Representativeness of phase III trial for osimertinib in pretreated advanced EGFR-mutated non-small-cell lung cancer patients and treatment outcomes in clinical practice

Background Overall survival (OS) data of osimertinib in pretreated non-small-cell lung cancer (NSCLC) in real-world practice is limited, and treatment benefits for patients not represented in the pivotal trials (ineligible) are unclear. Objective To determine the representativeness of the AURA3 trial for NSCLC patients treated with osimertinib in a real-world setting and to determine outcomes of patients who were represented in the AURA3 trial (eligible) and those who were ineligible. Methods Advanced NSCLC patients receiving post first-line osimertinib were included in this retrospective study and were divided into two groups based on eligibility criteria of the AURA3 trial. Progression-free survival (PFS) and OS were estimated using the Kaplan-Meier method. Cox models were used to estimate the association of eligibility criteria with OS. Results 328 patients were included; 126 (38%) patients were eligible and 202 (62%) patients were ineligible. The most common ineligibility reasons were the number of earlier treatment lines and an Eastern Cooperative Oncology Group performance status (ECOG PS) > 1. PFS of eligible and ineligible patients was not statistically different (8.0 vs. 5.8 months, p = 0.062). Eligible patients had a longer OS (24.0 vs. 15.4 months, p = 0.001) compared to ineligible patients. ECOG PS was the best predictor for OS. An ECOG PS of 1 was already associated with poorer survival compared to an ECOG PS of 0 (hazard ratio 1.54; p = 0.016). Conclusion The majority of the study population was not represented in the AURA3 trial. Survival outcomes of eligible patients are in concordance with the AURA3 trial, while OS of ineligible patients was significantly shorter compared to eligible patients

Competitor phenology as a social cue in breeding site selection

Predicting habitat quality is a major challenge for animals selecting a breeding patch, because it affects reproductive success. Breeding site selection may be based on previous experience, or on social information from the density and success of competitors with an earlier phenology. Variation in animal breeding phenology is often correlated with variation in habitat quality. Generally, animals breed earlier in high-quality habitats that allow them to reach a nutritional threshold required for breeding earlier or avoid nest predation. In addition, habitat quality may affect phenological overlap between species and thereby interspecific competition. Therefore, we hypothesized that competitor breeding phenology can be used as social cue by settling migrants to locate high-quality breeding sites. To test this hypothesis, we experimentally advanced and delayed hatching phenology of two resident tit species on the level of study plots and studied male and female settlement patterns of migratory pied flycatchers Ficedula hypoleuca. The manipulations were assigned at random in two consecutive years, and treatments were swapped between years in sites that were used in both years. In both years, males settled in equal numbers across treatments, but later arriving females avoided pairing with males in delayed phenology plots. Moreover, male pairing probability declined strongly with arrival date on the breeding grounds. Our results demonstrate that competitor phenology may be used to assess habitat quality by settling migrants, but we cannot pinpoint the exact mechanism (e.g. resource quality, predation pressure or competition) that has given rise to this pattern. In addition, we show that opposing selection pressures for arrival timing may give rise to different social information availabilities between sexes. We discuss our findings in the context of climate warming, social information use and the evolution of protandry in migratory animals

Track E Implementation Science, Health Systems and Economics

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138412/1/jia218443.pd