Camrelizumab combined with apatinib and nanoparticle albumin-bound paclitaxel in lung adenocarcinoma (CAPAP-lung): a single-arm phase II study.

Background: Platinum-doublet chemotherapy plus immunotherapy has been the standard of care for the first-line treatment of advanced non-small cell lung cancer lacking actional driver mutations. However, optimization of drug combinations is still needed to find a better balance between therapeutic efficacy and safety in the immunotherapy era. We aimed to investigate the efficacy and safety of platinum-free albumin bound paclitaxel (nab-paclitaxel) combined with camrelizumab and apatinib as first-line treatment for patients with advanced lung adenocarcinoma. Methods: In this multicenter open-label, single-arm phase II trial, patients with systemic treatment-naïve advanced lung adenocarcinoma without epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutations received a rational-based combination of camrelizumab (200 mg intravenously, day one), apatinib (250 mg, q.d., five continuous days per week), and nab-paclitaxel (135 mg/m2 intravenously, days one and eight) every three weeks for four to six cycles in China. Patients with controlled disease were maintained with camrelizumab and apatinib. The primary end point was progression-free survival (PFS). This trial is registered with ClinicalTrials.gov (No. NCT04459078). Findings: Between August 26, 2020 and May 20, 2022, 64 patients were enrolled. The median PFS was 14.3 (95% CI: 9.9, not reached) months. The confirmed objective response rate was 64.1% (95% CI: 51.1, 75.7). The grade 3-4 hematologic treatment-related adverse events (TRAEs) were decreased neutrophil count (14.1%), decreased white blood cell count (7.8%), and anemia (3.1%). The most common non-hematologic TRAEs of grade 3-4 were increased alanine transaminase (18.8%) and aspartate transaminase (15.6%). No treatment-related death occurred. The quality of life was on average not clinically meaningful worse through treatment cycle 14. Interpretation: Nab-paclitaxel plus camrelizumab and apatinib showed clinically meaningful anti-tumor activity and manageable safety, with few hematologic toxicities, and might be a potential treatment option in patients with advanced lung adenocarcinoma lacking EGFR/ALK mutations. Funding: Heath Research Foundation of Chinese Society of Clinical Oncology, Hunan Provincial Natural Science Foundation of China, Hunan Cancer Hospital Climb Plan, Sister Institution Network Fund of The University of Texas MD Anderson Cancer Center, The Science and Technology Innovation Program of Hunan Province, and Suzhou Sheng Diya Biomedical Co., Ltd, a subsidiary of Jiangsu Hengrui Pharmaceuticals Co., Ltd. (Shanghai, China).

Camrelizumab Plus Apatinib and Temozolomide as First-Line Treatment in Patients With Advanced Acral Melanoma: The CAP 03 Phase 2 Nonrandomized Clinical Trial.

Importance: Acral melanoma, known for low tumor mutation burden, responds poorly to immunotherapy. A standard therapy is still lacking. Objective: To investigate the activity and safety of camrelizumab (an anti-programmed cell death-1 antibody) plus apatinib (a vascular endothelial growth factor receptor 2 inhibitor) and temozolomide as first-line treatment in patients with advanced acral melanoma. Design, Setting, and Participants: In this single-arm, single-center, phase 2 nonrandomized clinical trial, patients with treatment-naive unresectable stage III or IV acral melanoma were enrolled at Peking University Cancer Hospital and Institute between June 4, 2020, and August 24, 2021. The data cutoff date was April 10, 2022. Interventions: Patients received 4-week cycles of intravenous camrelizumab, 200 mg, every 2 weeks; oral apatinib 250 mg, once daily; and intravenous temozolomide, 200 mg/m2, once daily on days 1 to 5 until disease progression or unacceptable toxic effects. Main Outcomes and Measures: The primary end point was objective response rate as assessed by investigators according to the Response Evaluation Criteria In Solid Tumors (version 1.1). Secondary end points included progression-free survival, time to response, duration of response, disease control rate, overall survival, and safety. Results: A total of 50 patients (32 men [64%]; median age, 57 years [IQR, 52-62 years]) were enrolled and received treatment. The median follow-up duration was 13.4 months (IQR, 9.6-16.2 months). The objective response rate was 64.0% (32 of 50; 95% CI, 49.2%-77.1%). The median time to response and duration of response were 2.7 months (IQR, 0.9-2.9 months) and 17.5 months (95% CI, 12.0 to not reached), respectively. The disease control rate was 88.0% (44 of 50; 95% CI, 75.7%-95.5%). The estimated median progression-free survival was 18.4 months (95% CI, 10.6 to not reached). The median overall survival was not reached. The most common grade 3 or 4 treatment-related adverse events were increased gamma-glutamyltransferase levels (15 [30%]), decreased neutrophil count (11 [22%]), increased conjugated bilirubin levels (10 [20%]), and increased aspartate aminotransferase levels (10 [20%]). No treatment-related deaths occurred. Conclusions and Relevance: The findings of this nonrandomized clinical trial suggest that camrelizumab plus apatinib and temozolomide may be a potential first-line treatment option for patients with advanced acral melanoma, which warrants further validation in a randomized clinical trial. Trial Registration: ClinicalTrials.gov Identifier: NCT04397770.

Sodium and Potassium Excretion of Schoolchildren and Relationship with Their Family Excretion in China.

This cross-sectional study aimed to assess 24-h urinary sodium and potassium excretion in children and the relationships with their family excretion. Using the baseline data of a randomized trial conducted in three cities of China in 2018, a total of 590 children (mean age 8.6 ± 0.4 years) and 1180 adults (mean age 45.8 ± 12.9 years) from 592 families had one or two complete 24-h urine collections. The average sodium, potassium excretion and sodium-to-potassium molar ratio of children were 2180.9 ± 787.1 mg/d (equivalent to 5.5 ± 2.0 g/d of salt), 955.6 ± 310.1 mg/d and 4.2 ± 1.7 respectively, with 77.1% of the participants exceeding the sodium recommendation and 100% below the proposed potassium intake. In mixed models adjusting for confounders, every 1 mg/d increase in sodium excretion of adult family members was associated with a 0.11 mg/d (95% CI: 0.06 to 0.16, p < 0.0001) increase in sodium excretion of children. The family-child regression coefficient corresponds to 0.20 mg/d (95% CI: 0.15 to 0.26, p < 0.0001) per 1 mg/d in potassium and to 0.36 (95% CI: 0.26 to 0.45, p < 0.0001) in sodium-to-potassium molar ratio. Children in China are consuming too much sodium and significantly inadequate potassium. The sodium, potassium excretion and sodium-to-potassium ratio of children are associated with their family excretions in small to moderate extent. Efforts are warranted to support salt reduction and potassium enhancement in children through comprehensive strategies engaging with families, schools and food environments.

Road to Hierarchical Diabetes Management at Primary Care (ROADMAP) Study in China: Protocol for the Statistical Analysis of a Cluster Randomized Controlled Trial.

BACKGROUND: As the management of type 2 diabetes remains suboptimal in primary care, the Road to Hierarchical Diabetes Management at Primary Care (ROADMAP) study was designed and conducted in diverse primary care settings to test the effectiveness of a three-tiered diabetes management model of care in China. OBJECTIVE: This paper aims to predetermine the detailed analytical methods for the ROADMAP study before the database lock to reduce potential bias and facilitate transparent analyses. METHODS: The ROADMAP study adopts a community-based, cluster randomized controlled trial design that compares the effectiveness of a tiered diabetes management model on diabetes control with usual care among patients with diabetes over a 1-year study period. The primary outcome is the control rate of glycated hemoglobin (HbA1c) <7% at 1 year. Secondary outcomes include the control rates of ABC (HbA1c, blood pressure, and low-density lipoprotein cholesterol [LDL-C], individual and combined) and fasting blood glucose, and the change in each outcome. The primary analysis will be the log-binomial regression with generalized estimating equation (GEE), which accounts for the clustering within communities, for binary outcomes and linear regression with GEE for continuous outcomes. For both, the baseline value of the analyzed outcome will be the covariate. The other covariate further adjusted models and the repetitive models after multiple imputation (when more than 10% of observations in HbA1c after 1 year are missing) will be used for sensitivity analysis. Five prespecified subgroup analyses have also been planned to explore the heterogeneity of the intervention effects by adding the subgroup variable and its interaction with the intervention to the primary model. RESULTS: This plan has been finalized, approved, and signed off by the principle investigator, co-principle investigator, and lead statisticians as of November 22, 2019, and made public on the institutional website without any knowledge of intervention allocation. Templates for the main figure and tables are presented. CONCLUSIONS: This statistical analysis protocol was developed for the main results of the ROADMAP study by authors blinded to group allocation and with no access to study data, which will guarantee the transparency and reduce potential bias during statistical analysis. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IOC-17011325; https://tinyurl.com/ybpr9xrq. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/18333.