Entrectinib in ROS1-positive advanced non-small cell lung cancer: the phase 2/3 BFAST trial.

Although comprehensive biomarker testing is recommended for all patients with advanced/metastatic non-small cell lung cancer (NSCLC) before initiation of first-line treatment, tissue availability can limit testing. Genomic testing in liquid biopsies can be utilized to overcome the inherent limitations of tissue sampling and identify the most appropriate biomarker-informed treatment option for patients. The Blood First Assay Screening Trial is a global, open-label, multicohort trial that evaluates the efficacy and safety of multiple therapies in patients with advanced/metastatic NSCLC and targetable alterations identified by liquid biopsy. We present data from Cohort D (ROS1-positive). Patients ≥18 years of age with stage IIIB/IV, ROS1-positive NSCLC detected by liquid biopsies received entrectinib 600 mg daily. At data cutoff (November 2021), 55 patients were enrolled and 54 had measurable disease. Cohort D met its primary endpoint: the confirmed objective response rate (ORR) by investigator was 81.5%, which was consistent with the ORR from the integrated analysis of entrectinib (investigator-assessed ORR, 73.4%; data cutoff May 2019, ≥12 months of follow-up). The safety profile of entrectinib was consistent with previous reports. These results demonstrate consistency with those from the integrated analysis of entrectinib in patients with ROS1-positive NSCLC identified by tissue-based testing, and support the clinical value of liquid biopsies to inform clinical decision-making. The integration of liquid biopsies into clinical practice provides patients with a less invasive diagnostic method than tissue-based testing and has faster turnaround times that may expedite the reaching of clinical decisions in the advanced/metastatic NSCLC setting. ClinicalTrials.gov registration: NCT03178552 .

High-dose alectinib for RET fusion-positive non-small cell lung cancer in the Blood First Assay Screening Trial.

Introduction: This paper presents results from Cohort B (rearranged during transfection [RET], fusion-positive) of the Blood First Assay Screening Trial in patients with advanced non-small cell lung cancer (NSCLC) screened for genetic alterations using blood-based next-generation sequencing. Material and methods: Adults with advanced RET fusion-positive NSCLC received alectinib 900 mg twice daily (BID) in Phase I. Enrolment closed prematurely with Phase II uninitiated. Results: Among eight treated patients, confirmed best overall responses in evaluable patients were stable disease (4/5) and progressive disease (1/5). One dose-limiting toxicity (death, unknown cause) was considered by the investigator to be related to treatment and underlying disease. Serious adverse events (SAEs) occurred in five patients, and SAEs that may be related to treatment occurred in two patients. Conclusions: Alectinib showed limited activity in advanced RET fusion-positive NSCLC, and further investigation was not conducted due to the development of selective RET inhibitors pralsetinib and selpercatinib. No new safety signals were observed, and the safety profile of alectinib was in line with previous reports at the 600 mg BID dose.

Increasing reliability of APACHE II scores in a medical-surgical intensive care unit: a quality improvement study.

BACKGROUND: Given their clinical, research, and administrative purposes, scores on the Acute Physiology and Chronic Health Evaluation (APACHE) II should be reliable, whether calculated by health care personnel or a clinical information system. OBJECTIVE: To determine reliability of APACHE II scores calculated by a clinical information system and by health care personnel before and after a multifaceted quality improvement intervention. METHODS: APACHE II scores of 37 consecutive patients admitted to a closed, 15-bed, university-affiliated intensive care unit were collected by a research coordinator, a database clerk, and a clinical information system. After a quality improvement intervention focused on health care personnel and the clinical information system, the same methods were used to collect data on 32 consecutive patients. The research coordinator and the clerk did not know each other's scores or the information system's score. The data analyst did not know the source of the scores until analysis was complete. RESULTS: APACHE II scores obtained by the clerk and the research coordinator were highly reliable (intraclass correlation coefficient, 0.88 before vs 0.80 after intervention; P = .25). No significant changes were detected after the intervention; however, compared with scores of the research coordinator, the overall reliability of APACHE II scores calculated by the clinical information system improved (intraclass correlation coefficient, 0.24 before intervention vs 0.91 after intervention, P < .001). CONCLUSIONS: After completion of a quality improvement intervention, health care personnel and a computerized clinical information system calculated sufficiently reliable APACHE II scores for clinical, research, and administrative purposes.