Sacituzumab Govitecan in Combination With Pembrolizumab for Patients With Metastatic Urothelial Cancer That Progressed After Platinum-Based Chemotherapy: TROPHY-U-01 Cohort 3.

PURPOSE: Pembrolizumab is standard therapy for patients with metastatic urothelial cancer (mUC) who progress after first-line platinum-based chemotherapy; however, only approximately 21% of patients respond. Sacituzumab govitecan (SG) is a trophoblast cell surface antigen-2-directed antibody-drug conjugate with US Food and Drug Administration-accelerated approval to treat patients with locally advanced or mUC who previously received platinum-based chemotherapy and a checkpoint inhibitor (CPI). Here, we report the primary analysis of TROPHY-U-01 cohort 3. METHODS: TROPHY-U-01 (ClinicalTrials.gov identifier: NCT03547973) is a multicohort, open-label phase II study. Patients were CPI-naïve and had mUC progression after platinum-based chemotherapy in the metastatic setting or ≤12 months in the (neo)adjuvant setting. Patients received 10 mg/kg of SG once on days 1 and 8 and 200 mg of pembrolizumab once on day 1 of 21-day cycles. The primary end point was objective response rate (ORR) per central review. Secondary end points included clinical benefit rate (CBR), duration of response (DOR) and progression-free survival (PFS) per central review, and safety. RESULTS: Cohort 3 included 41 patients (median age 67 years; 83% male; 78% visceral metastases [29% liver]). With a median follow-up of 14.8 months, the ORR was 41% (95% CI, 26.3 to 57.9; 20% complete response rate), CBR was 46% (95% CI, 30.7 to 62.6), median DOR was 11.1 months (95% CI, 4.8 to not estimable [NE]), and median PFS was 5.3 months (95% CI, 3.4 to 10.2). The median overall survival was 12.7 months (range, 10.7-NE). Grade ≥3 treatment-related adverse events occurred in 61% of patients; most common were neutropenia (37%), leukopenia (20%), and diarrhea (20%). CONCLUSION: SG plus pembrolizumab demonstrated a high response rate with an overall manageable toxicity profile in patients with mUC who progressed after platinum-based chemotherapy. No new safety signals were detected. These data support further evaluation of SG plus CPI in mUC.

Effect of antibacterial home cleaning and handwashing products on infectious disease symptoms: a randomized, double-blind trial.

BACKGROUND: Despite the widespread household use of cleaning and personal hygiene products containing antibacterial ingredients, their effects on the incidence of infectious disease symptoms have not been studied. OBJECTIVE: To evaluate the effect of antibacterial cleaning and handwashing products for consumers on the occurrence of infectious disease symptoms in households. DESIGN: Randomized, double-blind clinical trial. SETTING: Northern Manhattan inner-city neighborhood, New York. PARTICIPANTS: 238 primarily Hispanic households (1178 persons) that included at least one preschool-age child. INTERVENTIONS: Households were randomly assigned to use either antibacterial or nonantibacterial products for general cleaning, laundry, and handwashing. All products were commercially available, but the packaging was blinded and the products were provided free to participants. MEASUREMENTS: Hygiene practices and infectious disease symptoms were monitored by weekly telephone calls, monthly home visits, and quarterly interviews for 48 weeks. RESULTS: Symptoms were primarily respiratory: During 26.2% (717 of 2736) of household-months, 23.3% (640 of 2737) of household-months, and 10.2% (278 of 2737) of household-months, one or more members of the household had a runny nose, cough, or sore throat, respectively. Fever was present during 11% (301 of 2737) of household-months, vomiting was present in 2.2% (61 of 2737), diarrhea was present in 2.5% (69 of 2737), and boils or conjunctivitis were present in 0.77% (21 of 2737). Differences between intervention and control groups were not significant for any symptoms (all unadjusted and adjusted relative risks included 1.0) or for numbers of symptoms (overall incidence density ratio, 0.96 [95% CI, 0.82 to 1.12]). CONCLUSIONS: The tested antibacterial products did not reduce the risk for symptoms of viral infectious diseases in households that included essentially healthy persons. This does not preclude the potential contribution of these products to reducing symptoms of bacterial diseases in the home.

Predictors of infectious disease symptoms in inner city households.

BACKGROUND: Despite the fact that hygienic practices have been associated with reduced risk of infection for decades, the potential role of specific home hygiene and cleaning practices in reducing risk have not been explicated. OBJECTIVE: This study aimed to determine the incidence and predictors of infectious disease symptoms over a 48-week period in inner city households. METHODS: Cleaning and hygiene practices and the incidence of infectious disease symptoms were closely monitored prospectively for 48 months in 238 households. Each household was contacted by trained interviewers weekly via telephone, was visited monthly, and underwent an extensive home interview quarterly. RESULTS: The incidence of new symptoms in the month before quarterly home visits ranged from 8.9% to 12.4% for individuals and from 32% to 39.7% for households. Four factors were significantly associated with infection. Drinking only bottled water increased risk (relative risk [RR], 2.1; 95% confidence interval [CI], 1.2-3.7). Using hot water (RR, 0.7; 95% CI,.5-.9) and bleach (RR, 0.29; 95% CI,.23-.66) for laundry and reporting that germs were most likely to be picked up in the kitchen (RR, 0.5; 95% CI,.3-.8) were protective. No other hygiene practices, including hand washing, were associated with infection risk. CONCLUSIONS: Further studies of a potential role for bottled water in infections are warranted, as is a renewed appreciation for the potential protective role of laundry practices such as using bleach and hot water.