Introduction:The efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in EGFR mutation-positive non–small-cell lung cancer (NSCLC) patients necessitates accurate, timely testing. Although EGFR mutation testing has been adopted by many laboratories in Asia, data are lacking on the proportion of NSCLC patients tested in each country, and the most commonly used testing methods.Methods:A retrospective survey of records from NSCLC patients tested for EGFR mutations during 2011 was conducted in 11 Asian Pacific countries at 40 sites that routinely performed EGFR mutation testing during that period. Patient records were used to complete an online questionnaire at each site.Results:Of the 22,193 NSCLC patient records surveyed, 31.8% (95% confidence interval: 31.2%–32.5%) were tested for EGFR mutations. The rate of EGFR mutation positivity was 39.6% among the 10,687 cases tested. The majority of samples were biopsy and/or cytology samples (71.4%). DNA sequencing was the most commonly used testing method accounting for 40% and 32.5% of tissue and cytology samples, respectively. A pathology report was available only to 60.0% of the sites, and 47.5% were not members of a Quality Assurance Scheme.Conclusions:In 2011, EGFR mutation testing practices varied widely across Asia. These data provide a reference platform from which to improve the molecular diagnosis of NSCLC, and EGFR mutation testing in particular, in Asia.

Introduction: Using real-world Japanese postmarketing data, we characterized interstitial lung disease (ILD) development during the second-or later-line osimertinib treatment for EGFR mutation-positive NSCLC. Retrospective radiologic image evaluation of patients developing ILD was also performed.Methods: Patients who had ILD events reported as an adverse drug reaction by their physicians and who were assessed as having developed ILD as assessed by an ILD expert committee in Japan were included.Results: Among 3578 patients, 252 ILD events were reported in 245 patients (6.8%) by their attending physicians. The median (range) time to the first onset of ILD after

Objective Adverse drug reactions (ADRs) during real-world osimertinib use were investigated in Japan. Methods Patients with epidermal growth factor receptor (EGFR) T790M-positive non-small cell lung cancer treated with second-line or later oral osimertinib per the Japanese package insert (80 mg once daily) were included. Data were collected between 28 March 2016 and 31 August 2018. Results The median observation period in the safety analysis population (n = 3578) was 343.0 days. ADRs (defined as adverse events whose causality to osimertinib could not be denied by the attending physicians or manufacturer) were reported in 58.1% (2079/3578) of patients. ADRs of interstitial lung disease events were reported in 6.8% (245/3578; Grade ≥ 3, 2.9% [104/3578]) of patients, of whom 29 (11.8%) died (0.8% of patients overall). ADRs of QT interval prolonged, liver disorder and haematotoxicity were reported in 1.3% (45/3578; Grade ≥ 3, 0.1% [5/3578]), 5.9% (212/3578; Grade ≥ 3, 1.0% [35/3578]) and 11.4% (409/3578; Grade ≥ 3, 2.9% [104/3578]) of patients, respectively. In the efficacy analysis population (n = 3563), 119 (3.3%) patients had complete responses, 2373 (66.6%) had partial responses and 598 (16.8%) had stable disease. The objective response rate was 69.9%; disease control rate was 86.7%; and median progression-free survival (PFS) was 12.3 months. At 6 and 12 months, PFS rates were 77.4% (95% confidence interval [CI], 75.9–78.9) and 53.2% (95% CI, 51.3–55.1) and overall survival rates were 88.3% (95% CI, 87.2–89.4) and 75.4% (95% CI, 73.8–77.0), respectively. Conclusions These data support the currently established benefit-risk assessment of osimertinib in this patient population.

The maximum annual reproductive rate (i.e., the slope at the origin in a stock-recruitment relationship) is one of the most important biological reference points in fisheries; it sets the upper limit to sustainable fishing mortality. Estimating the maximum reproductive rate by fitting parametric models to stock-recruitment data may not be a robust approach because two statistically indistinguishable models can generate radically different estimates. To mitigate this issue, we developed a flexible, semiparametric Bayesian approach based on a conditional Gaussian process prior specifically designed to estimate the maximum annual reproductive rate, and applied it to analyze simulated stock-recruitment data sets. Compared with results based on other Gaussian process priors, we found that the conditional Gaussian process prior provided superior results: the accuracy and precision of estimates were enhanced without increasing model complexity. Moreover, compared with parametric alternatives, performance of the conditional Gaussian process prior was comparable to that of the data-generating model and always better than the wrong model.

The importance of Allee effects has long been recognized both in theoretical studies of population dynamics and in conservation sciences. Although the necessary conditions for Allee effects to occur (e.g., difficulty in finding mates and mortality driven by generalist predators at low density) would seem to apply to many species, evidence for Allee effects in natural populations is equivocal at best. This apparent scarcity might be an artifact driven by poor power to detect them with traditional parametric models. To circumvent this potential problem, we developed a semiparametric Bayesian method based on a Gaussian process prior. We validated the method using simulated data sets and applied it to three herring data sets.