Updated Efficacy Analysis Including Secondary Population Results for OAK: A Randomized Phase III Study of Atezolizumab versus Docetaxel in Patients with Previously Treated Advanced Non-Small Cell Lung Cancer.

INTRODUCTION: The efficacy and safety of atezolizumab versus the efficacy and safety of docetaxel as second- or third-line treatment in patients with advanced NSCLC in the primary (n = 850) and secondary (n = 1225) efficacy populations of the randomized phase III OAK study (respectively referred to as the intention-to-treat [ITT] 850 [ITT850] and ITT1225) at an updated data cutoff were assessed. METHODS: Patients received atezolizumab, 1200 mg, or docetaxel, 75 mg/m2, intravenously every 3 weeks until loss of clinical benefit or disease progression, respectively. The primary end point was overall survival (OS) in the ITT population and programmed death-ligand 1-expressing subgroup. A sensitivity analysis was conducted to evaluate the impact of subsequent immunotherapy use in the docetaxel arm on the observed survival benefit with atezolizumab. RESULTS: Atezolizumab demonstrated an OS benefit versus docetaxel in the updated ITT850 (hazard ratio [HR] = 0.75, 95% confidence interval: 0.64-0.89, p = 0.0006) and the ITT1225 (HR = 0.80, 95% confidence interval: 0.70-0.92, p = 0.0012) after minimum follow-up times of 26 and 21 months, respectively. Improved survival with atezolizumab was observed across programmed death-ligand 1 and histological subgroups. In the immunotherapy sensitivity analysis, the relative OS benefit with atezolizumab was slightly greater in the ITT850 (HR = 0.69) and ITT1225 (HR = 0.74) than the conventional OS estimate. Fewer patients receiving atezolizumab experienced grade 3 or 4 treatment-related adverse events (14.9%) than did patients receiving docetaxel (42.4%); no grade 5 adverse events related to atezolizumab were observed. CONCLUSIONS: The results of the updated ITT850 and initial ITT1225 analyses were consistent with those of the primary efficacy analysis demonstrating survival benefit with atezolizumab versus with docetaxel. Atezolizumab continued to demonstrate a favorable safety profile after longer treatment exposure and follow-up.

Virulence of Corynosoma constrictum (Acanthocephala: Polymorphidae) in Hyalella azteca (Amphipoda) throughout parasite ontogeny.

Development and growth of parasites depend on resources provided by the host and the parasite's ability to use them. Identifying specific costs incurred by the host provides insight for assessment of parasite energy budgets, which differ among taxa and ontogenetic stages. Data from this study were analyzed using an accelerated failure-time model with intensity as a covariate. Results indicated significantly reduced survival of amphipods, Hyalella azteca, infected with the acanthocephalan Corynosoma constrictum compared with uninfected controls. Male and female amphipod survivorship and infection intensity did not differ; however, amphipods with high-intensity infections (> 16 larvae) died earlier compared with amphipods with low-intensity infections (< 3 larvae). The majority of infected amphipods died between 12 and 24 days postexposure, a period of rapid larval development. It is hypothesized that host death may be due either to an increase in overall larval nutritional demands or to parasite-mediated depletion of a specific host substance. Results from this study suggest that developing C. constrictum satisfies energy requirements by depriving amphipod hosts of resources normally used for somatic growth and maintenance.

Resource-mediated impact of spider predation risk on performance in the grasshopper Ageneotettix deorum (Orthoptera: Acrididae).

In response to increased exposure to predators when searching for food, many prey increase the frequency of antipredator behaviors, potentially reducing foraging rate and food intake. Such direct, nonlethal interactions between predators and prey resulting in reduced food intake can indirectly influence lifecycle development through effects on growth, developmental rate, and survival. We investigated the general hypothesis that individual performance of a herbivorous insect can be negatively affected when exposed to nonlethal predation risk, and that the response can be mediated by food quality. This hypothesis was tested using the common rangeland grasshopper Ageneotettix deorum with and without exposure to common wolf spider predators (Lycosidae, Schizocosa spp.) on both untreated natural and fertilized vegetation. All spiders were rendered temporarily incapable of direct feeding by restricting function of the chelicerae with beeswax. Detectable responses by grasshoppers to spiders indicate indirect consequences for lifecycle development. Grasshopper performance was measured as hind femur growth, duration of nymphal lifecycle stages, and survivorship in a caged field experiment conducted over 2 years. Grasshoppers developed faster and grew 3-5% larger when allowed to forage on fertilized vegetation in the absence of risk from a spider predator. Failure-time analysis illustrated enhanced survival probability in response to elevated food quality and the negative effects of grasshopper susceptibility to nonlethal predation risk. Performance on food of relatively low, ambient quality with no predation risk equaled that of grasshoppers caged with high quality vegetation in the presence of a modified spider. Increased resource quality can clearly moderate the negative life history responses caused by the behavioral modification of grasshoppers when exposed to spider predation risk, a compensatory response.