Objectives	To be able to perform assessment, including ordering and interpreting predictive biomarkers of response and treatment and counselling of patients with cancer who will be receiving targeted therapy (small molecule signal transduction or kinase inhibitors, hormonal agents, antibodies or antibody drug conjugates) To describe the common toxicities seen with these agents when used as a single agent or in combination with other targeted agents or chemotherapy
Key Concepts	Recognise that the basic principles of oncogenesis provide the biologic rationale for the classification of different types of targeted therapy in cancer, eg, small molecules, antibodies, anti-hormonal agents, or antibody drug conjugates Define a targeted agent in the context of DNA damaging agent or a drug harnessing the immune system for its activation Explain the differences between molecularly agents and non-targeted agents, such as DNA damaging or tubulin binding agents Describe the basic principle of the use of a predictive biomarker which could be gene mutation, eg, BRAF, gene rearrangement eg, TRK, gene amplification such as human epidermal growth factor receptor 2 (HER2) or protein expression, such as oestrogen receptor Demonstrate an understanding of basic principles of pharmacokinetics such as role of loading dose for drugs with a long half-life, eg, bevacizumab Recognise the importance of pharmacodynamics in determining the dose and schedule of targeted agents eg, difference from determining only maximally tolerated dose in chemotherapeutic agents Evaluate the use of targeted agents alone or in combination with other classes of drugs eg, other targeted agents (eg, BRAF inhibitor + MEK inhibitor) or in combination with chemotherapy (eg, cetuximab + folinic acid, fluorouracil and irinotecan chemotherapy) Summarise different classes of common toxicities associated with targeted agents, like skin rash or diarrhoea, and specific targeted therapy–based toxicities such as cardiotoxicity with HER2 targeting agents Recognise the importance of clonal evolution and emergence of resistance mutations eg, detection of epidermal growth factor receptor (EGFR) T790M mutation in patients with EGFR mutated non–small-cell lung cancer treated with first generation EGFR inhibitors such as gefitinib or erlotinib
Skills	Demonstrate the ability to: Contribute actively to a variety of targeted therapy clinical scenarios Discuss targeted therapy treatment options Select the correct patient for targeted therapy, based on histology, staging, mutations, and performance status Interpret biomarker data eg, protein expression on immunohistochemistry, like oestrogen receptor positivity, HER2, or interpretation of mutations in tumour eg, EGFR mutations or germline mutations such as BRCA1 Optimally sequence targeted therapies based on an understanding of resistance mechanisms and biomarker-based response assessment Prescribe targeted agents as flat dose for small molecules, such as osimertinib or as mg/m2 as with cetuximab and mg/kg for bevacizumab Recognise and manage targeted therapy adverse events Perform a risk-benefit assessment for patients considering adjuvant targeted therapy