TURALIO® Risk Evaluation and Mitigation Strategy Program (tREMS): 3-year retrospective hepatic safety assessment.

Aim: Hepatic safety data assessment from the TURALIO® (pexidartinib) Risk Evaluation and Mitigation Strategy (tREMS) Program. Methods: Retrospective 3-year assessment (August 2019 to June 2022) of hepatic events from the TURALIO® (pexidartinib) Risk Evaluation and Mitigation Strategy Program. Results: A total of 451 patients, 369 prescribers, 2 wholesalers/distributors and 2 pharmacies were enrolled and certified. Twenty-one (4.7%) patients met the criteria for a hepatic adverse event or laboratory abnormality suggestive of serious and potentially fatal liver injury, all with onset within 2 months of therapy. No new hepatic safety signals were identified. Conclusion: Results are consistent with the phase 3 ENLIVEN trial data. Liver enzyme monitoring, combined with early intervention, including dose modification and discontinuation, conducted in patients treated with pexidartinib mitigate the risk of potential hepatotoxicity.

Safety findings from the 3-year data collected in the TURALIO^® Risk Evaluation and Mitigation Strategy ProgramPexidartinib (TURALIO^®) is an oral drug that is used to treat adults with tenosynovial giant cell tumor (TGCT) that cannot be fixed with surgery. TGCTs are rare, noncancerous tumors that cause pain, stiffness and difficulty moving. Pexidartinib works by blocking a protein that helps these tumors grow. Before pexidartinib, there were no good treatments for TGCT and surgery often could not remove all the tumors, so they would frequently grow back.Pexidartinib was approved in 2019 after a clinical trial showed it worked well in adults with TGCT. However, pexidartinib can sometimes cause serious liver harm for some patients. To handle this risk, a program called the tREMS (TURALIO^® Risk Evaluation and Mitigation Strategy) was established to ensure that pexidartinib is used safely.The tREMS Program teaches doctors, pharmacists and patients about the safe use of pexidartinib and potential liver risks and enrolls patients in a registry to watch their health. Doctors and pharmacies must be certified, and patients need regular liver tests. In the first 3 years, 451 patients and 369 doctors joined the program. Unintended liver issues were found in around 5% of patients, a rate that is about the same as that seen in pexidartinib clinical trials, and no new safety concerns were found. About half of patients with liver issues could reverse them by stopping pexidartinib. No patient had permanent liver damage, needed a transplant or died from liver problems. These results show that the tREMS Program is working well to keep patients with TGCT safe while taking pexidartinib.

Real-world drug utilization and treatment patterns in patients with tenosynovial giant cell tumors in the USA.

Aim: Real-world treatment patterns in tenosynovial giant cell tumor (TGCT) patients remain unknown. Pexidartinib is the only US FDA-approved treatment for TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery. Objective: To characterize drug utilization and treatment patterns in TGCT patients. Methods: In a retrospective observational study using IQVIA's linked prescription and medical claims databases (2018-2021), TGCT patients were stratified by their earliest systemic therapy claim (pexidartinib [N = 82] or non-FDA-approved systemic therapy [N = 263]). Results: TGCT patients treated with pexidartinib versus non-FDA-approved systemic therapies were predominantly female (61 vs 50.6%) and their median age was 47 and 54 years, respectively. Pexidartinib-treated patients had the highest 12-month probability of remaining on treatment (54%); 34.1% of pexidartinib users had dose reduction after their first claim. Conclusion: This study provides new insights into the unmet need, utilization and treatment patterns of systemic therapies for the treatment of TGCT patients.

Treatment patterns in patients with tenosynovial giant cell tumors in the USAThis database study is the first investigation of how drugs are used to treat patients with tenosynovial giant cell tumor (TGCT) in the real world. We researched adult TGCT patients from IQVIA's prescription and medical claims databases who started treatment with pexidartinib (N = 82) or other non-US FDA-approved systemic therapies (N = 263). The patients included in this analysis were mostly women (61.0 and 50.6%) and their median age was 47 and 54 years for pexidartinib and other non-FDA-approved systemic therapies, respectively. The patients treated with pexidartinib were most likely to remain on treatment (54.0%) at the end of the first year. Most patients (79.3%) started pexidartinib treatment at a total daily dose of 800 mg/day, as per the product label. Only 34.1% of patients had reduced medication dose during follow-up. Of note, this study found that TGCT patients were treated with other systemic therapies which remain unproven to be safe and effective in medical studies of TGCT. Given the unmet need, and with pexidartinib being the only approved systemic treatment in USA, there is an opportunity for the larger population of adult TGCT patients to benefit from its use. Further research is needed to identify barriers for access to pexidartinib and treatment of TGCT patients.

Real-world treatment patterns, healthcare resource utilization and costs among patients with peripheral T-cell lymphoma.

Objective: To evaluate treatment patterns, healthcare resource utilization (HRU) and costs among peripheral T-cell lymphoma (PTCL) patients in the USA. Methods: A retrospective cohort study, using the IQVIA PharMetrics® Plus claims database from 1 April 2011 to 30 November 2021, identified PTCL patients receiving systemic treatments. Three mutually exclusive subcohorts were created based on line of therapy (LOT): 1LOT, 2LOT and ≥3LOT. Common treatment regimens, median time on treatment, all-cause and PTCL-related HRU and costs were estimated. Results: Among 189 PTCL patients identified, 61.9% had 1LOT, 21.7% had 2LOT and 16.4% had ≥3LOT. The most common treatment regimens in the 1LOT were CHOP/CHOP-like, CHOEP/CHOEP-like and brentuximab vedotin; monotherapies were most common in the 2LOT and ≥3LOT. All-cause and PTCL-related hospitalizations and prescriptions PPPM increased with increasing LOT. Nearly 70% of total treatment costs were PTCL related. Conclusion: Higher utilization of combination therapies in the 1LOT and monotherapies in subsequent LOTs were observed, alongside high PTCL-related costs.

Peripheral T-cell lymphomas (PTCL) are a rare and fast-growing form of blood cancer. About 8000­12,000 people in the USA are diagnosed with PTCL every year. As it is a rare disease and has many types, and there is a limited understanding of the patients who have PTCL and the treatments they receive in the real world. The purpose of this study was to evaluate how these patients are treated, what are they treated with and what are the costs of these treatments in the USA. The data collected on these patients was divided into three groups based upon the number of lines of treatment/therapy (LOT) they received: 1LOT, 2LOT and ≥3LOT. This study researched different treatments and their duration in each line of therapy. Among 189 PTCL patients included in the study, the average age of patients was 55 years and 62% were male. Among these patients, 62% had 1LOT, 22% had 2LOT and 16% had ≥3LOT. The most common treatments in the 1LOT were traditional chemotherapy regimens followed by targeted therapies: CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or CHOP-like, CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide and prednisone) or CHOEP-like, and brentuximab vedotin. Treatment regimens with only one drug were most common in the 2LOT and ≥3LOT. The total cost of PTCL treatment in the USA is very high; 70% of this cost is related to their treatment with various drugs. More research is needed to better understand the treatment and cost of this rare cancer.

Characteristics and outcomes of elderly patients with acute myeloid leukemia who receive no treatment in the Surveillance, Epidemiology and End Results-Medicare database.

Background: Without treatment, acute myeloid leukemia (AML) is rapidly fatal. Nevertheless, a large proportion of elderly AML patients do not receive any treatment. Aim: To characterize the demographics, comorbidities, survival and prognostic factors of elderly AML patients who do not receive any AML treatment or supportive care (SC). Methods: A retrospective cohort analysis of the Surveillance, Epidemiology and End Results-Medicare database (2008-2015). Results: Of 7665 AML patients, 2373 (31%) did not receive any AML treatment or SC. The mean age was 80.4 years, 52.8% were males and 79.7% and 95.3% died within the first 60 and 180 days, respectively; 2.1% survived >12 months and only 5.5% of patients had remission or relapse codes populated. Conclusion: Older age, male gender, concurrent depression, ischemic heart disease, chronic kidney disease and benign prostatic hyperplasia were associated with a decreased likelihood of survival. Multiple factors contribute to the complex clinical status of these patients preventing intensive chemotherapy; they should still ideally be treated, at least with the best SC.

An analysis of the data collected in the Surveillance, Epidemiology and End Results-Medicare database from 2008 to 2015 was performed. This database includes data collected by a national cancer registry on people diagnosed with cancer in the United States and those who enroll in Medicare. This study focused on acute myeloid leukemia (AML) patients who did not receive any AML treatment or supportive care (SC). Of 7665 patients with AML, 2373 (31%) did not receive any AML treatment or SC. At the time the data was indexed for each patient in the database, their mean age was 80.4 years and around 53% were males. Within the first 60 days, around 80% of these patients died; over 95% died within the first 180 days. Only 2% of patients survived more than a year without treatment; these patients were likely in remission. Without treatment, AML patients who were older, were male or who also had depression, ischemic heart disease, chronic kidney disease or benign prostatic hyperplasia had a higher chance of dying early. There could be many reasons why these patients are not treated. The main reasons are their poor health condition and the presence of two or more health conditions in a patient at the same time (comorbidities). However, they should still ideally be treated, at least with the best SC. Additional treatment options are urgently needed for elderly AML patients who have comorbidities and are in poor general health.

Elderly patients with acute myeloid leukemia who only receive supportive care in the Surveillance, Epidemiology and End Results-Medicare database: demographics, treatment patterns and outcomes.

Aim: Elderly acute myeloid leukemia (AML) patients are often not treated with antileukemic therapy due to their poor overall health condition, leaving supportive care as the sole treatment option. Objective: To evaluate patient characteristics, treatment patterns and outcomes of elderly patients with AML who are treated with supportive care only. Methods: A retrospective analysis of elderly AML patients included in the Surveillance, Epidemiology and End Results-Medicare database from 2008 to 2015. Results: Of elderly patients with AML (n = 7665), 3209 (41.9%) received supportive care only. Their mean age was 79 years, 50.5% were males; 48.2% died during the first 3 months and 67.3% died during the first 6 months. 82.2% died within the first year; only 13.2% survived >12 months. 77.9% patients died due to leukemia. Conclusion: In elderly AML patients treated with supportive care only, older age, concurrent hypertension, chronic obstructive pulmonary disease, chronic kidney disease and acute myocardial infarction were identified as prognostic factors associated with decreased likelihood of survival. Ideally, these patients should be treated with antileukemic therapy in addition to supportive care, as most of them die from disease progression.

This study analyzed data on elderly patients with acute myeloid leukemia (AML) who were only treated with supportive care. The source of this data was the Surveillance, Epidemiology and End Results (SEER)-Medicare database. Of the 7665 patients diagnosed with AML during 2008­2015, 3209 (41.9%) received supportive care only. Their mean age at index date was 79 years; slightly more than half of these were males (50.5%). Almost half of these patients (48.2%) died within the first 3 months and approximately two-thirds (67.3%) died within the first 6 months. Only a small proportion (13%) of these patients were alive after 1 year. These patients who were alive after one were likely to be in remission (there was decrease in the signs and symptoms of AML). The results of this study showed that elderly AML patients who only received supportive care were more likely to die early if they also had chronic kidney disease, chronic obstructive pulmonary disease, history of acute myocardial infarction or hypertension. As elderly AML patients may be in poor general health and have other diseases (comorbidities), this could be the reason why they may not be treated with antileukemic therapy. Instead of treatment with supportive care only, these patients should ideally receive antileukemic therapy in addition to supportive care. More research should be done to find alternate treatments for these elderly AML patients.

Health-related quality of life in women with breast cancer: a review of measures.

BACKGROUND: To identify and describe the breast cancer-specific health-related quality of life (HRQoL) instruments with evidence of validation in the breast cancer population for potential use in patients treated for breast cancer (excluding surgery). METHODS: We conducted a systematic literature review using PubMed, Embase, and PsycINFO databases to identify articles that contain psychometric properties of HRQoL instruments used in patients with breast cancer. Relevant literature from January 1, 2009, to August 19, 2019, was searched. Articles published in English that reported psychometric properties (reliability, validity) of HRQoL instruments were identified. RESULTS: The database search yielded 613 unique records; 131 full-text articles were reviewed; 80 articles presented psychometric data for instruments used in breast cancer (including generic measures). This article reviews the 33 full articles describing psychometric properties of breast cancer-specific HRQoL instruments: EORTC QLQ-C30, EORTC QLQ-BR23, FACT-B, FBSI, NFBSI-16, YW-BCI36, BCSS, QuEST-Br, QLICP-BR, INA-BCHRQoL, and two newly developed unnamed measures, one by Deshpande and colleagues (for use in India) and one by Vanlemmens and colleagues (for use among young women and their partners). The articles that described the EORTC QLQ-C30, QLQ-BR23, and FACT-B centered on validating translations, providing additional support for content validity, and demonstrating acceptability of electronic patient-reported outcome administration. Psychometric properties of the measures were acceptable. Several new measures have been developed in Asia with an emphasis on development on cultural relevance/sensitivity. Others focused on specific populations (i.e., young women with breast cancer). CONCLUSIONS: Historically, there have been limited options for validated measures to assess HRQoL of patients with breast cancer. A number of new measures have been developed and validated, offering promising options for assessing HRQoL in this patient population. This review supports the reliability and validity of the EORTC QLQ-C30 and FACT-B; new translations and electronic versions of these measures further support their use for this population.

Turalio risk evaluation and mitigation strategy for treatment of tenosynovial giant cell tumor: framework and experience.

For drugs with enhanced serious safety risks, Risk Evaluation and Mitigation Strategy (REMS) may be required. Pexidartinib is approved for treatment of adult symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery. Its approval was conditional on its prescription via a mandatory REMS due to serious and potentially fatal liver injury seen in clinical trials. Turalio® REMS aims to mitigate this risk by ensuring provider education on pexidartinib use and required REMS components, prescriber adherence to baseline and periodic monitoring, and enrolling patients in a registry to further assess safe use and acute, chronic and irreversible hepatotoxicity. Through Turalio REMS, benefits of treating patients with pexidartinib may be preserved.

For drugs with serious side effects, specific safety measures may be put in place to manage these serious side effects in the form of Risk Evaluation and Mitigation Strategy (REMS) programs. Pexidartinib (Turalio^®) is approved for treatment of adults who have symptoms of severe tenosynovial giant cell tumor or have limitations in function that do not improve with surgery. Turalio^® has an REMS program because liver injuries that can be serious or fatal were seen in Pexidartinib clinical trials. This program aims to decrease the seriousness of the liver injuries by assuring doctors and pharmacists are educated on how to use the drug, patients are advised of this potential risk and that baseline and periodic monitoring of patients are conducted.

Data sources for drug utilization research in Latin American countries-A cross-national study: DASDUR-LATAM study.

PURPOSE: Drug utilization research (DUR) contributes to inform policymaking and to strengthen health systems. The availability of data sources is the first step for conducting DUR. However, documents that systematize these data sources in Latin American (LatAm) countries are not known. We compiled the potential data sources for DUR in the LatAm region. METHODS: A network of DUR experts from nine LatAm countries was assembled and experts conducted: (i) a website search of the government, academic, and private health institutions; (ii) screening of eligible data sources, and (iii) liaising with national experts in pharmacoepidemiology (via an online survey). The data sources were characterized by accessibility, geographic granularity, setting, sector of the data, sources and type of the data. Descriptive analyses were performed. RESULTS: We identified 125 data sources for DUR in nine LatAm countries. Thirty-eight (30%) of them were publicly and conveniently available; 89 (71%) were accessible with limitations, and 18 (14%) were not accessible or lacked clear rules for data access. From the 125 data sources, 76 (61%) were from the public sector only; 46 (37%) were from pharmacy records; 43 (34%) came from ambulatory settings and; 85 (68%) gave access to individual patient-level data. CONCLUSIONS: Although multiple sources for DUR are available in LatAm countries, the accessibility is a major challenge. The procedures for accessing DUR data should be transparent, feasible, affordable, and protocol-driven. This inventory could permit a comparison of drug utilization between countries identifying potential medication-related problems that need further exploration.

Prognostic factors of brain metastasis and survival among HER2-positive metastatic breast cancer patients: a systematic literature review.

BACKGROUND: Patients with breast cancer who overexpress the human epidermal growth factor receptor 2 (HER2) and subsequently develop brain metastasis (BM) typically experience poor quality of life and low survival. We conducted a comprehensive literature review to identify prognostic factors for BM and predictors of survival after developing BM, and the effects of therapies with different mechanisms of action among patients with HER2+ breast cancer (BC). METHODS: A prespecified search strategy was used to identify research studies investigating BM in patients with HER2+ BC published in English during January 1, 2009-to June 25, 2021. Articles were screened using a two-phase process, and data from selected articles were extracted. RESULTS: We identified 25 published articles including 4097 patients with HER2+ BC and BM. Prognostic factors associated with shorter time to BM diagnosis after initial BC diagnosis included younger age, hormone receptor negative status, larger tumor size or higher tumor grade, and lack of treatment with anti-HER2 therapy. Factors predictive of longer survival after BM included having fewer brain lesions (< 3 or a single lesion) and receipt of any treatment after BM, including radiosurgery, neurosurgery and/or systemic therapy. Patients receiving combination trastuzumab and lapatinib therapy or trastuzumab and pertuzumab therapy had the longest median survival compared with other therapies assessed in this review. CONCLUSIONS: More research is needed to better understand risk factors for BM and survival after BM in the context of HER2+ BC, as well as the assessment of new anti-HER2 therapy regimens that may provide additional therapeutic options for BM in these patients.

Challenges facing drug utilization research in the Latin American region.

PURPOSE: The International Society of Pharmacoepidemiology (ISPE) in collaboration with the Latin America Drug Utilization Research Group (LatAm DURG), the Medicines Utilization Research in Africa (MURIA) group, and the Uppsala Monitoring Center, is leading an initiative to understand challenges to drug utilization research (DUR) in the Latin American (LatAm) and African regions with the goal of communicating results and proposing solutions to these challenges in four scientific publications. The purpose of this first manuscript is to identify the main challenges associated with DUR in the LatAm region. METHODS: Drug utilization (DU) researchers in the LatAm region voluntarily participated in multiple discussions, contributed with local data and reviewed successive drafts and the final manuscript. Additionally, we carried out a literature review to identify the most relevant publications related to DU studies from the LatAm region. RESULTS: Multiple challenges were identified in the LatAm region for DUR including socioeconomic inequality, access to medical care, complexity of the healthcare system, limited investment in research and development, limited institutional and organization resources, language barriers, limited health education and literacy. Further, there is limited use of local DUR data by decision makers particularly in the identification of emerging health needs coming from social and demographic transitions. CONCLUSIONS: The LatAm region faces challenges to DUR which are inherent in the healthcare and political systems, and potential solutions should target changes to the system.

Frequency of Early Refills for Opioids in the United States.

OBJECTIVE: Refilling an opioid prescription early is an important risk factor of prescription opioid abuse and misuse; we aimed to understand the scope of this behavior. This study was conducted to quantify the prevalence and distribution of early refills among patients prescribed opioids. METHODS: We conducted a retrospective cohort study utilizing dispensed prescription records. Patients filling one or more prescription opioids were identified and followed for one year. Early refills were defined as having a second prescription filled ≥15% early relative to the days' supply of the previous prescription for the same opioid (according to the National Drug Code [NDC]). The distribution of the number of early refills and patient characteristics were assessed. RESULTS: A total of 60.6 million patients met the study criteria; 28.8% had two or more opioid prescriptions for the same opioid during follow-up. Less than 3% of all patients receiving an opioid had an early refill. Approximately 10% of those with two or more opioid prescriptions for the same drug had an early refill. For patients with multiple fills (N = 1.5 million with extended-release long-acting [ER/LA] opioids; N = 17.1 million with immediate-release short-acting [IR/SA] opioids), early refills were more common among patients with an ER/LA opioid (18.5%) compared with an IR/SA opioid (8.7%). Three-quarters of patients with an early refill had only one (70.9% and 78.4% for ER/LA and IR/SA, respectively). CONCLUSION: Refilling an opioid prescription with the same opioid early is an infrequent behavior within all opioid users, but more common in ER/LA users. Patients who refilled early tended to do so just once.

Potential biomarkers in breast cancer drug development: application of the biomarker qualification evidentiary framework.

Breast cancer treatments have evolved rapidly, and clinically meaningful biomarkers have been used to guide therapy. These biomarkers hold utility within the drug development process to increase the efficiency and effectiveness. To this purpose, the US FDA developed an evidentiary framework. Literature searches conducted of literature published between 2016 and 2022 identified biomarkers in breast cancer. These biomarkers were reviewed for drug development utility through the biomarker qualification evidentiary framework. In the breast cancer setting, several promising biomarkers (ctDNA, Ki-67 and PIK3CA) were identified. There is a need for increased transparency regarding the requirements for qualification of specific biomarkers and increased awareness of the processes involved in biomarker qualification.

[Box: see text].

Clinical Management of Patients with Non-Small Cell Lung Cancer, Brain Metastases, and Actionable Genomic Alterations: A Systematic Literature Review.

INTRODUCTION: Nearly 60% of patients with non-small cell lung cancer (NSCLC) present with metastatic disease, and approximately 20% have brain metastases (BrMs) at diagnosis. During the disease course, 25-50% of patients will develop BrMs. Despite available treatments, survival rates for patients with NSCLC and BrMs remain low, and their overall prognosis is poor. Even with newer agents for NSCLC, options for treating BrMs can be limited by their ineffective transport across the blood-brain barrier (BBB) and the unique brain tumor microenvironment. The presence of actionable genomic alterations (AGAs) is a key determinant of optimal treatment selection, which aims to maximize responses and minimize toxicities. The objective of this systematic literature review (SLR) was to understand the current landscape of the clinical management of patients with NSCLC and BrMs, particularly those with AGAs. METHOD: A Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-compliant SLR was conducted to identify studies in patients with BrMs in NSCLC. Searches used the EMBASE and MEDLINE® databases, and articles published between January 1, 2017 and September 26, 2022 were reviewed. RESULTS: Overall, 179 studies were included in the SLR. This subset review focused on 80 studies that included patients with NSCLC, BrMs, and AGAs (19 randomized controlled trials [RCTs], two single-arm studies, and 59 observational studies). Sixty-four of the 80 studies reported on epidermal growth factor receptor (EGFR) mutations, 14 on anaplastic lymphoma kinase (ALK) alterations, and two on both alterations. Ninety-five percent of studies evaluated targeted therapy. All RCTs allowed patients with previously treated, asymptomatic, or neurologically stable BrMs; the percentage of asymptomatic BrMs varied across observational studies. CONCLUSIONS: Although targeted therapies demonstrate systemic benefits for patients with NSCLC, BrMs, and AGAs, there remains a continued need for effective therapies to treat and prevent BrMs in this population. Increased BBB permeability of emerging therapies may improve outcomes for this population.

Real-World Treatment Patterns and Clinical Outcomes Among Patients with Metastatic or Unresectable EGFR-Mutated Non-Small Cell Lung Cancer Previously Treated with Osimertinib and Platinum-Based Chemotherapy.

INTRODUCTION: For patients with epidermal growth factor receptor-mutated (EGFRm) locally advanced/metastatic non-small cell lung cancer (mNSCLC) whose disease has progressed on or after osimertinib and platinum-based chemotherapy (PBC), no uniformly accepted standard of care exists. Moreover, limited efficacy of standard treatments indicates an unmet medical need, which is being addressed by ongoing clinical investigations, including the HERTHENA-Lung01 (NCT04619004) study of patritumab deruxtecan (HER3­DXd). However, because limited information is available on real-world clinical outcomes in such patients, early-phase trials of investigational therapies lack sufficient context for comparison. This study describes the real-world clinical characteristics, treatments, and outcomes for patients with EGFRm mNSCLC who initiated a new line of therapy following previous osimertinib and PBC, including a subset matched to the HERTHENA-Lung01 population. METHODS: This retrospective analysis used a US database derived from deidentified electronic health records. The reference cohort included patients with EGFRm mNSCLC who had initiated a new line of therapy between November 13, 2015 and June 30, 2021, following prior osimertinib and PBC. A subset of patients resembling the HERTHENA-Lung01 population was then extracted from the reference cohort; this matched subset was optimized using propensity score (PS) weighting. Endpoints were real-world overall survival (rwOS) and real-world progression-free survival (rwPFS). Confirmed real-world objective response rate (rwORR; partial/complete response confirmed ≥ 28 days later) was calculated for the response-evaluable subgroups of patients (with ≥ 2 response assessments spaced ≥ 28 days apart). RESULTS: In the reference cohort (N = 273), multiple treatment regimens were used, and none was predominant. Median rwPFS and rwOS were 3.3 and 8.6 months, respectively; confirmed rwORR (response evaluable, n = 123) was 13.0%. In the matched subset (n = 126), after PS weighting, median rwPFS and rwOS were 4.2 and 9.1 months, respectively; confirmed rwORR (response evaluable, n = 57) was 14.1%. CONCLUSION: The treatment landscape for this heavily pretreated population of patients with EGFRm mNSCLC is fragmented, with no uniformly accepted standard of care. A high unmet need exists for therapeutic options that provide meaningful improvements in clinical benefit.

Impact of interventions on medication adherence and blood pressure control in patients with essential hypertension: a systematic review by the ISPOR medication adherence and persistence special interest group.

OBJECTIVES: To systematically review the evidence on the impact of interventions to improve medication adherence in adults prescribed antihypertensive medications. METHODS: An electronic search was undertaken of articles published between 1979 and 2009, without language restriction, that focused on interventions to improve antihypertensive medication adherence among patients (≥18 years) with essential hypertension. Studies must have measured adherence as an outcome of the intervention. We followed standard guidelines for the conduct and reporting of the review and conducted a narrative synthesis of reported data. RESULTS: Ninety-seven articles were identified for inclusion; 35 (35 of 97, 36.1%) examined interventions to directly improve medication adherence, and the majority (58 of 97, 59.8%) were randomized controlled trials. Thirty-four (34 of 97, 35.1%) studies reported a statistically significant improvement in medication adherence. DISCUSSION/CONCLUSIONS: Interventions aimed at improving patients' knowledge of medications possess the greatest potential clinical value in improving adherence with antihypertensive therapy. However, we identified several limitations of these studies, and advise future researchers to focus on using validated adherence measures, well-designed randomized controlled trials with relevant adherence and clinical outcomes, and guidelines on the appropriate design and analysis of adherence research.

Discrepancies in ICD-9/ICD-10-based codes used to identify three common diseases in cancer patients in real-world settings and their implications for disease classification in breast cancer patients and patients without cancer: a literature review and descriptive study.

Background: International Classification of Diseases, Ninth/Tenth revisions, clinical modification (ICD-9-CM, ICD-10-CM) are frequently used in the U.S. by health insurers and disease registries, and are often recorded in electronic medical records. Due to their widespread use, ICD-based codes are a valuable source of data for epidemiology studies, but there are challenges related to their accuracy and reliability. This study aims to 1) identify ICD-9/ICD-10-based codes reported in literature/web sources to identify three common diseases in elderly patients with cancer (anemia, hypertension, arthritis), 2) compare codes identified in the literature/web search to SEER-Medicare's 27 CCW Chronic Conditions Algorithm ("gold-standard") to determine their discordance, and 3) determine sensitivity of the literature/web search codes compared to the gold standard. Methods: A literature search was performed (Embase, Medline) to find sources reporting ICD codes for at least one disease of interest. Articles were screened in two levels (title/abstract; full text). Analysis was performed in SAS Version 9.4. Results: Of 106 references identified, 29 were included that reported 884 codes (155 anemia, 80 hypertension, 649 arthritis). Overall discordance between the gold standard and literature/web search code list was 32.9% (22.2% for ICD-9; 35.7% for ICD-10). The gold standard contained codes not found in literature/web sources, including codes for hypertensive retinopathy/encephalopathy, Page Kidney, spondylosis/spondylitis, juvenile arthritis, thalassemia, sickle cell disorder, autoimmune anemias, and erythroblastopenia. Among a cohort of non-cancer patients (N=684,376), the gold standard identified an additional 129 patients with anemia, 33,683 with arthritis, and 510 with hypertension compared to the literature/web search. Among a cohort of breast cancer patients (N=303,103), the gold standard identified an additional 59 patients with anemia, 10,993 with arthritis, and 163 with hypertension. Sensitivity of the literature/web search code list was 91.38-99.96% for non-cancer patients, and 93.01-99.96% for breast cancer patients. Conclusion: Discrepancies in codes used to identify three common diseases resulted in variable differences in disease classification. In all cases, the gold standard captured patients missed using the literature/web search codes. Researchers should use standardized, validated coding algorithms when available to increase consistency in research and reduce risk of misclassification, which can significantly alter the findings of a study.

The Use of Biomarkers in Pharmacovigilance: A Systematic Review of the Literature.

Background: The use of biomarkers varies from disease etiognosis and diagnosis to signal detection, risk prediction, and management. Biomarker use has expanded in recent years, however, there are limited reviews on the use of biomarkers in pharmacovigilance and specifically in the monitoring and management of adverse drug reactions (ADRs). Objective: The objective of this manuscript is to identify the multiple uses of biomarkers in pharmacovigilance irrespective of the therapeutic area. Design: This is a systematic review of the literature. Data Sources and Methods: Embase and MEDLINE database searches were conducted for literature published between 2010-March 19, 2021. Scientific articles that described the potential use of biomarkers in pharmacovigilance in sufficient detail were reviewed. Papers that did not fulfill the United States Food and Drug Administration (US FDA) definition of a biomarker were excluded, which is based on the International Conference on Harmonisation (ICH)-E16 guidance. Results: Twenty-seven articles were identified for evaluation. Most articles involved predictive biomarkers (41%), followed by safety biomarkers (38%), pharmacodynamic/response biomarkers (14%), and diagnostic biomarkers (7%). Some articles described biomarkers that applied to multiple categories. Conclusion: Various categories of biomarkers including safety, predictive, pharmacodynamic/response, and diagnostic biomarkers are being investigated for potential use in pharmacovigilance. The most frequent potential uses of biomarkers in pharmacovigilance in the literature were the prediction of the severity of an ADR, mortality, response, safety, and toxicity. The safety biomarkers identified were used to evaluate patient safety during dose escalation, identify patients who may benefit from further biomarker testing during treatment, and monitor ADRs.

Use of Real-World Evidence in a Virtual Bridging Analysis for a Human Epidermal Growth Factor Receptor 2-Targeted Antibody-Drug Conjugate in Gastric Cancer.

This study bridged pharmacokinetic, efficacy, and safety clinical trial data from Japan to a Western population using real-world evidence (RWE) to investigate the antibody-drug conjugate trastuzumab deruxtecan (T-DXd) in the treatment of human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer. Using population pharmacokinetic and exposure-response (efficacy/safety) models, exposure-efficacy data from 117 patients and exposure-safety data from 158 patients in Japan who received T-DXd 6.4 mg/kg as second-line or later treatment were bridged to RWE including covariate information from 25 Western patients with HER2-positive gastric cancer who received second-line or later T-DXd treatment. Pharmacokinetic simulations indicated that intact T-DXd and released drug (DXd) steady-state exposures were comparable between Western patients and patients from Japan; the Western/Japan ratio of exposure medians ranged from 0.82 (T-DXd steady-state minimum concentration) to 1.18 (DXd steady-state maximum concentration). Exposure-efficacy simulations estimated a confirmed objective response rate of 28.6% (90% confidence interval, 20.8-38.4) in real-world Western patients versus 40.1% (90% confidence interval, 33.5-47.0) in patients from Japan, possibly because of checkpoint inhibitor use in 4% versus 30% of patients, respectively. Western patients had a higher estimated rate of serious adverse events than patients from Japan (42.2% vs 34.6%); however, the rate of interstitial lung disease was lower (less than 10%) in Western patients. Overall, T-DXd was predicted to have meaningful clinical activity and a manageable safety profile in Western patients with HER2-positive gastric cancer. Using RWE, bridging analysis supported US approval of T-DXd 6.4 mg/kg in advanced gastric cancer before a clinical trial was completed in Western patients.

Incidence and Risk Factors for Development of Cardiac Toxicity in Adult Patients with Newly Diagnosed Acute Myeloid Leukemia.

The incidence of cardiac morbimortality in acute myeloid leukemia (AML) is not well known. We aim to estimate the cumulative incidence (CI) of cardiac events in AML patients and to identify risk factors for their occurrence. Among 571 newly diagnosed AML patients, 26 (4.6%) developed fatal cardiac events, and among 525 treated patients, 19 (3.6%) experienced fatal cardiac events (CI: 2% at 6 months; 6.7% at 9 years). Prior heart disease was associated with the development of fatal cardiac events (hazard ratio (HR) = 6.9). The CI of non-fatal cardiac events was 43.7% at 6 months and 56.9% at 9 years. Age ≥ 65 (HR = 2.2), relevant cardiac antecedents (HR = 1.4), and non-intensive chemotherapy (HR = 1.8) were associated with non-fatal cardiac events. The 9-year CI of grade 1-2 QTcF prolongation was 11.2%, grade 3 was 2.7%, and no patient had grade 4-5 events. The 9-year CI of grade 1-2 cardiac failure was 1.3%, grade 3-4 was 15%, and grade 5 was 2.1%; of grade 1-2, arrhythmia was 1.9%, grade 3-4 was 9.1%, and grade 5 was 1%. Among 285 intensive therapy patients, median overall survival decreased in those experiencing grade 3-4 cardiac events (p < 0.001). We observed a high incidence of cardiac toxicity associated with significant mortality in AML.

Culturally appropriate storytelling to improve blood pressure: a randomized trial.

BACKGROUND: Storytelling is emerging as a powerful tool for health promotion in vulnerable populations. However, these interventions remain largely untested in rigorous studies. OBJECTIVE: To test an interactive storytelling intervention involving DVDs. DESIGN: Randomized, controlled trial in which comparison patients received an attention control DVD. Separate random assignments were performed for patients with controlled or uncontrolled hypertension. (ClinicalTrials.gov registration number: NCT00875225) SETTING: An inner-city safety-net clinic in the southern United States. PATIENTS: 230 African Americans with hypertension. INTERVENTION: 3 DVDs that contained patient stories. Storytellers were drawn from the patient population. MEASUREMENTS: The outcomes were differential change in blood pressure for patients in the intervention versus the comparison group at baseline, 3 months, and 6 to 9 months. RESULTS: 299 African American patients were randomly assigned between December 2007 and May 2008 and 76.9% were retained throughout the study. Most patients (71.4%) were women, and the mean age was 53.7 years. Baseline mean systolic and diastolic pressures were similar in both groups. Among patients with baseline uncontrolled hypertension, reduction favored the intervention group at 3 months for both systolic (11.21 mm Hg [95% CI, 2.51 to 19.9 mm Hg]; P = 0.012) and diastolic (6.43 mm Hg [CI, 1.49 to 11.45 mm Hg]; P = 0.012) blood pressures. Patients with baseline controlled hypertension did not significantly differ over time between study groups. Blood pressure subsequently increased for both groups, but between-group differences remained relatively constant. LIMITATION: This was a single-site study with 23% loss to follow-up and only 6 months of follow-up. CONCLUSION: The storytelling intervention produced substantial and significant improvements in blood pressure for patients with baseline uncontrolled hypertension. PRIMARY FUNDING SOURCE: Finding Answers: Disparities Research for Change, a national program of the Robert Wood Johnson Foundation.