Real-World Perspectives and Practices for Pneumonitis/Interstitial Lung Disease Associated With Trastuzumab Deruxtecan Use in Human Epidermal Growth Factor Receptor 2-Expressing Metastatic Breast Cancer.

Trastuzumab deruxtecan (T-DXd) is an antibody drug conjugate with a topoisomerase I payload that targets the human epidermal growth factor receptor 2 (HER2). T-DXd is approved for patients with previously treated HER2-positive or HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/ISH-) metastatic/unresectable breast cancer (BC). In a second-line HER2-positive metastatic BC (mBC) population (DESTINY-Breast03 [ClinicalTrials.gov identifier: NCT03529110]), T-DXd demonstrated significantly improved progression-free survival (PFS) over ado-trastuzumab emtansine (12-month rate: 75.8% v 34.1%; hazard ratio, 0.28; P < .001), and in patients with HER2-low mBC treated with one prior line of chemotherapy (DESTINY-Breast04 [ClinicalTrials.gov identifier: NCT03734029]), T-DXd demonstrated significantly longer PFS and overall survival than physician's choice chemotherapy (10.1 v 5.4 months; hazard ratio, 0.51; P < .001, and 23.4 v 16.8 months; hazard ratio, 0.64; P < .001, respectively).Interstitial lung disease (ILD) is an umbrella term used for a group of diseases characterized by lung injury including pneumonitis, which can lead to irreversible lung fibrosis. ILD is a well-described adverse event associated with certain anticancer therapies, including T-DXd. An important part of T-DXd therapy for mBC consists of monitoring for and managing ILD. Although information on ILD management strategies is included in the prescribing information, additional information on patient selection, monitoring, and treatment can be beneficial in routine clinical practice. The objective of this review is to describe real-world, multidisciplinary clinical practices and institutional protocols used for patient selection/screening, monitoring, and management related to T-DXd-associated ILD.

Initial vancomycin dosing in pediatric oncology and stem cell transplant patients.

BACKGROUND: Gram-positive bacteremia is a common infection in pediatric oncology and stem cell transplant (SCT) patients requiring therapy with vancomycin. Optimal dosing of vancomycin in this patient population has not been well established. METHODS: All pediatric oncology and SCT patients receiving vancomycin between October 2006 and March 2007 were included in this study. Therapeutic levels were defined as levels between 10 and 15 mg/dL and low therapeutic levels were between 5 and 9 mg/dL. Information regarding any recent or concurrent nephrotoxic medications was collected. RESULTS: Fifty-six patients received 82 courses of vancomycin during the study period. More patients (53.7%) received vancomycin for empiric therapy and 78% had recent or concurrent use of nephrotoxic medications. Using standardized vancomycin dosing guided by a computerized provider order entry system, there were significantly more patients who were in the subtherapeutic range than the supratherapeutic range (P=0.0023). There were also significantly more patients in the low therapeutic than the therapeutic range (P<0.0001). A small number of courses (3.5%) were associated with supratherapeutic levels. There was no association between the concurrent or recent use of nephrotoxic medications and vancomycin levels. CONCLUSIONS: Pediatric oncology and SCT patients with normal renal function require higher daily vancomycin doses than other pediatric patients.