Treatment patterns of patients with HR+/HER2- metastatic breast cancer receiving CDK4/6 inhibitor-based regimens: a cohort study in the French nationwide healthcare database.

PURPOSE: To assess real-world treatment patterns in patients diagnosed with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer (mBC) who received cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in combination with an aromatase inhibitor (AI) or fulvestrant at first line. METHODS: Patient characteristics, treatment history, and outcomes data were extracted from the French 'Système National des Données de Santé' (SNDS) database for patients diagnosed with HR+/HER2- mBC between January 2014 and June 2019 and who received combination therapy with a CDK4/6 inhibitor and endocrine therapy. Kaplan-Meier methodology was used to assess time to next treatment (TTNT) and time to treatment discontinuation (TTTD). RESULTS: The cohort comprised 6061 patients including 4032 patients who received CDK4/6 inhibitors + AIs and 2029 patients who received CDK4/6 inhibitors + fulvestrant. Median follow-up was 13.5 months (IQR 9.5-18.1). The median TTTD of first line treatment with CDK4/6 inhibitors + AIs and CDK4/6 inhibitors + fulvestrant was 17.3 months (95% CI 16.8-17.9) and 9.7 months (95% CI 9.0-10.2), respectively. Chemotherapy was the most common second line therapy. Median TTTD of subsequent treatment lines was progressively shorter following first line treatment with CDK4/6 inhibitors + AIs (2nd line: 4.6 months (95% CI 4.4-4.9) and with CDK4/6 inhibitors + fulvestrant (2nd line: 4.7 months (95% CI 4.3-5.1). TTNT was longer than TTTD across lines of therapy. CONCLUSION: This real-world analysis confirms the effectiveness of CDK4/6 inhibitor-based regimens in French patients and highlights the frequent use of chemotherapy as second line therapy.

Critical Comments by Food and Drug Administration Reviewers on Patient-Reported Outcomes in Food and Drug Administration Regulatory Submissions (2018-2021).

OBJECTIVES: This article examined the inclusion of patient-reported outcome (PRO) data in new drug applications (NDAs) submitted to the Food and Drug Administration (FDA) and approved from 2018 to 2021. The importance of assessing PROs, which capture patients' perspectives on the disease and treatment experience, has been underscored by many stakeholders, including regulatory authorities. Despite the increasing inclusion of PRO assessments in registration trials, inclusion of language related to PRO results in approved product labeling varies widely. METHODS: This study examined FDA submission packages for NDAs approved by the FDA from 2018 to 2021 to identify critical reviewer comments related to PROs. Comments were identified and categorized by the type of criticism. Reviewers considered both oncology and nononcology indications. RESULTS: Assessment of PROs was included in 66.2% of the 210 submissions reviewed. Critical comments were identified in 45.3% of these applications; comments most commonly related to statistical analysis considerations, fit for purpose, and study design. Other categories of critical comment included data quality, lack of treatment benefit, administrative considerations, and miscellaneous issues. Differences were observed between oncology and nononcology NDAs with regard to the number and type of comments included in each of these categories. The findings highlight the importance of planning statistical analyses, establishing content validity, carefully considering study design, maximizing data quality, and demonstrating treatment benefit, among other issues. CONCLUSIONS: Overall, this study offers insight into the landscape of PRO data included in recently approved NDAs, along with recommendations for improving the quality and reporting of PROs in clinical trials.

Progression-free survival and quality of life in metastatic breast cancer: The patient perspective.

INTRODUCTION: Treatment advances for metastatic breast cancer (mBC) have improved overall survival (OS) in some mBC subtypes; however, there remains no cure for mBC. Considering the use of progression-free survival (PFS) and other surrogate endpoints in clinical trials, we must understand patient perspectives on measures used to assess treatment efficacy. OBJECTIVE: To explore global patient perceptions of the concept of PFS and its potential relation to quality of life (QoL). MATERIALS AND METHODS: Virtual roundtables in Europe and the United States and interviews in Japan with breast cancer patients, patient advocates, and thought leaders. Discussions were recorded, transcribed, and analyzed thematically. RESULTS: Lengthened OS combined with no worsening or improvement in QoL remain the most important endpoints for mBC patients. Time when the disease is not progressing is meaningful to patients when coupled with improvements in QoL and no added treatment toxicity. Clinical terminology such as "PFS" is not well understood, and participants underscored the need for patient-friendly terminology to better illustrate the concept. Facets of care that patients with mBC value and that may be related to PFS include relief from cancer-related symptoms and treatment-related toxicities as well as the ability to pursue personal goals. Improved communication between patients and providers on managing treatment-related toxicities and addressing psychosocial challenges to maintain desired QoL is needed. CONCLUSION: While OS and QoL are considered the most relevant endpoints, patients also value periods of time without disease progression. Incorporation of these considerations into the design and conduct of future clinical trials in mBC, as well as HTA and reimbursement decision-making, is needed to better capture the potential value of a therapeutic innovation.

Adherence to Chronic Kidney Disease Screening Guidelines Among Patients With Type 2 Diabetes in a US Administrative Claims Database.

OBJECTIVE: To examine the screening rates for kidney damage and function among patients with type 2 diabetes (T2D) and chronic kidney disease stage at diabetes diagnosis using a US administrative claims database. PATIENTS AND METHODS: This cohort study used a claims database enriched with laboratory results data. Patients with T2D (defined as 1 inpatient or 2 outpatient claims for diabetes), aged 18 years or older, and with at least 1 year of follow-up enrollment were identified. Patients with type 1 diabetes, kidney disease, or other related conditions at baseline were excluded. We estimated screening rates using laboratory orders for serum creatinine and estimated glomerular filtration rate (eGFR) measurement and urine albumin to creatinine ratio (UACR). Chronic kidney disease severity was reported using the Kidney Disease: Improving Global Outcomes classification based on laboratory results. RESULTS: A total of 1,881,447 patients with T2D were eligible for analysis. Mean ± SD age was 63.1±13.1 years; 947,150 patients (50.3%) were male. Serum creatinine tests were ordered within 14 days of the index date among 290,722 patients of 622,915 (46.7%) patients with newly-recognized T2D. Overall, 1,595,964 patients (84.8%) had at least one serum creatinine test ordered during the 1-year follow-up period. Fewer patients received a UACR test during follow-up (814,897 [43.3%]). Less than half of all patients with T2D received a laboratory test order for both serum creatinine and urine albumin measurements during the follow-up period. CONCLUSION: Physicians treating patients with diabetes are selectively adhering to chronic kidney disease screening guidelines, as indicated by high rates of eGFR testing, but less frequent UACR testing. Despite recommendations to monitor both eGFR and UACR, less than half of patients were screened for albuminuria during the 1-year follow-up.

Impact of adverse childhood experiences on cardiovascular disease risk factors in adulthood among Mexican women.

BACKGROUND: Childhood adversities are prevalent worldwide and might affect adult cardiovascular health. However, in middle-income countries such as Mexico, research on the impact of childhood adversities on cardiovascular disease (CVD) in adulthood is lacking. OBJECTIVE: To evaluate the prevalence of adverse childhood experiences (ACEs) and their association with risk factors for CVD in adult Mexican women. PARTICIPANTS AND SETTING: The study population comprised 9853 women from the Mexican Teachers´ Cohort. METHODS: Participants responded to an online questionnaire including a 10-item instrument on ACEs and questions on CVD risk factors, between 2014 and 2017. Multivariate logistic regression models were used to evaluate the association between ACEs and adult behavioral and medical CVD risk factors. RESULTS: About 61% of participants reported at least one ACE and 14% reported four or more. After multivariable adjustment, women who reported ≥4 ACEs had 58% (95%CI 1.37, 1.81) higher odds of having ever smoked and 17% (95%CI 0.69, 0.99) lower odds of being physically active, compared with women who reported no ACEs. Women who reported ≥4 ACEs also had higher odds of hypertension (OR = 1.19; 95%CI 1.00, 1.43), diabetes (OR = 1.49; 95%CI 1.13, 1.96), high cholesterol (OR = 1.49; 95%CI 1.26, 1.75), and obesity (OR = 1.37; 95%CI 1.19, 1.57). In addition, individual ACE components were independently associated with several CVD risk factors. CONCLUSION: ACEs are common and associated with CVD risk factors in adult Mexican women.