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Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) have an established role in the treatment of non-small-cell lung cancer (NSCLC). First-generation reversible ATP-competitive EGFR-TKIs are approved for the initial treatment of patients with EGFR mutation-positive advanced NSCLC. Afatinib is an irreversible second-generation EGFR-TKI with potent preclinical activity against EGFR (wild type and mutant), HER2, HER4 and EGFR-mutant NSCLC with acquired resistance to reversible EGFR-TKI. LUX-Lung 3 trial demonstrated superiority of afatinib to cisplatin and pemetrexed in the frontline treatment of treatment-naïve patients with advanced adenocarcinoma of the lung and EGFR mutation. Based on these results, afatinib was recently approved for the first-line treatment of NSCLC patients with EGFR mutation. This article summarizes current status of preclinical and clinical development of afatinib in NSCLC.

Heat waves in India during the pre-monsoon months have significant impacts on human health, productivity and mortality. While greenhouse gas-induced global warming is believed to accentuate high temperature extremes, anthropogenic aerosols predominantly constituted by radiation-scattering sulfate are believed to cause an overall cooling in most world regions. However, the Indian region is marked by an abundance of absorbing aerosols, such as black carbon (BC) and dust. The goal of this work was to understand the association between aerosols, particularly those that are absorbing in nature, and hightemperature extremes in north-central India during the pre-monsoon season. We use 30-year simulations from a chemistry-coupled atmosphere-only general circulation model (GCM), ECHAM6-HAM2, forced with evolving aerosol emissions in an interactive aerosol module, along with observed evolving SSTs. A composite of high-temperature extremes in the model simulations, compared to climatology, shows large-scale conditions conducive to heat waves. Importantly, it reveals concurrent positive anomalies of BC and dust aerosol optical depths. Changes in near-surface properties include a reduction in single scattering albedo (implying greater absorption) and enhancement in shortwave heating rate, compared to climatological conditions. Alterations in surface energy balance include reduced latent heat flux, but increased sensible heat flux, consistent with enhanced temperatures. Thus, chemistry-coupled GCM simulations capture an association of absorbing aerosols with hightemperature extremes in north India, arising from radiative heating in the surface layer. K E Y W O R D S absorbing aerosols, chemistry-coupled AGCM, ECHAM6-HAM2, extreme temperature, Indian heat wave, radiative forcing 1 | INTRODUCTION Extreme temperature and heat wave events in India during the pre-monsoon season (March-June) are critical in terms of their impact on human health, environment, agriculture and economy. Recent trends in extreme temperature are reported to be positive over India