Five-Year Survival Outcomes With Atezolizumab After Chemotherapy in Resected Stage IB-IIIA Non-Small Cell Lung Cancer (IMpower010): An Open-Label, Randomized, Phase III Trial.

IMpower010 (ClinicalTrials.gov identifier: NCT02486718) previously showed that atezolizumab improved disease-free survival (DFS) versus best supportive care (BSC) after adjuvant chemotherapy in patients with resected non-small cell lung cancer (NSCLC). We report DFS final analysis, second overall survival (OS) interim analysis, and safety with a ≥5-year follow-up. Patients with completely resected stage IB-IIIA NSCLC were randomly assigned to atezolizumab (1,200 mg once every 3 weeks, 16 cycles) or BSC after platinum-based chemotherapy. At clinical cutoff (January 26, 2024), stratified hazard ratios (HRs; 95% CI) for DFS were 0.85 (95% CI, 0.71 to 1.01; P = .07) in the intention-to-treat (n = 1,005), 0.83 (95% CI, 0.69 to 1.00) in the all-randomized stage II-IIIA (n = 882), and 0.70 (95% CI, 0.55 to 0.91) in stage II-IIIA PD-L1 tumor cell (TC) ≥1% (n = 476) populations. Stratified HRs (95% CI) for OS were 0.97 (95% CI, 0.78 to 1.22), 0.94 (95% CI, 0.75 to 1.19), and 0.77 (95% CI, 0.56 to 1.06), respectively. The unstratified HRs (95% CI) in the stage II-IIIA PD-L1 TC ≥50% population (n = 229) were 0.48 (95% CI, 0.32 to 0.72) for DFS and 0.47 (95% CI, 0.28 to 0.77) for OS, and the unstratified HRs in the stage II-IIIA PD-L1 TC ≥50% without EGFR/ALK alterations (n = 209) population were 0.49 (95% CI, 0.32 to 0.75) and 0.44 (95% CI, 0.26 to 0.74). No new safety signals were reported. IMpower010 is the first study to report survival outcomes with a ≥5-year follow-up and continued to show benefit with atezolizumab versus BSC after adjuvant chemotherapy in patients with resected stage II-IIIA PD-L1-selected NSCLC

Identification and targeting of regulators of SARS-CoV-2-host interactions in the airway epithelium.

The impact of SARS-CoV-2 in the lung has been extensively studied, yet the molecular regulators of host-cell programs hijacked by the virus in distinct human airway epithelial cell populations remain poorly understood. Some of the reasons include overreliance on transcriptomic profiling and use of nonprimary cell systems. Here we report a network-based analysis of single-cell transcriptomic profiles able to identify master regulator (MR) proteins controlling SARS-CoV-2-mediated reprogramming in pathophysiologically relevant human ciliated, secretory, and basal cells. This underscored chromatin remodeling, endosomal sorting, ubiquitin pathways, as well as proviral factors identified by CRISPR assays as components of the viral-host response in these cells. Large-scale drug perturbation screens revealed 11 candidate drugs able to invert the entire MR signature activated by SARS-CoV-2. Leveraging MR analysis and perturbational profiles of human primary cells represents an innovative approach to investigate pathogen-host interactions in multiple airway conditions for drug prioritization

Differences in door-to-device times in a retrospective cohort of patients with ischemic stroke who received CTA only or CTA and CTP imaging.

Background: In the treatment of acute ischemic stroke, there are differing views about the utility of computerized tomography perfusion (CTP). Two approaches are employed depending on hospital preference. The first approach is to perform non-contrast computed tomography (CT) scans followed by vascular imaging with computed tomography angiography (CTA) for patients arriving within 6 h of last known well. In the first approach, CTP is reserved for patients who arrive 6-24 h after last known well. The second approach is to utilize both CTA and CTP regardless of the time window in which the patient presents. In this study, we sought to answer whether patients triaged with CTP and CTA had increased door-to-device times compared to those only triaged with CTA. Methods: We investigated a retrospective cohort of 1,357 patients with ischemic stroke who received endovascular therapy (EVT) and were triaged with CTA only or CTA and CTP. Patients were stratified by when they arrived at the hospital (\u3c 6 h and 6-24 h from last known well). Linear mixed-effects models (LMM) were used to investigate the association between door-to-device times and CTA/CTP usage. Results: Our results showed that using CTP and CTA was not associated with increased time to treat compared to CTA alone. There was no increase in time from door to device in patients presenting within 6 h. Furthermore, for patients who arrived 6-24 h of last known well, the use of CTP and CTA was associated with an accelerated time to treatment with EVT. Conclusions: CTA and CTP usage was not associated with added time costs with respect to door-to-device in this patient cohort. Our results are consistent with other data showing that radiologists have faster read times when given both CTP and CTA. It is noteworthy that the majority of EVT patients in our dataset (70.6 %) presented in the \u3c 6-hour time window

OVATION-2: A randomized phase I/II study evaluating the safety and efficacy of IMNN-001 (IL-12 gene therapy) with neo/adjuvant chemotherapy in patients newly-diagnosed with advanced epithelial ovarian cancer.

OBJECTIVE: OVATION-2, a randomized, controlled, open label phase 1/2 study, evaluated the safety and efficacy of IMNN-001, an IL-12 immune gene therapy, with neo/adjuvant chemotherapy (N/ACT) compared to N/ACT in newly-diagnosed advanced epithelial ovarian cancer (EOC). METHODS: IMNN-001 is an immunotherapeutic nanoparticle comprising a DNA plasmid encoding the IL-12 gene encased in a lipopolymer. High-grade EOC patients were randomized 1:1 to carboplatin/paclitaxel IV every 21 days for 3 cycles, before and after interval debulking surgery (IDS) or to intraperitoneal (IP) IMNN-001, given weekly concurrently with chemotherapy for 8 weeks before and 9 weeks after IDS. RESULTS: 54 and 58 patients with predominantly Stage IIIC/IV EOC were evaluated in the control and experimental arm, respectively. Primary endpoints were safety and PFS. Overall, the experimental arm was well tolerated with gastrointestinal and cytopenias as the most common TEAEs with no CRS or elevated risk of immune events. PFS was 14.9 months (mo) for the experimental arm vs 11.9 mo; HR 0.79 (95 % CI: 0.51-1.23). Secondary endpoints included OS (46.0 mo for experimental arm vs 33.0 mo; HR 0.69 (CI: 0.40-1.19)) and surgical response R0 rate (64.6 % experimental arm vs 52.1 %). For patients who received PARPi maintenance, PFS was 33.8 mo vs 22.1 mo; HR 0.80 (CI: 0.31-2.12) and OS was NE vs 37.1 mo with a HR of 0.38 (CI: 0.13-1.06) both favoring the experimental arm. CONCLUSION: The addition of IMNN-001 to N/ACT shows a promising numerical 13-mo benefit on survival with an acceptable safety profile in patients with newly-diagnosed advanced EOC

Molecular Correlates of Long-Term Response to Bevacizumab in Glioblastoma.

Purpose: The use of bevacizumab in glioblastoma has been associated with increased progression-free survival and improvement in symptoms and quality of life. There are no clinical indicators on how to choose patients who would benefit the most from this agent. We aim to describe molecular markers in patients with glioblastoma who may benefit from treatment. Methods: We analyzed glioblastoma tumor samples that underwent comprehensive molecular profiling analysis at Caris Life Sciences. Results: The data set consisted of 3,106 glioblastoma tumor samples, of which 571 were from patients treated with bevacizumab. The majority were males (65%) and older than 60 years. Median survival was 17.5 months in patients receiving bevacizumab. In patients who were treated with bevacizumab for ≥1 year, median survival was 33.8 months, compared with 15 months in those treated for ≤6 months. Patients who received bevacizumab for ≥1 year had higher prevalence of LRIG3 (9% v 1%), CDK4 (22% v 8%), and DDIT3 amplification (14% v 4%), SETD2 mutations (10% v 3%), and MGMT methylation (66% v 32%). EGFR amplification was more frequent in patients who received bevacizumab for ≤6 months (46% v 20%). Multivariate analysis showed that CDK4 amplification was associated with longer time on bevacizumab, and EGFR amplification with shorter time after correcting for age, sex, and other molecular alterations. Conclusion: CDK4 amplification is a potential genetic biomarker to identify patients who may derive prolonged benefit from bevacizumab

Comparative Analysis of Injury and Illness Rates Among Team USA Athletes at the Tokyo 2020 Summer Olympic and Paralympic Games.

BACKGROUND: Previous research has reported higher rates of both injury and illness among Paralympic athletes compared with Olympic athletes during the Winter Olympic and Paralympic Games, but no studies have directly compared injury and illness incidence between Olympic and Paralympic athletes competing in a Summer Games. PURPOSE: To compare injury and illness rates between Olympic and Paralympic Team USA athletes competing in the Tokyo 2020 Olympic and Paralympic Games. STUDY DESIGN: Descriptive epidemiology study. METHODS: All injuries and illnesses that occurred among the Team USA athletes competing in the Tokyo 2020 Summer Olympic or Paralympic Games were documented. A total of 701 Team USA athletes (53.6% female) competed in the Tokyo 2020 Summer Olympic Games, across 34 different sports. For the Tokyo 2020 Summer Paralympic Games, a total of 245 athletes (51.6% female) competed across 20 sports. Incidence rates (IRs) per 1000 athlete-days were calculated according to sex, sport, anatomic location, and illness type. IR ratios (IRRs) were calculated to compare IRs between male and female athletes and between Olympic and Paralympic athletes. RESULTS: Overall, there were no differences in injury incidence (IRR, 1.18; 95% CI, 0.84-1.68) or illness incidence (IRR, 0.68; 95% CI, 0.41-1.15) between Olympic and Paralympic athletes. Male Paralympic athletes were less likely to sustain an illness compared with female Paralympic athletes (IRR, 0.35; 95% CI, 0.11-0.90). CONCLUSION: There were no differences in injury or illness rates between Olympic and Paralympic Team USA athletes competing at the Tokyo 2020 Summer Games, contrary to previous comparisons among winter sport athletes. These results challenge the prevailing notion that Summer Paralympic athletes are at greater injury and illness risk, suggesting that factors beyond Olympic or Paralympic Games participation influence health concerns