Activating mutations in KRAS are highly prevalent in solid tumours and are frequently found in 35% of lung, 45% of colorectal, and up to 90% of pancreatic cancers. Mutated KRAS is a prognostic factor for disease-free survival (DFS) and overall survival (OS) in NSCLC and is associated with a more aggressive clinical phenotype, highlighting the need for KRAS-targeted therapy. Once considered undruggable due to its smooth shallow surface, a breakthrough showed that the activated G12C-mutated KRAS isozyme can be directly inhibited via a newly identified switch II pocket. This discovery led to the development of a new class of selective small-molecule inhibitors against the KRAS G12C isoform. Sotorasib and adagrasib are approved in locally advanced or metastatic NSCLC patients who have received at least one prior systemic therapy. Currently, there are at least twelve KRAS G12C inhibitors being tested in clinical trials, either as a single agent or in combination. In this study, KRAS mutation prevalence, subtypes, rates of occurrence in treatment-resistant invasive mucinous adenocarcinomas (IMAs), and novel drug delivery options are reviewed. Additionally, the current status of KRAS inhibitors, multiple resistance mechanisms that limit efficacy, and their use in combination treatment strategies and novel multitargeted approaches in NSCLC are discussed.

Background: There is limited published data regarding malnutrition risk in early stage lung cancer patients. This study aimed to: • assess the nutritional status of early stage lung cancer patients pre-operatively • assess the nutritional intake of a subset of patients post-operatively. Methods: Nutritional assessment was carried out in the pre-admission clinic on 51 patients undergoing lobectomy or pneumonectomy for lung cancer including BMI (body mass index), MST (malnutrition screening tool) and MUST (malnutrition universal screening tool). Dietary intake data was collected on a subset of 9 patients at 3 time points after surgery; day 1 or 2, day 3 or 4 & day 5 or 6. A customised photographic food atlas was developed based on the menu in St. James’s Hospital. A portion size record form was devised to assess the quantity of each food consumed by patients at each meal. A snack assessment form was also developed that covered any extra food consumed outside the hospital main meals. The daily energy (kcal) & protein (g) intake at the 3 time points were estimated for each patient. Results: MST identified more patients at malnutrition risk than MUST, 18% and 12% respectively. Of the study population, 10% of patients had a BMI <20kg/m², 57% were overweight or obese. At postoperative day 5/6, patients were on average meeting 56% of energy and 51% of protein requirements. 89% of the patient subset did not meet estimated energy (kcal) and protein (g) requirements by Day 5/6. Conclusion: Many lung cancer patients were malnourished or at risk of malnutrition pre-operatively according to MST & MUST screening tools. The patients were predominately overweight or obese and thus may not routinely be identified as requiring nutritional screening or nutrition intervention. Dietary intake post-operatively was inadequate, with the majority of patients not meeting their energy (kcal) and protein (g) requirements. As a result of this study, all lobectomy & pneumonectomy patients attending the pre-admission clinic have an MST completed as part of their assessment. To address the energy and protein deficits observed in the first post-operative week, we currently offer high protein high energy supplements as standard practice twice/day.