Osimertinib benefit in EGFR-mutant NSCLC patients with T790M-mutation detected by circulating tumour DNA

BACKGROUND: Approximately 50% of Epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (TKIs) will acquire resistance by the T790M mutation. Osimertinib is the standard of care in this situation. The present study assesses the efficacy of osimertinib when T790M status is determined in circulating cell-free tumour DNA (ctDNA) from blood samples in progressing advanced EGFR-mutant NSCLC patients. MATERIAL AND METHODS: ctDNA T790M mutational status was assessed by Inivata InVision(TM) (eTAm-Seq(TM)) assay in 48 EGFR-mutant advanced NSCLC patients with acquired resistance to EGFR TKIs without a tissue biopsy between April 2015 and April 2016. Progressing T790M-positive NSCLC patients received osimertinib (80 mg daily). The objectives were to assess the response rate to osimertinib according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, the progression-free survival (PFS) on osimertinib, and the percentage of T790M positive in ctDNA. RESULTS: The ctDNA T790M mutation was detected in 50% of NSCLC patients. Among evaluable patients osimertinib gave a partial response rate of 62.5% and a stable disease rate of 37.5%. All responses were confirmed responses. After median follow up of 8 months, median PFS by RECIST criteria was not achieved (95% CI: 4-NA), with 6- and 12-months PFS of 66.7% and 52%, respectively. CONCLUSIONS: ctDNA from liquid biopsy can be used as a surrogate marker for T790M in tumour tissue

Peripatetic health-care workers as potential superspreaders

Many nosocomial outbreaks exhibit “superspreading events” in which cross-transmission occurs via a single individual to a large number of patients. We investigated how heterogeneity in Health-Care Worker (HCW) behaviors, especially compliance to hand hygiene, may cause superspreading events. In particular, we compared the superspreading potential of peripatetic (noncohorted) HCWs with that of other HCWs. We developed an agent-based model for hand transmission of a pathogen in a hospital ward. Three HCW profiles were allowed: 2 assigned profiles, one with frequent contacts with a limited number of patients, another with fewer contacts but with more patients; and one peripatetic profile, with a single daily contact with all patients. We used data from the literature on common nosocomial pathogens (Staphylococcus aureus, Enterococci). The average number of patients colonized over 1 month increases with noncompliance to hand hygiene. Importantly, we show that this increase depends on the profile of noncompliant HCWs; for instance, it remains low for a single noncompliant assigned HCW but can be quite large for a single noncompliant peripatetic HCW. Outbreaks with this single fully noncompliant peripatetic HCW (representing only 4.5% of the staff) are similar to those predicted when all HCWs are noncompliant following 23% of patient contacts. Noncompliant peripatetic HCWs may play a disproportionate role in disseminating pathogens in a hospital ward. Their unique profile makes them potential superspreaders. This suggests that average compliance to hygiene may not be a good indicator of nosocomial risk in real life health care settings with several HCW profiles