Hepatotoxicity in patients with non-small cell lung cancer treated with sotorasib after prior immunotherapy: a comprehensive clinical and pharmacokinetic analysis.

BACKGROUND: Sotorasib given after immunotherapy could put patients at increased risk of hepatotoxicity. Therefore, there is a need to gain insight into the potential correlation between anti-PD-(L)1 treatment, anti-PD-(L)1 concentrations, sotorasib concentrations, and the incidence of hepatotoxicity during sotorasib. METHODS: Patients with KRASG12C-mutated NSCLC treated with sotorasib were prospectively enrolled in our biomarker cohort study (NCT05221372). Plasma samples were collected prior and during sotorasib treatment for anti-PD-1 and sotorasib concentrations. ALT/AST/ALP/GGT increases were collected prospectively and graded according to CTCAEv5.0. Severe hepatotoxicity was defined as grade ≥3 ALT/AST/ALP/GGT increase. FINDINGS: Of the 91 included patients, 80 (88%) received prior anti-PD-(L)1. Prior anti-PD-(L)1 and prior immune-related hepatotoxicity were associated with a higher incidence of severe hepatotoxicity (35% versus 0%, p = 0.016 and 75% versus 31%, p = 0.019, respectively). Patients with an interval of ≤6 weeks between anti-PD-(L)1 and sotorasib (n = 18) had a significantly higher incidence of severe hepatotoxicity than those with a 6-12 week (n = 24) and ≥12 week (n = 38) interval (83% versus 33% versus 13%, respectively, p < 0.0001). Sotorasib trough concentrations did not differ significantly between those with or without severe hepatotoxicity (106 versus 126 ng/mL, p = 0.16). Pembrolizumab concentrations were higher in those with severe hepatotoxicity versus those without (25.6 versus 6.1 µg/mL, p < 0.0001). INTERPRETATION: In this preliminary prospective study, sotorasib after PD-(L)1 blockade was associated with severe hepatotoxicity, especially in patients with a short interval between treatments, prior immune-related hepatitis and higher anti-PD-1 plasma concentrations. Our results suggest a minimum interval of 6 weeks between anti-PD-(L)1 and sotorasib to minimize the risk of hepatotoxicity. FUNDING: None.

Impact of COVID-19 on New Graduate Nurses' Transition to Practice: Loss or Gain?

BACKGROUND: The COVID-19 pandemic disrupted nursing education and required modification of instructional methods and clinical experiences. Given the variation in education, rapid transition to virtual platforms, and NCLEX-RN testing stressors, this cohort faced unique losses and gains influencing their transition into clinical practice. PURPOSE: This study examined the impact of COVID-19 and preparedness for professional practice of 340 new graduate nurses (NGNs) at an academic medical center. METHODS: This was a mixed-methods descriptive study focusing on how clinical experience loss or gains in the final semester affected the fears, concerns, and recommendations for NGNs. RESULTS: More than half (67.5%, n = 295) of NGNs reported changes to clinical experiences, ranging from 0 to 240 hours transitioned to virtual (n = 187; median, 51; interquartile range, 24-80). NGNs fear missing important details or doing something wrong in providing patient care. They identified the need for preceptor support, guidance, teaching, and continued practice of skills. CONCLUSION: Recommendations are clear communication with leadership, advocacy from the nurse residency program, and targeted clinical and emotional support for NGNs.