Real-world safety and effectiveness of anamorelin for cancer cachexia: Interim analysis of post-marketing surveillance in Japan.

BACKGROUND: Anamorelin was approved in Japan in 2021 to treat cancer cachexia associated with non-small cell lung, gastric, pancreatic, or colorectal cancers. Post-marketing surveillance is being conducted to evaluate the real-world safety and effectiveness of anamorelin. METHODS: This prospective, observational surveillance registered all patients who started treatment with anamorelin after April 21, 2021. Hyperglycemia, hepatic impairment, conduction disorders, and their associated adverse events related to treatment were defined as main safety specifications. Body weight (BW) and appetite were assessed as effectiveness specifications. RESULTS: This analysis was based on data as of January 21, 2023. The safety and effectiveness analysis sets included 6016 and 4511 patients, respectively. Treatment-related adverse events in ≥1% of patients were hyperglycemia (3.9%) and nausea (2.6%). The incidences of hyperglycemia, hepatic impairment, conduction disorders, and their associated adverse events related to treatment were 4.8%, 1.2%, and 1.1%, respectively. The mean changes (standard error [SE]) in BW from baseline to weeks 3, 12, 24, and 52 were 0.64 (0.05) kg, 1.19 (0.12) kg, 1.40 (0.21) kg, and 1.42 (0.39) kg, respectively. The mean changes (SE) in Functional Assessment of Anorexia/Cachexia Treatment 5-item Anorexia Symptom Scale total scores from baseline to weeks 3, 12, 24, and 52 were 3.2 (0.09), 4.8 (0.18), 5.2 (0.30), and 5.3 (0.47), respectively, exceeding the clinically meaningful improvement score (2.0 points). CONCLUSION: The overall safety of anamorelin raised no new safety concerns, although continued caution may be required for hyperglycemia and nausea. Improvements in BW and appetite were also observed in real-world clinical settings.

[The Second Web Questionnaire Survey on Cancer Cachexia Japanese Evidence for Patients Of Cancer Cachexia â ¡ (J-EPOCC â ¡)-Disease Awareness and Issues Related to Cancer Cachexia Among Healthcare Professionals].

In 2019, the Cancer Cachexia Web Questionnaire Survey(J-EPOCC)was conducted among cancer patients, their families and healthcare professionals in Japan, and it showed that the term"cancer cachexia"was highly recognized among health care professionals, whereas the staging and criteria for cancer cachexia defined by European Palliative Care Research Collaborative( EPCRC)was less understood. Also, many healthcare professionals tended to consider the term"cancer cachexia" as the terminal stage of cancer, and most of them lacked the knowledge that cancer cachexia is a disease complication which is potentially developed from the early stage of cancer. Since anamorelin was approved in 2021 for"Cancer cachexia in unresectable advanced or recurrent of non-small cell lung cancer, gastric cancer, pancreatic cancer and colorectal cancer", the treatment environment for cancer cachexia has greatly changed. Thus, the second Web Questionnaire Survey(J-EPOCC Ⅱ) was conducted in June 2022 to investigate changes in the problem awareness of cancer cachexia, especially appetite loss and weight loss, among patients and their families and healthcare professionals1). The results for healthcare professionals showed that the awareness of the staging and criteria has increased among doctors in 2022 compared with 2019, and an increasing number of doctors considered"cancer cachexia"was associated with loss of muscle mass, totally body weight loss, appetite loss and systemic inflammation that may occur in early stages of cancer. On the other hand, awareness of staging and diagnostic criteria for cancer cachexia has not remarkably changed among medical staff since 2019, with levels of awareness varying among those with different job categories. Therefore, in order to achieve early detection and intervention of cancer cachexia, it is necessary to raise the awareness of cancer cachexia among not only doctors but also medical staff by increasing their opportunities to get to know the disease condition, diagnosis, and treatment of cancer cachexia.

[The Second Web Questionnaire Survey on Cancer Cachexia Japanese Evidence for Patients Of Cancer Cachexiaâ ¡ (J-EPOCCâ ¡)-Challenges in Early Detection and Early Intervention for Appetite Loss and Weight Loss During Cancer Treatment].

In 2019, the Cancer Cachexia Web Questionnaire Survey(J-EPOCC), conducted among cancer patients, their families and healthcare professionals in Japan showed that nearly half of patients who had experienced appetite loss or weight loss during cancer treatment had not consulted with healthcare professionals about their symptoms, and it meant that patients missed the opportunity to receive medical intervention. Since anamorelin was approved in 2021 fo"r Cancer cachexia in non- small cell lung cancer, gastric cancer, pancreatic cancer and colorectal cancer", the treatment environment for cancer cachexia has greatly changed. Thus, the second Web Questionnaire Survey(J-EPOCCⅡ)was conducted in June 2022 to investigate changes in the problem awareness of cancer cachexia, especially appetite loss and weight loss, among patients and their family and healthcare professionals. The results showed that there was no apparent change in awareness of appetite loss and weight loss, suggesting many patients may miss treatment opportunities. Further disease awareness is required among patients and their families to enhance the understanding of the significance of therapeutic interventions for appetite loss or weight loss, and to call their attention for early detection and treatment.

Machine learning models for prediction of HF and CKD development in early-stage type 2 diabetes patients.

Chronic kidney disease (CKD) and heart failure (HF) are the first and most frequent comorbidities associated with mortality risks in early-stage type 2 diabetes mellitus (T2DM). However, efficient screening and risk assessment strategies for identifying T2DM patients at high risk of developing CKD and/or HF (CKD/HF) remains to be established. This study aimed to generate a novel machine learning (ML) model to predict the risk of developing CKD/HF in early-stage T2DM patients. The models were derived from a retrospective cohort of 217,054 T2DM patients without a history of cardiovascular and renal diseases extracted from a Japanese claims database. Among algorithms used for the ML, extreme gradient boosting exhibited the best performance for CKD/HF diagnosis and hospitalization after internal validation and was further validated using another dataset including 16,822 patients. In the external validation, 5-years prediction area under the receiver operating characteristic curves for CKD/HF diagnosis and hospitalization were 0.718 and 0.837, respectively. In Kaplan-Meier curves analysis, patients predicted to be at high risk showed significant increase in CKD/HF diagnosis and hospitalization compared with those at low risk. Thus, the developed model predicted the risk of developing CKD/HF in T2DM patients with reasonable probability in the external validation cohort. Clinical approach identifying T2DM at high risk of developing CKD/HF using ML models may contribute to improved prognosis by promoting early diagnosis and intervention.