Overall Survival From the EORTC LCG-1613 APPLE Trial of Osimertinib Versus Gefitinib Followed by Osimertinib in Advanced EGFR-Mutant Non-Small-Cell Lung Cancer.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Osimertinib has been established as a standard of care for patients with common sensitizing EGFR-mutant advanced non-small-cell lung cancer (NSCLC) although the sequential approach (first-generation inhibitor gefitinib followed by osimertinib) has not been formally compared. The phase II APPLE trial (ClinicalTrials.gov identifier: NCT02856893) enrolled 156 treatment-naïve patients, and two treatment strategies were evaluated: osimertinib up front or the sequential treatment approach with gefitinib up front followed by osimertinib at the time of progression, either molecular progression (detection of plasma T790M resistance mutation) regardless of the radiologic status or just at the time of radiologic progression. Patients' characteristics were well balanced, except for the higher proportion of baseline brain metastases in the sequential approach (29% v 19%). Per protocol, 73% of patients switched to osimertinib in the sequential arm. Up-front treatment with osimertinib was associated with a lower risk of brain progression versus the sequential approach (hazard ratio [HR], 0.54 [90% CI, 0.34 to 0.86]), but a comparable overall survival was observed between both strategies (HR, 1.01 [90% CI, 0.61 to 1.68]), with the 18-month survival probability of 84% and 82.3%, respectively. The APPLE trial suggests that a sequential treatment approach is associated with more frequent progression in the brain but a similar survival in advanced EGFR-mutant NSCLC.

Microbiome features associated with performance measures in athletic and non-athletic individuals: A case-control study.

The influence of human gut microbiota on health and disease is now commonly appreciated. Therefore, it is not surprising that microbiome research has found interest in the sports community, hoping to improve health and optimize performance. Comparative studies found new species or pathways that were more enriched in elites than sedentary controls. In addition, sport-specific and performance-level-specific microbiome features have been identified. However, the results remain inconclusive and indicate the need for further assessment. In this case-control study, we tested two athletic populations (i.e. strength athletes, endurance athletes) and a non-athletic, but physically active, control group across two acute exercise bouts, separated by a 2-week period, that measured explosive and high intensity fitness level (repeated 30-s all-out Wingate test (WT)) and cardiorespiratory fitness level (Bruce Treadmill Test). While we did not identify any group differences in alpha and beta diversity or significant differential abundance of microbiome components at baseline, one-third of the species identified were unique to each group. Longitudinal sample (pre- and post-exercise) analysis revealed an abundance of Alistipes communis in the strength group during the WT and 88 species with notable between-group differences during the Bruce Test. SparCC recognized Bifidobacterium longum and Bifidobacterium adolescentis, short-chain fatty acid producers with probiotic properties, species strongly associated with VO2max. Ultimately, we identified several taxa with different baseline abundances and longitudinal changes when comparing individuals based on their VO2max, average power, and maximal power parameters. Our results confirmed that the health status of individuals are consistent with assumptions about microbiome health. Furthermore, our findings indicate that microbiome features are associated with better performance previously identified in elite athletes.