KRAS is one of the most common oncogenic driver mutations in NSCLC, with prior attempts at direct inhibition being unsuccessful. In recent years, there has been significant advancement in the understanding of the biology of KRAS and its downstream effectors. This has translated into a multitude of important preclinical studies and clinical trials that are currently underway to find effective therapeutic drugs for KRAS mutant lung cancer. Ultimately, better therapeutics need to be engineered to arrive at RAS-driven precision medicine.

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Linifanib is active in advanced non-small cell lung cancer as second- or third-line therapy. Increased adverse event rates were observed at the high dose of linifanib.

8070 Background: Epidermal growth factor receptor inhibitors (EGFRIs) have shown benefit in solid tumors including non-small cell lung cancers. Despite these benefits, dermatologic toxicities are reported to affect 75–87% of those treated. These toxicities impact quality of life, and may also have implications for dose modification and tumor response. This study investigates the prevalence of infections complicating dermatologic toxicities to EGFRIs in lung cancer patients. Methods: Retrospective chart review methods were employed to analyze 90 lung cancer patients treated in the Skin and Eye Reactions to Inhibitors of EGFR and Kinases (SERIES) clinic. Cultures, biopsies, and viral stains were analyzed for pathogens and sensitivities. Selection criteria included patients treated with cetuximab or erlotinib at the time of referral. Selection was limited to initial patients and their follow-up visits in the time frame of August 2007 to June 2008. The study was approved by the institutional review board. Results: Thirty (33.3%) of 90 lung cancer patients had evidence of infection at sites of dermatologic toxicity. Twenty three (25.5%) patients were positive for bacterial infection. Six of these 23 patients had concomitant fungal or viral infection. Twenty (22.2%) patients cultured positive for Staphylococcus aureus. Of the patients with Staphylococcus aureus infections, 2 (2.2%) had tetracycline-resistant Staphylococcus aureus, 2 (2.2%) had Methicillin-resistant Staphylocccus aureus (MRSA), and 1 (1.1%) had tetracycline-resistant MRSA. Fifteen of the 23 bacterial infections were localized to the seborrheic region. Three (3.3%) patients had viral infections alone and 4 (4.4%) had fungal infections alone. All of the infected patients were followed to clinical resolution. Conclusions: The data suggests that lung cancer patients treated with EGFRIs have a high prevalence of cutaneous infections. Most notably, bacterial infections developed at anatomical sites previously affected by dermatologic toxicities. Proper recognition and management of these infections by clinicians is critical for maintaining antineoplastic dose therapy, dose intensity, quality of life, and dermatologic health in lung cancer patients treated with EGFRIs. [Table: see text]

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