Observational StudyModel to Predict pCR and IrAEs in Early Stage Non-small Cell Lung Cancer

Lung cancer is the chief cause of cancer death. The new standard-of-care (SOC) in operable lung cancer combines chemotherapy and an immune-stimulating drug before the surgery (neoadjuvant approach). This results in a large increase in complete cancer clearance rates compared to chemotherapy alone (±30% with combination vs ±4% with chemotherapy alone), leading to much better long-term survival and probably many more cures. However, most still don't achieve complete clearance, and a few have increases in, or spread of, their tumors while on treatment. Therefore, we need to understand why some patients benefit (responders) and others don't benefit (non-responders) on an immunotherapy-based treatment. Also, some patients unpredictably develop severe immune-type side effects related to the immunotherapy drug, although such side effects may be associated with improved anti-cancer effects. In short, the same treatment can result in complete cancer clearance in one patient, and in a worst-case scenario may result in severe toxicity or fail to control spread/growth thus precluding surgery. The immune system obviously plays a key role in both benefit and harm, yet most of the research in this field has focused only on the cancer. We plan an in-depth study in 60 patients, focusing on the cancer as well as the patient's immune system, pre-surgery. This will enable us to identify factors predicting complete cancer clearance, and the occurrence of immune-type side effects. Using highly sophisticated resources available to us here in London, we will develop predictive models enabling better patient management (including possible avoidance of surgery), and identification of key biological differences between major responders and non-responders, to highlight important new targets for the development of even newer and better therapies.