Real-World Outcomes With Lurbinectedin in Second-Line Setting and Beyond for Extensive Stage Small Cell Lung Cancer.

BACKGROUND: Lurbinectedin has emerged as a potential treatment option for relapsed small cell lung cancer (SCLC). While clinical trials have demonstrated its efficacy and safety, real-world data are limited. This study aimed to evaluate the safety and efficacy of lurbinectedin in a real-world setting, focusing on its use as a second-line agent and beyond in SCLC patients. METHODS: A retrospective analysis was conducted on 90 patients who received lurbinectedin between June 2020 and June 2022 within the Mayo Clinic Health System. Of these, 50 patients received lurbinectedin as a second-line agent, and 14 patients received it as a third-line or later agent. The primary outcomes assessed were overall survival (OS), progression-free survival (PFS), and treatment-related adverse events. RESULTS: Lurbinectedin was generally well tolerated in this real-world cohort, with a median OS of 5.1 months in the second-line cohort and 5.6 months in the third-line or later cohort. Median PFS was 2.1 months in the second-line cohort and 3.4 months in the third-line or later cohort. Adverse events were manageable, with the most common being neutropenia, anemia, fatigue, and febrile neutropenia. No treatment-related deaths or grade 5 toxicities were reported. CONCLUSION: This real-world study provides valuable insights into the safety and efficacy of lurbinectedin in relapsed SCLC. Lurbinectedin demonstrated modest efficacy and a comparable safety profile to that observed in clinical trials. However, outcomes for relapsed SCLC remain suboptimal, particularly for patients with a shorter chemotherapy-free interval and central nervous system metastases.

Time from immune checkpoint inhibitor to sotorasib use correlates with risk of hepatotoxicity in non-small cell lung cancer: A brief report.

INTRODUCTION: We evaluated the risk factors and outcomes for patients who experienced hepatotoxicity after use of sotorasib in KRAS G12C mutated NSCLC. METHODS: Retrospective review of medical records of patients with KRAS G12C mutated NSCLC who received sotorasib between May 28th, 2021, and December 31st, 2021 across all Mayo Clinic sites, with follow up until December 31st, 2022. RESULTS: Thirty-one patients received sotorasib as standard of care treatment. Grade 3 or higher hepatoxicity was seen in 32% (10/31) patients presenting at a median of 51 days (range, 27-123) of sotorasib initiation. Baseline demographics were comparable between patients with and without ≥grade 3 hepatotoxicity, except for presence of CNS metastases and time from prior immune checkpoint inhibitor (ICI) treatment. Improvement in liver tests was observed in all patients after stopping sotorasib, and it was restarted at a lower dose in 8 patients. Despite dose reduction, hepatotoxicity requiring sotorasib discontinuation occurred in 2 patients. Twenty-eight of 31 patients had received prior ICI. Median time from prior ICI therapy was 69 days (range, 4-542). Rates of ≥grade 3 hepatoxicity were 75% (3/4), 64% (7/11) and 0% (0/13) for patients who received ICI within 30 days, 31-90 days and >90 days. None of the 3 patients without prior ICI exposure developed hepatoxicity. The median PFS and OS were 3.9 months and 9.9 months respectively. CONCLUSION: One-third of patients developed grade 3 or higher sotorasib induced hepatotoxicity. Risk of hepatotoxicity was higher in patients who received sotorasib within 90 days of ICI treatment.

Total Red Blood Cell Transfusions for Chronic Hemodialysis Patients in a Single Center, 2009-2013.

BACKGROUND: Anemia management in chronic hemodialysis (HD) has been affected by the implementation of the prospective payment system (PPS) and changes in clinical guidelines. These factors could impact red blood cell (RBC) transfusion in HD patients. Our distinctive care system contains complete records for all RBC transfusions among our HD patients. AIMS: To determine RBC transfusions in patients with prevalent chronic HD, site of administration (inpatient or outpatient), and ordering physician specialty for inpatients; compare pre- and post-PPS RBC transfusions; and compare RBC transfusions during changes in desired outpatient hemoglobin (Hb) range for patients with chronic HD. METHODS: Retrospective analysis of medical and blood bank records for patients with prevalent chronic HD July 2009 through June 2013. RESULTS: In total, 310-356 patients were studied. Mean (SD) units of RBCs per 100 patients per month for the study's 48 months were outpatient, 2.6 (1.5), and inpatient, 9.4 (4.6). Outpatient pre-PPS RBC units transfused were 2.1 (0.6) vs. post-PPS of 2.6 (1.5; p = 0.22, t test); for inpatients pre-PPS, 7.9 (4.5) RBC units per month vs. post-PPS, 11.5 (5.1; p = 0.11, t test). Inpatient RBC transfusions accounted for 75.2% (14.2%) of all RBC transfusions; 67.3% (16.3%) of inpatient transfusions were ordered by nonnephrologists. Changes in desired Hb range for outpatient HD patients did not lead to changes in RBC transfusions. CONCLUSIONS: No changes in RBC transfusions occurred among our patients with chronic HD with PPS implementation and in desired Hb range during the study period. Most transfusions were given in inpatient settings by nonnephrologists.

Biomedical system dynamics to improve anemia control with darbepoetin alfa in long-term hemodialysis patients.

OBJECTIVE: To determine the value of a biomedical system dynamics (BMSD) approach for optimization of anemia management in long-term hemodialysis patients because elevated hemoglobin levels and high doses of erythropoiesis-stimulating agents (ESAs) may negatively affect survival in this population. PATIENTS AND METHODS: A model of erythropoiesis and its response to ESAs on the basis of a BMSD method (Mayo Clinic Anemia Management System [MCAMS]) was developed. Thereafter, an open-label, prospective, nonrandomized practice quality improvement project was performed with retrospective analysis in 8 community-based outpatient hemodialysis facilities. All prevalent hemodialysis patients seen from January 1, 2007, through December 31, 2010 (300-342 patients per month), were included with darbepoetin as the ESA. The primary outcome was the percentage of patients who attained the desired hemoglobin level. Secondary outcome measures included the percentage of patients with hemoglobin values above the desired range and mean dose of darbepoetin used. RESULTS: The 3 treatment periods were (1) standard ESA protocol in 2007, (2) transition to the MCAMS (2008 to June 2009), and (3) stability period with the MCAMS used in all hemodialysis facilities (2009 to 2010). In the first 6 months of 2007, 69% of patients were in the desired range and 26% were above the range. In comparison, during the first 5 months of 2010, 83% were in and 6% were above the range (P<.001). The mean monthly darbepoetin dose per patient decreased from 304 µg in 2007 to 173 µg by the second half of 2009 (P<.001). CONCLUSION: With the introduction of the MCAMS, more patients had hemoglobin levels in the desired range and fewer patients exceeded the target range, with a concomitant 40% reduction in darbepoetin use.