PURPOSE: To assess the relationship among tumor response rate, overall survival, and the development of related adverse events of special interest (AESIs) or related immune-mediated adverse events (imAEs) in patients with urothelial cancer treated with anti–programmed death protein 1 or ligand 1 (anti–PD-1/L1) antibodies. PATIENTS AND METHODS: We examined seven trials in 1,747 patients with metastatic or locally advanced urothelial cancer that led to approval of an anti–PD-1/L1 antibody. Five trials enrolled patients who had received prior platinum-based therapy, and two enrolled patients who were cisplatin ineligible. The data sets were searched for AESIs, related AESIs, imAEs, and related imAEs. The relationship to study drug was determined by the investigator. ImAEs were defined as AESIs treated with topical or systemic corticosteroids. RESULTS: In these exploratory analyses, a related AESI was reported in 64% of responding patients and in 34% of patients who did not respond to the anti–PD-1/L1 antibody, whereas a related imAE occurred in 28% and 12% of patients who did and did not respond to study drug, respectively. In a responder analysis, an increase in overall survival was seen in patients with related AESIs compared with those with no related AESIs (hazard ratio, 0.45; 95% CI, 0.39 to 0.52). Fifty-seven percent of responding patients with a related AESI reported the AESI before documentation of response. CONCLUSION: Patients who responded to treatment with an anti–PD-1/L1 antibody were more likely to report a related AESI or related imAE. This relationship did not seem to be due to the increased duration of exposure in responding patients. Systemic corticosteroid use did not appear to affect the duration of response.

The Indian Council of Medical Research, in 2013, initiated the Antimicrobial Resistance Surveillance & Research Network (AMRSN) to enable compilation of data on six pathogenic groups on antimicrobial resistance from the country. The overarching aim of this network was to understand the extent and pattern of antimicrobial resistance (AMR) and use this evidence to guide strategies to control the spread of AMR. This article describes the conception and implementation of this AMR surveillance network for India. Also described are the challenges, limitations and benefits of this approach. Data from the Network have shown increasing resistance in Gram-negative bacteria in the hospitals that are part of this network. Combined resistance to third-generation cephalosporins and fluoroquinolones and increasing carbapenem resistance are worrisome, as it has an important bearing on the patients’ outcome and thus needs to be addressed urgently. Data generated through this Network have been used to develop treatment guidelines, which will be supportive in harmonizing treatment practices across the tertiary level healthcare institutions in the country. While, the major benefit of having a surveillance system is the collection of real-time accurate data on AMR including the mechanisms of resistance, representativeness to community, sustaining the current effort and expanding the current activities to next levels of healthcare settings are the major challenges. The data emanating from the network besides providing evidence, expose several gaps and lacunae in the ecosystem and highlight opportunities for action by multiple stakeholders.

On July 17, 2017, the FDA approved neratinib (NERLYNX; Puma Biotechnology, Inc.) for the extended adjuvant treatment of adult patients with early-stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy. Approval was based on data from ExteNET, a randomized, double-blind, placebo-controlled multicenter trial. Women with early-stage HER2-positive breast cancer and within 2 years of completing adjuvant trastuzumab were randomized to neratinib (n = 1,420) or placebo (n = 1,420) for 1 year. The primary endpoint was invasive disease-free survival (iDFS), defined as the time between randomization date to first occurrence of invasive recurrence (local/regional, ipsilateral, or contralateral breast cancer), distant recurrence, or death from any cause, with 2 years and 28 days of follow-up. The trial showed a statistically significant treatment effect favoring neratinib with a stratified HR of 0.66 [95% confidence interval (CI), 0.49–0.90, P = 0.008]. The estimated iDFS rate at 2 years was 94.2% (95% CI, 92.6%–95.4%) in patients treated with neratinib versus 91.9% (95% CI, 90.2%–93.2%) in those receiving placebo. Diarrhea was the most common adverse event (AE), with a 40% incidence of grade 3 or 4 diarrhea, and represents the most common AE leading to treatment discontinuation. Other frequent AEs (>10% incidence) were nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, and muscle spasms. Other than diarrhea, neratinib is associated with a low incidence of severe AEs; toxicities are generally reversible and manageable with dose interruptions, dose reductions, and/or standard medical care. This article summarizes FDA decision-making and data supporting the neratinib approval. Clin Cancer Res; 24(15); 3486–91. ©2018 AACR. See related commentary by Unni et al., p. 3483

The full extent of global smokeless tobacco (SLT) use and its association with key demographic factors such as gender, place of residence, and household or country income status is not yet known. The global burden of SLT use among adults was estimated using nationally representative data of 140 countries by gender and country income group. Countries were grouped in Group 1 (low and low-middle income countries combined) and Group 2 (upper middle and high income countries combined). The number of male and female SLT users was calculated using prevalence and population estimates of corresponding age groups. Nearly one in 10 males and one in 20 females used SLT in some form. SLT use prevalence was significantly higher among males (p < .001) and females (p < .001) in Group 1 countries compared with their counterparts in Group 2 countries. However, for both Group 1 (p < .01) and Group 2 (p < .01), males were more likely to use SLT than females. Nearly 91% of a total 356 million adult SLT users resided in Group 1 countries, with 81.6% in countries of WHO South-East Asia region (SEAR). In SEAR and African region, SLT use was higher in rural areas and poorest communities. The majority of the burden of SLT use is on lower and lower middle income countries with the greatest burden on the poorest segments of the population in these countries. This study brings the comprehensive information on epidemiology of SLT use among adults at global level. Ninety percent of SLT burden is in low and low-middle income group of countries and more specifically among the poorest group in such countries. These countries need to have strategies to implement different provisions of the WHO Framework Convention on Tobacco Control. The program in such countries should be targeted towards the poorest communities for effective SLT control.