Clinical and Genomic Characteristics of Patients with Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer Following Progression on Cyclin-Dependent Kinase 4 and 6 Inhibitors.

PURPOSE: We explored the clinical and genomic characteristics of hormone receptor-positive (HR+), HER2-negative (HER2-) metastatic breast cancer (MBC) after progression on cyclin-dependent kinase 4 and 6 inhibitors (CDK4 and 6i) ± endocrine therapy (ET) to understand potential resistance mechanisms that may aid in identifying treatment options. EXPERIMENTAL DESIGN: Patients in the United States with HR+, HER2- MBC had tumor biopsies collected from a metastatic site during routine care following progression on a CDK4 and 6i ± ET (CohortPost) or prior to initiating CDK4 and 6i treatment (CohortPre) and analyzed using a targeted mutation panel and RNA-sequencing. Clinical and genomic characteristics were described. RESULTS: The mean age at MBC diagnosis was 59 years in CohortPre (n = 133) and 56 years in CohortPost (n = 223); 14% and 45% of patients had prior chemotherapy/ET, and 35% and 26% had de novo stage IV MBC, respectively. The most common biopsy site was liver (CohortPre, 23%; CohortPost, 56%). CohortPost had significantly higher tumor mutational burden (TMB; median 3.16 vs. 1.67 Mut/Mb, P < 0.0001), ESR1 alteration frequency (mutations: 37% vs. 10%, FDR < 0.0001; fusions: 9% vs. 2%, P = 0.0176), and higher copy-number amplification of genes on chr12q15, including MDM2, FRS2, and YEATS4 versus patients in the CohortPre group. In addition, CDK4 copy-number gain on chr12q13 was significantly higher in CohortPost versus CohortPre (27% vs. 11%, P = 0.0005). CONCLUSIONS: Distinct mechanisms potentially associated with resistance to CDK4 and 6i ± ET, including alterations in ESR1 and amplification of chr12q15 and CDK4 copy-number gain, were identified.

Clinicogenomic factors and treatment patterns among patients with advanced non-small cell lung cancer with or without brain metastases in the United States.

BACKGROUND: This retrospective, real-world study evaluated the prevalence of brain metastases, clinicodemographic characteristics, systemic treatments, and factors associated with overall survival among patients with advanced non-small cell lung cancer (aNSCLC) in the US. We also described the genomic characterization of 180 brain metastatic specimens and frequency of clinically actionable genes. MATERIALS AND METHODS: De-identified electronic health records-derived data of adult patients diagnosed with aNSCLC between 2011 and 2017 were analyzed from a US-nationwide clinicogenomic database. RESULTS: Of 3257 adult patients with aNSCLC included in the study, approximately 31% (n = 1018) had brain metastases. Of these 1018 patients, 71% (n = 726) were diagnosed with brain metastases at initial NSCLC diagnosis; 57% (n = 583) of patients with brain metastases received systemic treatment. Platinum-based chemotherapy combinations were the most common first-line therapy; single-agent chemotherapies, epidermal growth factor receptor tyrosine kinase inhibitors, and platinum-based chemotherapy combinations were used in second line. Patients with brain metastases had a 1.56 times greater risk of death versus those with no brain metastases. In the brain metastatic specimens (n = 180), a high frequency of genomic alterations in the p53, MAPK, PI3K, mTOR, and cell-cycle associated pathways was observed. CONCLUSION: The frequency of brain metastases at initial clinical presentation and associated poor prognosis for patients in this cohort underscores the importance of early screening for brain metastasis in NSCLC. Genomic alterations frequently identified in this study emphasize the continued need for genomic research and investigation of targeted therapies in patients with brain metastases.

Real-world ramucirumab and immune checkpoint inhibitor sequences in US patients with advanced gastroesophageal cancer.

Aim: To describe real-world treatment sequences of ramucirumab relative to immune checkpoint inhibitors (ICIs) in patients with advanced gastroesophageal cancer. Methods: Retrospective, observational study including adult patients treated with ramucirumab (April 2014-June 2020) from a nationwide health-record database. Results: In 1117 eligible patients, ramucirumab + paclitaxel was the most common ramucirumab-containing regimen (72.0%). A total of 217 patients also received an ICI. For ramucirumab then ICI (n = 148) and ICI then ramucirumab (n = 50), ramucirumab + taxane and ICI monotherapy were the most frequent approaches, most commonly observed as second- and third-line (2L and 3L). Median time on ramucirumab in 2L and 3L was similar regardless of sequence with ICI. Conclusion: Most patients with advanced gastroesophageal cancer received ramucirumab before ICI, with ramucirumab + paclitaxel as the most common ramucirumab-based regimen.

What is the Order of New Treatments for Gastroesophageal Cancers in the Real World? What is this summary about? Gastroesophageal cancers (cancers of the stomach or food pipe) which cannot be cured are first treated using traditional chemotherapy. Newer anti-cancer therapies with fewer side effects, such as ramucirumab (RAM) and immune checkpoint inhibitors (ICI), are now available either alone or in combination with chemotherapy. We designed this study to describe the order of use for RAM and ICI. What were the results? The patients in this study were from Flatiron Health database, which includes electronic medical record data of US patients with gastroesophageal cancers. The included patients had been treated with RAM and were grouped based on the treatments received and in the order in which they received RAM and ICI. Of the patients who received both RAM and ICI, RAM then ICI was the most common order, followed by ICI then RAM and then RAM plus ICI at the same time. RAM in combination with paclitaxel (a chemotherapy) was the most common RAM-containing treatment. The duration of RAM therapy was the same whether patients received the treatment before or after ICI. What do results of the study mean? These findings can be used by patients with gastroesophageal cancers and oncologists when making treatment decisions, specifically if RAM might be an option when it is time to change treatments. Real-world studies like this help answer questions that were not addressed in clinical trials.

Development and Validation of Coding Algorithms to Identify Patients with Incident Non-Small Cell Lung Cancer in United States Healthcare Claims Data.

Purpose: We sought to develop and validate an incident non-small cell lung cancer (NSCLC) algorithm for United States (US) healthcare claims data. Diagnoses and procedures, but not medications, were incorporated to support longer-term relevance and reliability. Methods: Patients with newly diagnosed NSCLC per Surveillance, Epidemiology, and End Results (SEER) served as cases. Controls included newly diagnosed small-cell lung cancer and other lung cancers, and two 5% random samples for other cancer and without cancer. Algorithms derived from logistic regression and machine learning methods used the entire sample (Approach A) or started with a previous algorithm for those with lung cancer (Approach B). Sensitivity, specificity, positive predictive values (PPV), negative predictive values, and F-scores (compared for 1000 bootstrap samples) were calculated. Misclassification was evaluated by calculating the odds of selection by the algorithm among true positives and true negatives. Results: The best performing algorithm utilized neural networks (Approach B). A 10-variable point-score algorithm was derived from logistic regression (Approach B); sensitivity was 77.69% and PPV = 67.61% (F-score = 72.30%). This algorithm was less sensitive for patients ≥80 years old, with Medicare follow-up time <3 months, or missing SEER data on stage, laterality, or site and less specific for patients with SEER primary site of main bronchus, SEER summary stage 2000 regional by direct extension only, or pre-index chronic pulmonary disease. Conclusion: Our study developed and validated a practical, 10-variable, point-based algorithm for identifying incident NSCLC cases in a US claims database based on a previously validated incident lung cancer algorithm.

Development and Evaluation of the Algorithm CErtaInty Tool (ACE-IT) to Assess Electronic Medical Record and Claims-based Algorithms' Fit for Purpose for Safety Outcomes.

INTRODUCTION: Electronic health record (EHR) or medical claims-based algorithms (i.e., operational definitions) can be used to define safety outcomes using real-world data. However, existing tools do not allow researchers and decision-makers to adequately appraise whether a particular algorithm is fit for purpose (FFP) to support regulatory decisions on drug safety surveillance. Our objective was to develop a tool to enable regulatory decision-makers and other stakeholders to appraise whether a given algorithm is FFP for a specific decision context. METHODS: We drafted a set of 77 generic items informed by regulatory guidance documents, existing instruments, and publications. The outcome of ischemic stroke served as an exemplar to inform the development of draft items. The items were designed to be outcome independent. We conducted a three-round online Delphi panel to develop and refine the tool and achieve consensus on items (> 70% agreement) among panel participants composed of regulators, researchers from pharmaceutical organizations, academic clinicians, methodologists, pharmacoepidemiologists, and cardiologists. We conducted a qualitative analysis of panel responses. Five pairs of reviewers independently evaluated two ischemic stroke algorithm validation studies to test its application. We developed a user guide, with explanation and elaboration for each item, guidance on essential and additional elements for user responses, and an illustrative example of a complete assessment. Furthermore, we conducted a 2-h online stakeholder panel of 16 participants from regulatory agencies, academic institutions, and industry. We solicited input on key factors for an FFP assessment, their general reaction to the Algorithm CErtaInty Tool (ACE-IT), limitations of the tool, and its potential use. RESULTS: The expert panel reviewed and made changes to the initial list of 77 items. The panel achieved consensus on 38 items, and the final version of the ACE-IT includes 34 items after removal of duplicate items. Applying the tool to two ischemic stroke algorithms demonstrated challenges in its application and identified shared concepts addressed by more than one item. The ACE-IT was viewed positively by the majority of stakeholders. They identified that the tool could serve as an educational resource as well as an information-sharing platform. The time required to complete the assessment was identified as an important limitation. We consolidated items with shared concepts and added a preliminary screen section and a summary assessment box based on their input. The final version of the ACE-IT is a 34-item tool for assessing whether algorithm validation studies on safety outcomes are FFP. It comprises the domains of internal validity (24 items), external validity (seven items), and ethical conduct and reporting of the validation study (three items). The internal validity domain includes sections on objectives, data sources, population, outcomes, design and setting, statistical methods, reference standard, accuracy, and strengths and limitations. The external validity domain includes items that assess the generalizability to a proposed target study. The domain on ethics and transparency includes items on ethical conduct and reporting of the validation study. CONCLUSION: The ACE-IT supports a structured, transparent, and flexible approach for decision-makers to appraise whether electronic health record or medical claims-based algorithms for safety outcomes are FFP for a specific decision context. Reliability and validity testing using a larger sample of participants in other therapeutic areas and further modifications to reduce the time needed to complete the assessment are needed to fully evaluate its utility for regulatory decision-making.

Causal analyses with target trial emulation for real-world evidence removed large self-inflicted biases: systematic bias assessment of ovarian cancer treatment effectiveness.

BACKGROUND AND OBJECTIVES: Drawing causal conclusions from real-world data (RWD) poses methodological challenges and risk of bias. We aimed to systematically assess the type and impact of potential biases that may occur when analyzing RWD using the case of progressive ovarian cancer. METHODS: We retrospectively compared overall survival with and without second-line chemotherapy (LOT2) using electronic medical records. Potential biases were determined using directed acyclic graphs. We followed a stepwise analytic approach ranging from crude analysis and multivariable-adjusted Cox model up to a full causal analysis using a marginal structural Cox model with replicates emulating a reference randomized controlled trial (RCT). To assess biases, we compared effect estimates (hazard ratios [HRs]) of each approach to the HR of the reference trial. RESULTS: The reference trial showed an HR for second line vs. delayed therapy of 1.01 (95% confidence interval [95% CI]: 0.82-1.25). The corresponding HRs from the RWD analysis ranged from 0.51 for simple baseline adjustments to 1.41 (95% CI: 1.22-1.64) accounting for immortal time bias with time-varying covariates. Causal trial emulation yielded an HR of 1.12 (95% CI: 0.96-1.28). CONCLUSION: Our study, using ovarian cancer as an example, shows the importance of a thorough causal design and analysis if one is expecting RWD to emulate clinical trial results.

Real-World Patient Characteristics, Utilization Patterns, and Outcomes of US Patients with HR+, HER2- Metastatic Breast Cancer Treated with Abemaciclib.

BACKGROUND: Abemaciclib is the most recent oral cyclin-dependent kinase 4 and 6 inhibitor (CDK4 & 6i) to receive US Food and Drug Administration (FDA) approval to treat hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer (MBC). Administrative claims data were used to describe patient characteristics and select clinical and economic outcomes in US patients treated in routine clinical practice. Prior analyses from electronic health records data indicate approximately 25% of patients received either palbociclib or ribociclib for MBC before initiating abemaciclib treatment; this work further explored these findings and associated outcomes. METHODS: This retrospective study analyzed medical and pharmacy claims from the IBM® MarketScan® Research Databases between 1 January 2007 to 31 January 2020. Patients with HR+, HER2- MBC newly initiating abemaciclib between 1 September 2017 and 31 October 2019 were included and grouped by concomitant therapy (+aromatase inhibitor (AI), +fulvestrant (F), 200 mg abemaciclib monotherapy (Mono), or +other), and outcomes were analyzed by prior CDK4 & 6i use. Patient and treatment characteristics were summarized with descriptive statistics. Kaplan-Meier methods assessed time-to-discontinuation (TTD; i.e., persistency) and time-to-chemotherapy (TTC). Adherence (defined by the medication possession ratio) and drug wastage were determined. RESULTS: This analysis included 454 patients (mean age 57.7 years), with 35.0% (n = 159) in the +F group, 29.3% (n = 133) in the +AI group, 10.4% (n = 47) in the 200 mg Mono group, and 25.3% (n = 115) in the +other group. Prior chemotherapy and CDK 4 & 6i use were present in 23.8% and 49.8% of all patients, respectively. Visceral metastases were present at abemaciclib initiation in 50.4% in the +AI group; 49.7% in the +F group; and 55.3% in the 200 mg Mono group. Liver metastases were present in 33.7% of the overall population. Among patients without prior CDK4 & 6i use, the median TTD for patients receiving abemaciclib + AI was not reached [95% CI 430-not reached (NR) days], abemaciclib + F [531 days (95% CI 281-NR)], and abemaciclib mono [141 days (95% CI 80-NR)]. Median TTC for abemaciclib + AI and abemaciclib + F groups were not reached and the median TTC for abemaciclib mono was 535 days (95% CI 181-NR). Medication adherence was 88.7% and medication wastage costs among those with at least one dose modification were $808.12 and $452.2 per patient per month based on amount paid and wholesale acquisition cost (WAC), respectively. Mean length of follow-up for all patients was 350 days (SD 187). CONCLUSION: These real-world data complement clinical trial results by examining abemaciclib use among patients treated in routine clinical practice. The sizeable number of patients treated with prior CDK4 & 6i, chemotherapy, and/or visceral metastases at abemaciclib initiation suggest that many patients had very advanced disease and/or were in later stages of their treatment. These data confirm a higher percentage of patients treated with previous CDK4 & 6i than reported previously, reinforcing the importance of the ongoing, prospective clinical trials evaluating outcomes following progression on CDK4 & 6i.

A review of stakeholder recommendations for defining fit-for-purpose real-world evidence algorithms.

Aim: The credibility and value of real-world evidence (RWE) are either supported or undermined by the algorithms (i.e., operational definitions) used. Methods: We conducted a targeted evidence review of key RWE decision makers' published recommendations on RWE algorithms through April 2021. Stakeholders were regulatory bodies, other governmental agencies and payer organizations. Results: Our review identified recommended criteria: relevance, validity, reliability, responsiveness, transparency and replicability, safety, feasibility and quality process. Stakeholders routinely recommended accuracy measures, subgroups evaluation and specific considerations for assessing exposures and covariates and the underlying real-world data (RWD) quality. Conclusion: The importance of stakeholder guidance on fit-for-purpose RWE algorithms is growing. We highlight gaps that future guidance and stakeholder recommendations could address.

Real-world characteristics and outcomes of advanced non-small-cell lung cancer patients with EGFR exon 19 deletions or exon 21 mutations.

Aim: To estimate real-world (rw) outcomes for first-line therapy in patients with advanced EGF receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC), focusing on specific mutation types. Patients & methods: Retrospective observational study (n = 244 patients). Results: Univariate/multivariate analyses showed longer rw progression-free survival (rwPFS) and rwPFS2 in patients with ex19del versus Leu858Arg mutations. Median overall survival was 12.3 months longer with ex19del versus Leu858Arg mutations (HR: 1.47 [95% CI: 0.96-2.25]; p = 0.074). With EGFR-tyrosine kinase inhibitor monotherapy, unadjusted rwPFS for ex19del mutations was longer than for Leu858Arg mutations (HR: 1.62 [95% CI: 1.03-2.56]; p = 0.036). Conclusion: In this rw cohort of patients with advanced EGFR+ NSCLC, ex19del mutations conferred a prognostic advantage over Leu858Arg mutations, with significantly better rwPFS and rwPFS2.

Validation of an International Classification of Disease, 10th revision coding adaptation for the Charlson Comorbidity Index in United States healthcare claims data.

PURPOSE: An International Classification of Disease (ICD-10) Charlson Comorbidity Index (CCI) adaptation had not been previously developed and validated for United States (US) healthcare claims data. Many researchers use the Canadian adaption by Quan et al (2005), not validated in US data. We sought to evaluate the predictive validity of a US ICD-10 CCI adaptation in US claims and compare it with the Canadian standard. METHODS: Diverse patient cohorts (rheumatoid arthritis, hip/knee replacement, lumbar spine surgery, acute myocardial infarction [AMI], stroke, pneumonia) in the IBM® MarketScan® Research Databases were linked with the IBM MarketScan Mortality file. Predictive performance was measured using c-statistics for binary outcomes (1-year and postoperative mortality, in-hospital complications) and root mean square prediction error (RMSE) for continuous outcomes (1-year all-cause medical costs, index hospitalization costs, length of stay [LOS]), after adjusting for age and sex. C-statistics were compared by the method of DeLong and colleagues (1988); RMSEs, by resampling. RESULTS: C-statistics were generally high (≥ ~ 0.8) for mortality but lower for in-hospital complications (~0.6-0.7). RMSEs for costs and hospitalization LOS were relatively large and comparable to standard deviations. Results were similar overall between the US and Canadian adaptations, with relative differences typically <1%. CONCLUSIONS: This US-based coding adaptation and a previously published Canadian adaptation resulted in similar predictive ability for all outcomes evaluated but may have different construct validity (not evaluated in our study). We recommend using adaptations specific to the country of data origin based on good research practice.

Clinical Characteristics, Treatments, and Concurrent Mutations in Non-Small Cell Lung Cancer Patients With NF1 Mutations.

OBJECTIVES: Metastatic non-small cell lung cancer (mNSCLC) is characterized by complex genomic alterations. NF1 mutations may confer distinct clinical characteristics within NSCLC, and real-world evidence on concurrent mutations, treatment patterns, and health outcomes is lacking. MATERIALS AND METHODS: This retrospective study was performed in patients with mNSCLC treated in the Flatiron Health network who underwent the FoundationOne tumor-sequencing. Anticancer therapies, concurrent mutations, real-world progression-free survival (rwPFS), and overall survival (OS) were assessed. RESULTS: Of the 1663 patients, 103 patients were identified with NF1 mutation. Concurrent mutations with Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (16.5%) and epidermal growth factor receptor fusion (6.8%) were the most frequent. In patients with NF1 mutation only (n = 57), 42% were women, 86% patients had smoking history, and 70% had non-squamous cell carcinoma type. Most (51%) of the patients with NF1 mutations received a single line of therapy versus other mutations and the overall treated population (44%). Platinum-based chemotherapy was the predominant first-line therapy, with programmed cell death-1/programmed cell death-ligand-1 inhibitors as subsequent lines of therapy. The NF1 mutation only group had numerically the shortest median rwPFS (82 days) than other mutation groups. Median OS for the NF1 mutation group in first, second, and third lines of therapy was 321, 498, and 210 days, respectively. CONCLUSIONS: NF1 mutations confer distinct clinical characteristics in patients with mNSCLC. These patients may have different trajectories for progression and survival than seen for other mutations, experience less systemic therapy after first-line therapy, and may have shorter survival.

Development and validation of coding algorithms to identify patients with incident lung cancer in United States healthcare claims data.

PURPOSE: Our aim was to develop and validate a practical US healthcare claims algorithm for identifying incident lung cancer that improves on positive predictive value (PPV) and sensitivity observed in past studies. METHODS: Patients newly diagnosed with lung cancer in Surveillance, Epidemiology, and End Results (SEER) (gold standard) were linked with Medicare claims. A 5% Medicare "other cancer" sample and noncancer sample served as controls. A split-sample validation approach was used. Rules-based, regression, and machine learning models for developing algorithms were explored. Algorithms were developed in the model building subset. Rules-based algorithms and those with the highest F scores were evaluated in the validation subset. F scores were compared for 1000 bootstrap samples. Misclassification was evaluated by calculating the odds of selection by the algorithm among true positives and true negatives. RESULTS: A practical single-score algorithm derived from a logistic regression model had sensitivity = 78.22% and PPV = 78.50% (F score: 78.36). The algorithm was most likely to misclassify older patients (ages ≥80 years) or with missing data in the SEER registry, shorter follow-up time in Medicare (<3 months), insurance through Veterans Affairs, >1 cancer in SEER, or certain Charlson comorbidities (dementia, chronic pulmonary disease, liver disease, or myocardial infarction). CONCLUSION: In this dataset, a practical point-based algorithm for identifying incident lung cancer demonstrated significant and substantial improvement (7.9% and 23.9% absolute improvement in sensitivity and PPV, respectively) compared with a current standard.

Real-World Outcomes and Factors Associated With the Second-Line Treatment of Patients With Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma.

This retrospective observational study was designed to evaluate overall survival in a real-world patient population and to identify predictive factors associated with receipt of second-line therapy. A retrospective analysis of electronic medical records (Flatiron Health, New York) was conducted among patients initiating first-line therapy from January 1, 2013, through April 30, 2018. Eligible patients were diagnosed with advanced gastric, gastroesophageal junction, or esophageal adenocarcinoma and ≥18 years of age at the time of treatment initiation. Patients alive 45 days after discontinuation of first-line therapy were considered potentially eligible for continued therapy and were categorized into those who received and those who did not receive second-line therapy. Survival analyses were conducted using Kaplan-Meier method and log-rank test without adjusting for any baseline covariates. Factors associated with further treatment were evaluated using logistic regression. A total of 3850 patients met eligibility criteria. Among the 2516 patients available to receive second-line therapy, 1515 (60.2%) received second-line therapy and 1001 (39.8%) did not receive further therapy. Among those potentially eligible to receive second-line therapy, median survival was 15.4 months (95% confidence interval [CI]: 14.6-16.0) from initiation of first-line therapy for those who received second-line therapy and 10.0 months (95% CI: 9.3-10.7) for those who did not. Longer duration of first-line therapy (≥169 vs ≤84 days), HER2-positive tumors, initially diagnosed with stage IV disease, less weight loss during first-line therapy, and younger age were associated with receipt of second-line therapy (all P < .001). Longer survival was associated with multiple lines of therapy; however, these results should be interpreted with caution, and no causal relationship can be inferred.

Sequential therapy with ramucirumab and/or checkpoint inhibitors for non-small-cell lung cancer in routine practice.

Aim: To describe treatment patterns and outcomes for advanced/metastatic non-small-cell lung cancer (aNSCLC) treated with single-agent or combination ramucirumab (ramucirumab-based) and/or immune checkpoint inhibitor (ICI-based) therapy. Materials & methods: Retrospective study of aNSCLC patients (n = 4054) identified in the Flatiron Health database, who received at least two treatment lines including ramucirumab- and/or ICI-based regimens between December 2014 and May 2017. Results: Median overall survival (95% CI) from aNSCLC diagnosis was 29.3 (25.5-33.0) months for patients receiving sequential ramucirumab- and ICI-based therapy (n = 245), 15.1 (12.6-18.2) months for patients receiving sequences including ramucirumab- without ICI-based therapy (n = 112), and 23.1 (21.9-24.2) months for patients receiving ICI-based therapy without ramucirumab-based therapy in sequence (n = 3697). Conclusion: Results provide real-world survival estimates for aNSCLC treated with sequences including ramucirumab- and/or ICI-based therapies.

Minimization of olaratumab drug waste using real-world data.

PURPOSE: Results of a study in which population-based body weight and body surface area (BSA) data were used for vial size optimization to reduce drug waste associated with administration of the i.v. anticancer agent olaratumab are reported. METHODS: A retrospective observational study was conducted to determine weight and BSA distributions in a large sample of U.S. oncology patients using data from a large electronic medical record database. Body weight and BSA values at the time of initial systemic anticancer therapy were used to compute olaratumab dose requirements in a cohort of patients with soft tissue sarcoma; those data were analyzed to derive estimates of drug waste likely to result from the use of various proposed olaratumab vial sizes in combination with an existing 500-mg size. Weight and BSA distributions were calculated for additional cohorts of patients with 7 other cancer types. RESULTS: Median weight values in men (n = 1,179) and women (n = 1,078) with soft tissue sarcoma were 82.55 kg (interquartile range [IQR], 72.58-95.53 kg) and 68.69 kg (IQR, 58.51-84.28 kg), respectively. Modeling of olaratumab dosing scenarios indicated that use of the 500-mg vial only would result in estimated average drug waste of 234 mg per patient per administration; analysis of various potential vial size combinations showed that waste could be reduced by 87.6% with the addition of a 190-mg vial size. CONCLUSION: Analysis of real-world patient weight and BSA data allowed olaratumab vial size optimization to enable maximal dosing flexibility with minimal drug waste.

Chemotherapy treatment patterns, costs, and outcomes of patients with gastric cancer in the United States: a retrospective analysis of electronic medical record (EMR) and administrative claims data.

BACKGROUND: The aim of this study was to conduct a retrospective database analysis to describe the chemotherapy treatment patterns and outcomes of patients with gastric cancer. METHODS: Individuals diagnosed with gastric cancer were identified from the IMS Oncology Database, which contains electronic medical record (EMR) data collected from a variety of community practices, and the Truven Health MarketScan(®) Research database, an administrative claims database. Eligible patients were 18 years of age or older and had an ICD-9 code 151.0-151.9. Patients were excluded if they had evidence of cancer within 6 months of the index diagnosis. RESULTS: There were 5257 eligible patients identified in EMR data: 1982 (37.7 %) of these patients also had data regarding chemotherapy treatments. Of the 1982 patients who received first-line therapy, 42.3 %, 18.1 %, and 7.9 % went on to receive a second, third, and fourth line of chemotherapy, respectively. There were 11891 eligible patients identified in the administrative database; 5299 (44.6 %) had data regarding chemotherapy. Of those initiating chemotherapy, 2888 (54.5 %) received a second line and 1598 (30.2 %) received a third line of treatment. The average total cost of care during first-line therapy was $40,811 [standard deviation (SD) = $49,916], which was incurred over an average of 53.5 (SD = 63.4) days. A similar pattern was evident in second-line treatment (mean/SD, $26,588/$33,301) over 41.2 (SD = 55.7) days. CONCLUSIONS: Costs and duration of care received vary among gastric cancer patients in the U.S. There is a need to understand which regimens may be associated with better health outcomes and to standardize treatment as appropriate.

Safety, resource use, and quality of life in paramount: a phase III study of maintenance pemetrexed versus placebo after induction pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer.

INTRODUCTION: In a phase III, randomized, double-blind study (PARAMOUNT), maintenance pemetrexed demonstrated significant benefit in advanced non-small-cell lung cancer (NSCLC). We present safety, resource use, and quality of life (QoL) results. METHODS: After four 21-day cycles of pemetrexed-cisplatin (N = 939), patients with advanced nonsquamous NSCLC, whose disease had not progressed and who had a performance status of 0/1, were randomized 2:1 (N = 539) to maintenance pemetrexed 500 mg/m plus best supportive care or placebo plus best supportive care every 21 days until disease progression or unacceptable toxicity. QoL was measured using the EuroQol 5-dimensional questionnaire (EQ-5D). RESULTS: Frequently reported grade 3 to 4 drug-related toxicities with maintenance pemetrexed versus placebo were anemia (4.5% versus 0.6%; p = 0.016), fatigue (4.2% versus 0.6%; p = 0.016), and neutropenia (3.6% versus 0.0%; p < 0.006). No significant differences in drug-related grade 3 to 5 toxicities were observed with long-term pemetrexed exposure (>6 cycles), except grade 3 to 4 neutropenia, which did not result in increased infections. Patients on maintenance pemetrexed required more transfusions (13.4% versus 5.0%; p = 0.003), granulocyte colony- or granulocyte-macrophage colony-stimulating factors (5.3% versus 0.0%; p <0.001), anti-infectives (25.3% versus 16.7%; p = 0.028), and hospitalizations because of study drug (8.4% versus 3.3%, p = 0.028) than placebo-treated patients did. No significant treatment-by-time interactions, overall treatment differences, or clinically relevant changes from baseline were observed in EQ-5D scores during treatment. CONCLUSIONS: Long-term use of continuation maintenance pemetrexed was well tolerated; resource use was low, corresponding with known pemetrexed toxicities. The EQ-5D results demonstrate that patients tolerate long-term maintenance pemetrexed without worsening QoL.

Duloxetine versus placebo for the treatment of women with stress predominant urinary incontinence in Taiwan: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: This manuscript compares the efficacy and safety of duloxetine with placebo in Taiwanese women with SUI. METHODS: Taiwanese women with SUI were were randomly assigned to placebo (n = 61) or duloxetine 80 mg/day (n = 60) in this double-blind, 8-week, placebo-controlled study. Outcome variables included: incontinence episode frequency (IEF), Incontinence Quality of Life questionnaire (I-QOL) scores, and Patient Global Impression of Improvement rating (PGI-I). RESULTS: Decrease in IEF was significantly greater in duloxetine-treated than placebo-treated women (69.98% vs 42.56%, P < .001). No treatment differences in I-QOL scores were significant. There were significant differences in PGI-I rating. Treatment-emergent adverse events (TEAEs) were experienced by more duloxetine-treated than placebo-treated women (80.0% vs 44.3%; P < .001). Discontinuations due to adverse events were significantly greater for duloxetine-treated than placebo-treated women (26.7% vs 6.6%; P = .003). CONCLUSION: Data provide evidence for the safety and efficacy of duloxetine for the treatment for Taiwanese women with SUI. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00475358.