Bempegaldesleukin plus Nivolumab in First-line Metastatic Urothelial Carcinoma: Results from PIVOT-02.

BACKGROUND: Despite recent changes in the treatment landscape, there remains an unmet need for effective, tolerable, chemotherapy-free treatments for patients with advanced/metastatic urothelial carcinoma (mUC), especially cisplatin-ineligible patients. OBJECTIVE: To evaluate the immunostimulatory interleukin-2 cytokine prodrug bempegaldesleukin (BEMPEG) plus nivolumab in patients with advanced/mUC from the phase 2 multicenter PIVOT-02 study. DESIGN, SETTING, AND PARTICIPANTS: This open-label, multicohort phase 1/2 study enrolled patients with previously untreated locally advanced/surgically unresectable or mUC (N = 41). INTERVENTION: Patients received BEMPEG 0.006 mg/kg plus nivolumab 360 mg intravenously every 3 wk. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary objectives were safety and the objective response rate (ORR) in patients with measurable disease at baseline and at least one postbaseline tumor response assessment (response-evaluable). Secondary objectives were overall survival (OS) and progression-free survival (PFS). Exploratory biomarker analyses via univariate logistic regression were performed to test the association between potential biomarkers (CD8+ tumor-infiltrating lymphocytes, tumor mutational burden, and IFN-γ gene expression profile) and response. RESULTS AND LIMITATIONS: The ORR was 35% (13/37 evaluable patients) and the complete response rate was 19% (7/37 patients); the median duration of response was not reached. Median PFS was 4.1 mo (95% confidence interval [CI] 2.1-8.7) and median OS was 23.7 mo (95% CI 15.8-not reached). Overall, 40/41 patients (98%) experienced at least one treatment-related adverse event (TRAE); grade 3/4 TRAEs occurred in 11 patients (27%), most commonly pyrexia (4.9%; 2 patients). Exploratory biomarker analyses showed no association between biomarkers and response. Limitations include the small sample size and single-arm design. CONCLUSIONS: BEMPEG plus nivolumab was well tolerated and showed antitumor activity as first-line treatment in patients with locally advanced/mUC. PATIENT SUMMARY: We investigated an immune-stimulating prodrug called bempegaldesleukin plus the antibody nivolumab as the first therapy for patients with advanced or metastatic cancer of the urinary tract. This combination had manageable treatment-related side effects and was effective in a subset of patients. This trial is registered at ClinicalTrials.gov as NCT02983045.

Bempegaldesleukin plus nivolumab in first-line renal cell carcinoma: results from the PIVOT-02 study.

BACKGROUND: Immune checkpoint inhibitor-based combinations have expanded the treatment options for patients with renal cell carcinoma (RCC); however, tolerability remains challenging. The aim of this study was to evaluate the safety and efficacy of the immunostimulatory interleukin-2 cytokine prodrug bempegaldesleukin (BEMPEG) plus nivolumab (NIVO) as first-line therapy in patients with advanced clear-cell RCC. METHODS: This was an open-label multicohort, multicenter, single-arm phase 1/2 study; here, we report results from the phase 1/2 first-line RCC cohort (N=49). Patients received BEMPEG 0.006 mg/kg plus NIVO 360 mg intravenously every 3 weeks. The primary objectives were safety and objective response rate (ORR; patients with measurable disease at baseline and at least one postbaseline tumor response assessment). Secondary objectives included overall survival (OS) and progression-free survival (PFS). Exploratory biomarker analyses: association between baseline biomarkers and ORR. RESULTS: At a median follow-up of 32.7 months, the ORR was 34.7% (17/49 patients); 3/49 patients (6.1%) had a complete response. Of the 17 patients with response, 14 remained in response for >6 months, and 6 remained in response for >24 months. Median PFS was 7.7 months (95% CI 3.8 to 13.9), and median OS was not reached (95% CI 37.3 to not reached). Ninety-eight per cent (48/49) of patients experienced ≥1 treatment-related adverse event (TRAE) and 38.8% (19/49) had grade 3/4 TRAEs, most commonly syncope (8.2%; 4/49) and increased lipase (6.1%; 3/49). No association between exploratory biomarkers and ORR was observed. Limitations include the small sample size and single-arm design. CONCLUSIONS: BEMPEG plus NIVO showed preliminary antitumor activity as first-line therapy in patients with advanced clear-cell RCC and was well tolerated. These findings warrant further investigation.

Trends in Yoga, Tai Chi, and Qigong Use Among US Adults, 2002-2017.

OBJECTIVES: To examine the characteristics and temporal trends of yoga, tai chi, and qigong (YTQ) use among US adults. METHODS: Using the 2002, 2007, 2012, and 2017 National Health Interview Surveys, we examined the prevalence, patterns, and predicting factors of YTQ use by Taylor series linear regression, the Wald F χ2 test, and multivariable logistic regression models (n = 116 404). RESULTS: YTQ use increased from 5.8% in 2002 to 14.5% in 2017 (P ≤ .001). Only 6.6% of YTQ users were referred by their medical doctors, and approximately one third disclosed their use of YTQ to medical professionals. Reasons for using YTQ included (1) YTQ was beneficial, (2) YTQ focused on the whole person, and (3) YTQ was natural. Acute and chronic pain, arthritis, and depression were the top 3 medical conditions for which people used YTQ the most. CONCLUSIONS: YTQ use is increasing substantially, mainly because of its natural and holistic healing approach toward health and chronic diseases. Future studies aiming to explore how to best integrate YTQ into the current health care system are warranted.

Applicability of the Curaçao Criteria for the Diagnosis of Hereditary Hemorrhagic Telangiectasia in the Pediatric Population.

OBJECTIVE: To evaluate the accuracy of the clinical Curaçao criteria in the diagnosis of hereditary hemorrhagic telangiectasia (HHT) in children and adolescents. STUDY DESIGN: This was a retrospective, multicenter chart review of 673 patients evaluated between 2002 and 2016; 290 were eligible for the study. Genetic testing for a pathogenic mutation was considered the gold standard against which the clinical Curaçao criteria were compared. Patients were divided into 4 age categories: 0-5, 6-10, 11-15, and 16-21-years. Sensitivity and specificity were calculated for each age group, and for the overall population. RESULTS: Overall the Curaçao criteria had a sensitivity of 68% (95% CI 60%-76%) and a specificity of 98% (95% CI 91%-100%). Sensitivity was lowest in the 0- to 5-year group, and increased with advancing age. The Curaçao criteria had the highest sensitivity in the 16- to 21-year-olds. Specificity was 100% in all age groups except for the 11- to 15-year-olds. CONCLUSIONS: This study evaluated the use of the Curaçao criteria for the diagnosis of HHT in the pediatric population with a family history of HHT. In those between the age of 0 and 21 years who meet 1 criterion (unlikely HHT) or 2 criteria (possible HHT), genetic testing is preferred for diagnosis. The Curaçao criteria appear to reliably diagnose HHT in children and adolescents who meet 3 or 4 criteria (definite HHT).

Evaluation of Diabetic Retinal Screening and Factors for Ophthalmology Referral in a Telemedicine Network.

Importance: Retinal telescreening for evaluation of diabetic retinopathy (DR) in the primary care setting may be useful in reaching rural and underserved patients. Objectives: To evaluate telemedicine retinal screenings for patients with type 1 or 2 diabetes and identify factors for ophthalmology referral in the North Carolina Diabetic Retinopathy Telemedicine Network. Design, Setting, and Participants: A preimplementation and postimplementation evaluation was conducted from January 6, 2014, to November 1, 2015, at 5 primary care clinics serving rural and underserved populations in North Carolina among 1787 adult patients with type 1 or 2 diabetes who received primary care at the clinics and obtained retinal telescreening to determine the presence and severity of DR. A total of 1661 patients with complete data were included in the statistical analysis. Intervention: Nonmydriatic fundus photography with remote interpretation by an expert. Main Outcomes and Measures: Number of patients recruited, level of detected DR, change in rates of screening, rate of ophthalmology referral, percentage of completed referrals, and patient characteristics associated with varying levels of DR. Results: Of the 1661 patients (1041 women and 620 men; mean [SD] age, 55.4 [12.7] years), 1323 patients (79.7%) had no DR, 183 patients (11.0%) had DR without a need for an ophthalmology referral, and 155 patients (9.3%) had DR with a need for an ophthalmology referral. The mean rate of screening for DR before implementation of the program was 25.6% (1512 of 5905), which increased to 40.4% (1884 of 4664) after implementation. A total of 93 referred patients (60.0%) completed an ophthalmology referral visit within the study period. Older patients (odds ratio [OR], 1.28; 95% CI, 1.11-1.48) and African American patients (OR, 1.84; 95% CI, 1.24-2.73) or other racial/ethnic minorities (OR, 2.19; 95% CI, 1.16-4.11) had greater odds of requiring an ophthalmology referral compared with white and/or younger patients. Patients with higher hemoglobin A1c levels (OR, 1.19 per unit change; 95% CI, 1.13-1.25 per unit change) and longer duration of diabetes (OR, 1.76 per decade; 95% CI, 1.53-2.02 per decade) had greater odds of DR requiring an ophthalmology referral. History of stroke (OR, 1.65; 95% CI, 1.10-2.48) and kidney disease (OR, 1.59; 95% CI, 1.10-2.31) were strongly associated with DR and ophthalmology referral. Conclusions and Relevance: When implemented in the primary care setting, retinal telescreening increased the rate of evaluation for DR for patients in rural and underserved settings. This strategy may also increase access to care for minorities and patients with DR requiring treatment.