. In clinics, doctors may not always prescribe the two treatments together. The study wanted to find out if using the two treatments together worked better than using an aromatase inhibitor alone in the real-world setting. What were the results? The results suggest that in this population of patients treated in a real-world setting, people with breast cancer that needs estrogen to grow and has spread to other areas of the body who were treated with palbociclib plus an aromatase inhibitor lived longer without their cancer getting worse than those treated with an aromatase inhibitor alone. What do the results of the study mean? The results support the use of palbociclib with an aromatase inhibitor as a first treatment for breast cancer that has spread to other areas of the body, rather than an aromatase inhibitor only.

Durvalumab real-world treatment patterns and outcomes in patients with stage III non-small-cell lung cancer treated in a US community setting.

Background: For eligible patients with unresectable stage III non-small-cell lung cancer, durvalumab consolidation therapy following chemoradiotherapy is the standard of care. Methods: This was a retrospective study of durvalumab-treated patients diagnosed between 1 August 2017 and 29 February 2020. Electronic health record data were assessed descriptively, with Kaplan-Meier methods used for duration of treatment and overall survival (OS). Results: Among 528 patients (median age 70 years, 51.5% male), the median duration of treatment was 7.1 months (95% CI: 6.0-9.0). Estimated 1- and 2-year OS rates were 83.5 and 64.0%, respectively, with median OS not reached. Conclusion: This study confirmed an OS benefit with durvalumab after chemoradiotherapy in a real-world setting, consistent with the results from the PACIFIC phase III clinical trial.

What is this article about? Durvalumab is a treatment approved for patients with a specific type of lung cancer. Clinical trials have shown durvalumab is an effective therapy for these patients. We conducted this study to better understand what happens to patients treated with durvalumab who were not enrolled in clinical trials. What were the results? Patients who were treated with durvalumab in this study tended to survive as long as patients who received it as part of a clinical trial. What do the results of the study mean? Studies like this one may better represent patients who are less likely to take part in clinical trials. Future studies may examine long-term outcomes of durvalumab and factors associated with better outcomes.

Real-World Tumor Response of Palbociclib in Combination With an Aromatase Inhibitor as First-Line Therapy in Pre/Perimenopausal Women With Metastatic Breast Cancer.

BACKGROUND: Limited real-world data exist regarding the efficacy of palbociclib in combination with endocrine therapy in pre/perimenopausal women with metastatic breast cancer. OBJECTIVE: We aimed to compare real-world tumor responses among pre/perimenopausal women who initiated palbociclib plus an aromatase inhibitor (AI) or AI monotherapy as first-line treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. METHODS: This retrospective observational cohort study (NCT05012644) used electronic health record data from The US Oncology Network. Tumor responses were determined based on treating clinicians' assessments of radiologic evidence for changes in disease burden. Normalized inverse probability treatment weighting was used to balance baseline characteristics between treatment cohorts. RESULTS: Of 196 pre/perimenopausal women, 116 and 80 were in the palbociclib plus AI cohort and AI cohort, respectively. Real-world response rates (complete or partial response) were 52.1% and 46.2%, respectively (odds ratio, 1.27 [95% confidence interval 0.72‒2.24]). Among patients with one or more tumor assessments on treatment, real-world response rates were 60.0% in the palbociclib plus AI cohort (n = 103) and 49.9% in the AI cohort (n = 71; odds ratio, 1.51 [95% confidence interval 0.82‒2.77]). CONCLUSIONS: This real-world analysis suggests that pre/perimenopausal patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer appear more likely to respond to palbociclib plus AI versus AI alone as first-line therapy, which may support the combination as a standard-of-care treatment for this patient population.

Palbociclib (Ibrance^®) is a medicine for patients with metastatic breast cancer (MBC). Metastatic means that the cancer has spread to other places in the body. Patients take palbociclib with hormone therapy, such as an aromatase inhibitor (AI). Palbociclib plus an AI is a treatment for a type of MBC called HR+/HER2‒ MBC. HR+/HER2‒ stands for hormone receptor positive, human epidermal growth factor receptor 2 negative. Researchers wanted to observe responses to treatment in routine clinical practice among women with HR+/HER2­ MBC who had not reached menopause. A response is if a tumor shrinks or disappears after treatment. This study used healthcare information reported in electronic medical records of patients seen by doctors in The US Oncology Network. This study included 196 women with HR+/HER2­ MBC who had not reached menopause and had not received prior treatment for MBC. A total of 116 women received palbociclib plus an AI, and 80 women received an AI alone. Researchers used standard statistical approaches to balance baseline characteristics between the two treatment groups. These adjustments made the groups more similar so that researchers could compare treatment responses. Sixty percent of patients who took palbociclib plus an AI responded, compared with 50% of patients who took an AI alone. These results suggest that palbociclib plus an AI may benefit women with HR+/HER2‒ MBC who have not reached menopause.

Real-World Treatment Patterns and Outcomes Among Patients with Basal Cell Carcinoma Following First-Line Hedgehog Inhibitor Discontinuation.

INTRODUCTION: Until recently, patients discontinuing first-line (1L) hedgehog inhibitors (HHIs) for basal cell carcinoma (BCC) had few subsequent treatment options. The objective of this study was to describe the treatment journey and prognosis of patients discontinuing 1L HHI for BCC. METHODS: This was a retrospective cohort study of patients with BCC who discontinued 1L HHI treatment in The US Oncology Network between 1 January 2012 and 1 January 2019 (with follow-up until 1 May 2020). Two cohorts were identified: patients who initiated a second-line (2L) treatment (2L initiators), and patients with 1L progression or toxicity without pathology-confirmed complete response who did not initiate 2L treatment (2L non-initiators). Patient demographics, treatment characteristics, and outcomes are reported for each cohort. RESULTS: Among 115 patients with BCC who received 1L HHI treatment, 63.5% (n = 73/115) discontinued 1L HHIs. Of those, 50.7% (n = 37/73) discontinued because of documented toxicity or progression, without evidence of a complete response. We identified 4 patients who initiated 2L systemic treatment (median age 68.7 years, 100.0% female) and 15 patients who were eligible for the 2L non-initiator cohort (median age 80.2 years, 20.0% female). Median 1L HHI duration was 6.8 months (range 1.9-20.6 months) for the 2L non-initiator cohort and 8.6 months (range 6.8-42.2 months) for 2L initiators. At the end of follow-up, among 2L non-initiators (median follow-up duration 9.7 months), 40.0% were lost to follow-up, 33.3% had died, 20.0% continued observation, and 6.7% transitioned to an academic medical center or hospital; among 2L initiators (median follow-up duration 6.3 months), 50.0% were lost to follow-up, 25.0% had died, and 25.0% continued observation. CONCLUSIONS: Following 1L HHI discontinuation, lack of standardized care and suboptimal outcomes were observed, including limited receipt of 2L treatment. Further studies are necessary to evaluate the impact of newer BCC treatment options.

Pembrolizumab Utilization and Clinical Outcomes Among Patients With Advanced Melanoma in the US Community Oncology Setting: An Updated Analysis.

Favorable outcomes have been observed with pembrolizumab among patients with advanced melanoma in clinical trials; however, limited evidence exists on the long-term efficacy in the real-world setting. This was an updated, retrospective observational study of adult patients with advanced (unresectable or metastatic) melanoma who initiated pembrolizumab (in any line of therapy) between January 1, 2014, and December 31, 2016, in The US Oncology Network and were followed through December 31, 2019 [median follow-up: 18.2 mo (range: 0.1-63.1 mo)]. Study data were sourced from electronic health records. Patient demographic, clinical, and treatment characteristics were assessed descriptively. Kaplan-Meier methods were used to evaluate overall survival (OS), time to treatment discontinuation, time to next treatment, physician-assessed time to tumor progression, and physician-assessed progression-free survival (rwPFS). Independent risk factors for OS and rwPFS were identified with multivariable Cox regression models. Of the 303 study-eligible patients, 119, 131, and 53 received pembrolizumab in the first-line, second-line, and third-line or beyond setting, respectively. Median OS across the study population was 29.3 months [95% confidence interval (CI): 20.3-49.7] and was the longest among those who received first-line pembrolizumab [42.8 mo (95% CI: 24.8-not reached)]. Median rwPFS across the study population was 5.1 months (95% CI: 4.0-7.6) and 8.1 months (95% CI: 4.6-14.4) among those who received first-line pembrolizumab. In the multivariable analyses for OS, increased age, worsening performance status, elevated lactate dehydrogenase, brain metastases, and pembrolizumab use in later lines were significantly associated a worse prognosis.

Treatment patterns and clinical outcomes in patients with advanced non-small cell lung cancer initiating first-line treatment in the US community oncology setting: a real-world retrospective observational study.

PURPOSE: Treatments for advanced non-small cell lung cancer (NSCLC) have evolved to include targeted and immuno-oncology therapies, which have demonstrated clinical benefits in clinical trials. However, few real-world studies have evaluated these treatments in the first-line setting. METHODS: Adult patients with advanced NSCLC who initiated first-line treatment with chemotherapy, targeted therapies (TT), or immuno-oncology-based regimens in the US Oncology Network (USON) between March 1, 2015, and August 1, 2018, were included and followed up through February 1, 2019. Data were sourced from structured fields of USON electronic health records. Patient and treatment characteristics were assessed descriptively, with Kaplan-Meier methods used to evaluate time-to-event outcomes, including time to treatment discontinuation (TTD) and overall survival (OS). Adjusted Cox regression analyses and inverse probability of treatment weighting (IPTW) were performed to control for covariates that may have affected treatment selection and outcomes. RESULTS: Of 7746 patients, 75.6% received first-line systemic chemotherapy, 11.7% received immuno-oncology monotherapies, 8.5% received TT, and 4.2% received immuno-oncology combination regimens. Patients who received immuno-oncology monotherapies had the longest median TTD (3.5 months; 95% confidence interval [CI], 2.8-4.2) and OS (19.9 months; 95% CI, 16.6-24.1). On the basis of multivariable Cox regression and IPTW, immuno-oncology monotherapy was associated with reduced risk of death and treatment discontinuation relative to other treatments. CONCLUSION: These results suggest that real-world outcomes in this community oncology setting improved with the introduction of immuno-oncology therapies. However, clinical benefits are limited in certain subgroups and tend to be reduced compared with clinical trial observations.

Treatment Sequencing Patterns in Patients with Metastatic Urothelial Cancer Treated in the Community Practice Setting in the United States: SPEAR-Bladder (Study informing treatment Pathway dEcision in bladder cAnceR).

PURPOSE: Clinical trial evidence has affirmed the role for immuno-oncology (IO) treatment for locally advanced or metastatic urothelial carcinoma (la/mUC). This Study informing treatment Pathway dEcision in bladder cAnceR (SPEAR-Bladder) aimed to provide insight into the optimal sequencing of IO treatments among la/mUC patients treated in the US Oncology Network. PATIENTS AND METHODS: This was a retrospective analysis of adult patients with la/mUC who initiated first-line chemotherapy followed by either IO therapy (C-IO subgroup) or chemotherapy (C-C subgroup) between 01/01/2015 and 04/30/2017 and included a potential follow-up period through 06/30/2017. Data were sourced from iKnowMed electronic health records. Patient and treatment characteristics were assessed descriptively, with Kaplan-Meier methods used to evaluate time-to-event outcomes, including overall survival (OS). RESULTS: A total of 117 patients were included in this analysis (median age 69 years, 74.4% male, 88.0% Caucasian): 79 and 38 patients were in the C-IO and C-C subgroups, respectively. The median OS was 19.2 months among patients who received the C-IO sequence and 11.9 months among those who received the C-C treatment sequence. CONCLUSION: These results suggest that patients who received the C-IO treatment sequence had notable improvement in OS compared with those who received the C-C sequence. In light of the rapidly evolving therapeutic landscape, further investigation will be required to determine how best to select the optimal therapeutic regimen and sequencing for patients with la/mUC.

An observational study of drug utilization and associated outcomes among adult patients diagnosed with BRAF-mutant advanced melanoma treated with first-line anti-PD-1 monotherapies or BRAF/MEK inhibitors in a community-based oncology setting.

INTRODUCTION: Anti-PD-1 monotherapies (aPD-1) and BRAF/MEK inhibitors (BRAF/MEKi) changed the BRAF-mutant advanced melanoma treatment landscape. This study aimed to improve the understanding of real-world treatment patterns and optimal treatment sequence. METHODS: This was a retrospective study of BRAF-mutant advanced melanoma patients who initiated 1L aPD-1 or BRAF/MEKi in the US Oncology Network between 1 January 2014 and 31 December 2017, followed through 31 December 2018. Patient and treatment characteristics were assessed descriptively, with Kaplan-Meier methods used for time-to-event endpoints. As the primary analysis, overall survival (OS) and physician-assessed progression-free survival (rwPFS) were evaluated with Cox proportional hazard regression models and propensity score matching (n = 49). RESULTS: A total of 224 patients were included (median age 61 years, 62.9% male, 89.7% white): 36.2% received aPD-1 and 63.8% BRAF/MEKi. Median OS and rwPFS were longer among aPD-1 vs BRAF/MEKi patients (OS: not reached vs 13.9 months, log-rank P = .0169; rwPFS: 7.6 vs 6.5 months, log-rank P = .0144). Receipt of aPD-1 was associated with improved OS (HR = 0.602 vs BRAF/MEKi [95%CI 0.382-0.949]; P = .0287). Among patients without an event within 6 months of 1L initiation, receipt of aPD-1 was associated with a decreased risk of progression or death from 6 months onwards (HR = 0.228 [95%CI 0.106-0.493]; P = .0002). This association was not observed among patients within 6 months of 1L initiation (HR = 1.146; 95% CI 0.755-1.738). Results from the propensity score-matched pairs were consistent with these trends. CONCLUSION: These results suggest a clinical benefit of 1L aPD-1 compared to BRAF/MEKi after 6 months of treatment for BRAF-mutant advanced melanoma. Future research should explore factors associated with early progression and their relationship with clinical outcomes.

Treatment Patterns and Healthcare Resource Utilization among Patients with Advanced or Metastatic Soft Tissue Sarcoma in US Community Practices.

INTRODUCTION: This study was designed to describe demographic and clinical characteristics of patients diagnosed with advanced or metastatic soft tissue sarcoma (STS) and to examine treatment and healthcare resource utilization patterns of this patient population in a United States (US) community-based oncology practice setting over time. METHODS AND MATERIALS: A retrospective observational study was conducted within the US Oncology Network (USON). Patients were eligible if they were diagnosed with advanced or metastatic STS and were treated at a USON site between 01 July 2015 and 31 August 2018. Demographic, clinical, and treatment characteristics were described for the overall study population. Comparisons between patients by time period (prior to and after October 2016) were evaluated using the T test for continuous variables and chi-squared test for categorical variables. Data were available for analysis through 31 August 2018. RESULTS: Demographic and clinical characteristics of the eligible study cohort (N = 376) were similar between patients who initiated treatment before and after October 2016 (all p > 0.05). Forty-three unique regimens were observed in the first-line setting, with the predominant regimen (gemcitabine + docetaxel) received by 33.2% (n = 125) patients. Prior to October 2016, 45.4% of patients received first-line gemcitabine + docetaxel, while 29.0% received this regimen after October 2016. CONCLUSIONS: While demographic and clinical characteristics were similar, treatment patterns changed in 2016. Future research should evaluate the impact of changing drug approvals and clinical trial results on future treatment patterns.

Real-world treatment patterns and clinical outcomes among patients with advanced melanoma: A retrospective, community oncology-based cohort study (A STROBE-compliant article).

Recently, the effectiveness of novel immune checkpoint inhibitors and BRAF-directed therapies has been demonstrated in advanced melanoma trial populations. Limited research, however, has evaluated the impact of these therapies in a real-world setting. The aim of this study was to evaluate treatment patterns and clinical outcomes among advanced melanoma patients treated with modern therapies within community oncology clinics. Adult patients with advanced melanoma who initiated treatment within the US Oncology Network between 1/1/14 and 12/31/16 were included. Data were sourced from electronic healthcare records. Patients were followed through 12/31/17. Descriptive analyses were performed to assess patient and treatment characteristics and Kaplan-Meier methods were used for time-to-event outcomes. In total, 484 patients met eligibility criteria (32.0% with brain metastasis, 12.6% with Eastern Cooperative Oncology Group performance status ≥2). In the first-line (1L) setting during the study period, 37.0% received anti-PD1 monotherapies, 26.4% ipilimumab monotherapy, 19.8% BRAF/MEK combination therapy, 6.4% BRAF or MEK monotherapy, 4.1% ipilimumab/nivolumab combination therapy and 6.2% other regimens. Differences in baseline demographic and clinical characteristics were observed across treatment groups. For the overall study population, the median (95% confidence interval) estimates for overall survival, time to next treatment and progression-free survival were 20.7 (16.0, 26.8), 5.8 (5.3, 6.5), and 4.9 (4.2, 5.7) months, respectively. The results of this study provide real-world insight into advanced melanoma treatment trends and clinical outcomes, including high utilization of immunotherapies and BRAF/MEK combination therapy. Future research can explore underlying differences in patient subpopulations and the sequence of therapies across lines of therapy.

Daratumumab Split First Versus Single Dosing Schedule Among Patients With Multiple Myeloma Treated in a US Community Oncology Setting: A Retrospective Observational Study.

PURPOSE: Daratumumab was initially approved by the US Food and Drug Administration to be given intravenously over the course of several hours during each administration. Because the duration of the first dose can exceed 7 h, the US Oncology Network developed a split first dose schedule to administer the first administration (dose) over 2 consecutive days. METHODS: This trial was a retrospective cohort study of adult multiple myeloma (MM) patients who initiated daratumumab within the US Oncology Network between November 1, 2015, and June 30, 2017. Descriptive analyses were conducted to compare split dose versus single-dose groups, and a multivariable linear regression model was developed to identify factors associated with total administration time. FINDINGS: In total, 622 patients were included in the analysis (364 split first dose patients and 258 single-dose patients). Infusion reactions to the first administration were documented for 47.8% of split first dose patients and 48.3% of single-dose patients. Among the total study population, the most common reactions were lower respiratory tract-related reactions (26.1%), upper respiratory tract-related reactions (17.2%), and gastrointestinal adverse events (12.5%), with no statistically significant differences between groups. The median infusion duration was 4.5 h for day 1 of the split first dose and 6.5 h for the single dose (P < 0.0001); the total median infusion time was 8.7 h for the split first dose. In multivariable regression, the only factor associated with infusion time was dosing schedule. IMPLICATIONS: These results provide real-world evidence regarding the safety and infusion time of the first infusion of daratumumab. Although the total administration time was longer among patients receiving a split first dose, the shorter day 1 infusion for this dosing schedule without increased infusion reactions may be an option for community oncology clinics.

A real-world comparative analysis of carfilzomib and other systemic multiple myeloma chemotherapies in a US community oncology setting.

BACKGROUND: Most multiple myeloma (MM) patients ultimately progress, with remission duration decreasing after first relapse. Recently, novel agents have been approved for the treatment of relapsed MM. There is a paucity of real-world data on these treatments. We sought to compare time to next treatment (TTNT) in MM patients in their second line of therapy (LOT2), treated with common proteasome inhibitor (PI)-based triplets. METHODS: Adult MM patients who received carfilzomib (K) between 1 November 2013 and 29 February 2016 at US Oncology Network (USON) clinics utilizing iKnowMed™ electronic health records (EHRs) were identified. Patients were included if they were ⩾18 years of age, not enrolled in clinical trials, had ⩾2 visits at a USON clinic and received LOT2 regimens consisting of: K+lenalidomide with steroid (KRd), bortezomib+lenalidomide with steroid (VRd), or bortezomib+cyclophosphamide with steroid (VCyd). TTNT was estimated from LOT2 initiation to LOT3 initiation using the Kaplan-Meier method, and hazard ratios (HRs) were estimated using Cox modeling. RESULTS: A total of 718 patients received a K-containing regimen sometime during their MM treatment (LOT1 to LOT5). Of these, 156 patients received: KRd (n = 112; 71.8%), VRd (n =27; 17.3%), or VCyd (n = 17; 10.9%). Baseline characteristics were similar between groups (mean age: 64.8 years; 58% male). Median TTNT was longest for KRd [25.3 months; 95% confidence interval (CI): 19.71-NR], versus VRd or VCyd (VRd median TTNT: 10.2 months, 95% CI: 4.24-12.71; VCyd: 6.5 months, 95% CI: 3.02-12.78; log-rank p < 0.0001). The adjusted HR for KRd was 0.19 (95% CI: 0.11-0.37), compared with VRd. CONCLUSIONS: Considering the real-world nature of these data, the median TTNT observed with KRd was relatively consistent, with progression-free survival (PFS) for KRd observed in the phase III ASPIRE trial (median PFS: ITT population = 26.3 months; LOT2 = 29.6 months). Patients who received KRd at first relapse had significantly longer TTNT, compared with those on VRd or VCyd, confirming the value of KRd as an important treatment option for relapsed MM.

Treatment Patterns by EGFR Mutation Status in Non-Small Cell Lung Cancer Patients in the USA: A Retrospective Database Analysis.

INTRODUCTION: Targeted therapies, including tyrosine kinase inhibitors (TKIs) that target the sensitizing epidermal growth factor receptor (EGFR) gene are recommended for patients with non-small cell lung cancer (NSCLC). Most patients with NSCLC who test positive for the EGFR mutation and receive TKIs develop resistance to these drugs. Questions remain regarding which treatment sequence is optimal for patients with EGFR-mutant NSCLC, and few studies have evaluated patterns of TKI treatment use in NSCLC, irrespective of EGFR mutation status, in a real-world setting. This population-based study aimed to evaluate treatment patterns at a national level in the USA. METHODS: This retrospective observational study used data from the US Oncology Network's iKnowMed database. Patients with advanced NSCLC who initiated first-line therapy with erlotinib and/or intravenous chemotherapy between January 1, 2012 and June 30, 2015 and met all other study criteria were included. Descriptive analyses assessed demographic and clinical characteristics and treatment patterns among the overall study cohort, as well as for specific erlotinib treatment subgroups, stratified by EGFR status. RESULTS: Among the 3108 patients identified, 18.5% were EGFR positive, 49.8% were EGFR negative, and 31.7% were EGFR documented unknown. For the overall cohort, 18.4% received first-line erlotinib monotherapy, fewer than 1% received first-line combination therapy (erlotinib plus chemotherapy), 4.7% received second-line erlotinib monotherapy, and 3.3% received second-line combination therapy. First-line erlotinib monotherapy was used in 77.8% of all EGFR positive patients. Almost two-thirds of the overall cohort were not observed to have advanced to second-line therapy. CONCLUSIONS: As treatment options evolve, this study provides real-world treatment patterns that suggest concordance with NCCN guidelines and confirm the remaining need to understand sequencing of therapies and related outcomes. FUNDING: Eli Lilly and Company.

Ramucirumab for the treatment of patients with gastric or gastroesophageal junction cancer in community oncology practices.

BACKGROUND: Limited real-world research has investigated ramucirumab for the treatment of patients with gastric or gastroesophageal junction (GEJ) cancer. This study was designed to describe ramucirumab monotherapy or combination therapy use in a community oncology practice setting. METHODS: This was a retrospective observational cohort study to describe the treatment of adult patients with gastric or GEJ cancer who initiated ramucirumab treatment between 4/21/14 and 6/30/16 within the US Oncology Network. Kaplan-Meier method and Cox proportional hazards regression analyses were used to assess clinical outcomes. Multivariable logistic regression models were used to assess patient-level predictors of ramucirumab monotherapy or combination therapy. RESULTS: A total of 505 patients (mean age 64.4 years; 75.1% male) were included in the analysis; subgroups included: monotherapy (22.8%; n = 115), combination therapy (77.2%; n = 390). Monotherapy patients were significantly older (67.7 vs. 63.4 years; P = 0.0006), received ramucirumab approximately 3 months later after diagnosis (16.9 vs. 14.1 months; P = 0.0318) and more frequently initiated ramucirumab in the third or later lines of treatment (38.3 vs. 8.2%; P<0.0001) than patients receiving combination therapy. Median overall survival (OS) for monotherapy and combination therapy from the start of second-line therapy was 5.5 months (confidence interval [CI] 4.3, 7.8) and 7.4 months (CI 6.6, 8.8), respectively. CONCLUSIONS: The results showed that patients who received ramucirumab monotherapy started ramucirumab therapy later after diagnosis and were older than those who received ramucirumab in combination. Additionally, survival data suggest that outcomes observed in community oncology practices are similar to data from phase 3 clinical trials.

Value-Based Benefit Design to Improve Medication Adherence for Employees with Anxiety or Depression.

BACKGROUND: Through reduced out-of-pocket costs and wellness offerings, value-based benefit design (VBBD) is a promising strategy to improve medication adherence and other health-related outcomes across populations. There is limited evidence, however, of the effectiveness of these policy-level changes among individuals with anxiety or depression. OBJECTIVES: To assess the impact of a multifaceted VBBD policy that incorporates waived copayments, wellness offerings, and on-site services on medication adherence among plan members with anxiety or depression, and to explore how this intervention and its resulting improved adherence affects other health-related outcomes. METHODS: A retrospective longitudinal pre/post design was utilized to measure outcomes before and after the VBBD policy change. Repeated measures statistical regression models with correlated error terms were utilized to evaluate outcomes among employees of a self-insured global health company and their spouses (N = 529) who had anxiety or depression after the VBBD policy change. A multivariable linear regression model was chosen as the best fit to evaluate a change in medication possession ratio (MPR) after comparing parameters for several distributions. The repeated measures multivariable regression models were adjusted for baseline MPR and potential confounders, including continuous age, sex, continuous modified Charlson Comorbidity Index, and the continuous number of prescriptions filled that year. The outcomes were assessed for the 1 year before the policy change (January 1, 2011, through December 31, 2011) and for 2 years after the change (January 1, 2012, through December 31, 2013). The primary outcome was a change in MPR. The secondary outcomes included healthcare utilization, medical or pharmacy costs, the initiation of medication, generic medication use, and employee absenteeism (the total number of sick days). RESULTS: The implementation of the VBBD strategy was associated with a significant increase in average MPR (0.65 vs 0.61 in the pre-VBBD period; P = .004), the initiation of new medications for anxiety or depression (31.4% vs 29.5%, respectively; P = .033), and the filling of generic medications for anxiety or depression (85.1% vs 80.5%, respectively; P <.001). A multivariable adjusted analysis revealed a 0.05 increase in MPR after the benefit enhancement (P = .002). Healthcare utilization, costs, and absenteeism were not statistically different before and after the VBBD policy change. CONCLUSION: The VBBD strategy was associated with improved medication adherence and cost-conscious medication use. Future analyses should explore whether these trends persist over time, and if they can further impact healthcare utilization, cost, and absenteeism.

Impact of Employer-Sponsored Onsite Pharmacy and Condition Management Programs on Medication Adherence.

BACKGROUND: Poor medication adherence is associated with worsened health outcomes and higher health care expenditures. An increasing number of employers are sponsoring wellness initiatives designed to support healthy lifestyles, improve productivity, and offer a return on investment. Onsite pharmacies may facilitate higher medication adherence rates by providing employees a convenient, low-cost option for filling prescriptions that is integrated with other onsite health services. OBJECTIVES: To (a) assess the impact of an employer's onsite pharmacy on health plan members' medication adherence using multiple measures of medication adherence and persistence, including medication possession ratio (MPR), average number of days until discontinuation (60-day gap in coverage), and percentage of members without a 30-day gap in coverage, and (b) evaluate these outcomes between those members who participated in condition management programs and those who did not. METHODS: A retrospective analysis of a self-insured employer's claims data was undertaken. Medication adherence was assessed among the self-insured employer's health plan members, which included subscribers and their dependents who filled an asthma, depression, diabetes, hypertension, or hyperlipidemia medication at an onsite pharmacy, compared with those who used a community pharmacy. Multiple standard measures of medication adherence were considered. These measures included MPR, which was assessed for 1- and 2-year time periods. MPR was chosen because it is one of the most commonly referenced formulas in the literature and represents adherence over a fixed period of time. In addition, medication persistence was estimated by 30-day gaps in coverage and discontinuation of treatment. To assess the impact of onsite pharmacy use and account for covariate effects, the linear mixed model approach was applied with the logit transformed MPR as the response variable. An analysis of MPR among condition management participants was also performed. RESULTS: In total, 2,498 subscribers and their dependents were included in the analysis. The average MPR at 365 days was significantly higher (P < 0.0001) among onsite pharmacy users for all medication types, ranging from 13% higher for depression medications to 20% higher for hypertension medications. This trend persisted at 730 days (P < 0.001), with average MPRs ranging from 6% higher for hyperlipidemia medications to 11% higher for hypertension medications. A mixed model analysis indicated that members who used the onsite pharmacy were 3.44 times more likely to demonstrate medication adherence (95% CI = 2.84-4.16; P < 0.0001) at 365 days. Likewise, at 180 and 365 days, onsite pharmacy users were less likely to have 30-day gaps in treatment. The average number of days until discontinuation (defined as a 60-day gap) was also significantly longer (P < 0.0001) among onsite pharmacy users, ranging from an average of 56 additional days for depression medications to 105 additional days for hypertension medications. While the average MPR tended to be higher among those subscribers and their dependents who participated in condition management programs, this trend was not statistically significant for all medication types. CONCLUSIONS: Based on multiple measures, onsite pharmacy use was associated with higher medication adherence, while the results were inconclusive for condition management participation.

Bringing care home: how telemonitoring can expand population health management beyond the hospital.

With emerging technology, patients are able to access the health care system from settings such as their homes, long-term care facilities, and schools. Telemonitoring allows care teams to oversee patients' clinical data captured and transmitted by specialized devices, with minimal involvement or manual effort, on a near real-time basis. This review was undertaken to provide insight into the capacity of telemonitoring technology to improve population health. Despite the potential of telemonitoring, evidence for its clinical, economic, and patient-reported benefits is inconclusive. Much of the outcome variation seen in the literature may be due to the heterogeneity of the interventions' characteristics, with some telemonitoring programs more effectively integrating into standard practice, targeting patients, and utilizing technology. A particular challenge is the ability to comprehensively leverage data to improve health outcomes. To accomplish this, the mass data collected by the devices must be aggregated with data from other clinical systems and used to develop predictive algorithms that can be embedded across the continuum of care. Innovations such as the Healthe Intent cloud-based platform can support a population health strategy by integrating telemonitoring and electronic health record data.

Men with celiac disease are shorter than their peers in the general population.

OBJECTIVE: Late diagnosis of celiac disease (CD) is increasingly common, the implications of which are largely unknown. Although short stature is a common sign of childhood CD, the data on the height of adult CD patients is conflicting. This study investigates the final height of men and women diagnosed with CD in adulthood and attempts to identify influencing factors. PATIENTS AND METHODS: We performed a cross-sectional study of 585 adults at the Celiac Disease Center at Columbia University, comparing their height with the control population (NHANES). Patients were included if they were older than 18 years of age at diagnosis and if baseline height and weight were available. In addition, we examined for differences in demographic and physical features, mode of presentation, and concomitant illnesses in shorter versus taller celiac patients. RESULTS: Men (n=162) with CD diagnosed in adulthood were shorter than men in the general population (CD: 169.3 ± 10.5 vs. 177.3 ± 7.0 cm, P<0.01) whereas women (n=423) were not (CD: 166.3 ± 9.4 vs. 163.2 ± 6.7 cm). There were no statistically significant differences in age at diagnosis, BMI, concomitant autoimmune illnesses (hypothyroidism, type I diabetes, dermatitis herpetiformis), or mode of presentation in shorter versus taller CD patients of either sex. Hemoglobin was associated with short stature in CD men (short: 13.9 g/dl, tall: 14.6 g/dl; P=0.01), but not women (short: 12.9 g/dl, tall: 13.0 g/dl, P=0.41). CONCLUSION: Short stature is a well described phenomenon in pediatric CD with the potential for 'catch-up growth' on a gluten-free diet. However, among adults with CD who had attained final height before diagnosis, we found that men, not women, are shorter relative to the general population.

Should intussusception in children prompt screening for celiac disease?

OBJECTIVES: An association between adult celiac disease (CD) and intussusceptions (ISs) has been described. Although more common among children, intussusception has not been linked with childhood CD aside from isolated case reports. Our aim was to investigate the frequency of IS among children with CD. METHODS: A patient database containing children with biopsy-proven CD was reviewed, in addition to radiology records contained in a hospital-maintained clinical data repository. RESULTS: Of 254 children with biopsy-proven CD and complete records available for review, abdominal imaging was performed in 21%, mainly because of abdominal pain. Among children with CD, 1.2% experienced an IS <9 months before their diagnosis with CD. Among children seen at our institution in the same time period, 0.07% experienced an IS. The majority of those children with CD who were found to have IS had no evidence of nutritional deficit at the time of IS. IS was not identified in any children with CD who had been treated with a gluten-free diet. CONCLUSIONS: IS was far more common among children in our cohort with untreated CD than in the general pediatric population simultaneously seen at our center. The diagnosis of CD should be considered in children with IS, even in the absence of signs of nutritional compromise.

Patch clamp recordings in inner ear hair cells isolated from zebrafish.

Patch clamp analyses of the voltage-gated channels in sensory hair cells isolated from a variety of species have been described previously(1-4) but this video represents the first application of those techniques to hair cells from zebrafish. Here we demonstrate a method to isolate healthy, intact hair cells from all of the inner ear end-organs: saccule, lagena, utricle and semicircular canals. Further, we demonstrate the diversity in hair cell size and morphology and give an example of the kinds of patch clamp recordings that can be obtained. The advantage of the use of this zebrafish model system over others stems from the availability of zebrafish mutants that affect both hearing and balance. In combination with the use of transgenic lines and other techniques that utilize genetic analysis and manipulation, the cell isolation and electrophysiological methods introduced here should facilitate greater insight into the roles hair cells play in mediating these sensory modalities.