This module will review the medical oncologist’s armamentarium and ways of using it in daily practice. The focus will be at cytotoxic chemotherapy and targeted therapies. The various types of cytotoxic chemotherapy, their targets, their toxicity, the principles of dosing and the rationale behind combining such therapies will be elucidated. A real-life example from the presenter’s practice will illustrate the application of chemotherapy in conjunction with other treatment modalities.

The second part of this module will review the concept of targeted therapy of cancer and the various molecular targets and agents that have been exploited successfully thus far. 

Increased knowledge of the molecular pathogenesis of cancer has led to increased interest in molecularly targeted agents (MTAs), which target specific oncogenic drivers. MTAs differ from traditional cytotoxic agents in various aspects, including their toxicity profiles and the potential availability of predictive biomarkers of response. The landscape of phase I oncology trials has changed impressively to adapt to these novel therapies and to improve the efficiency of drug development.

New study designs and selection of patients based on genetic or molecular biomarkers, pharmacokinetic and pharmacodynamic analyses and the early evaluation of efficacy might yield expedited approval because efficacy is often already observed in these early phase trials. The application of molecular tumor profiling for matched therapy and the testing of drug combinations based on a strong biological rationale are also increasingly seen in phase I studies.

This module will demonstrate that (molecular) biomarkers are indispensible in the era of personalized cancer medicine. The need for biomarkers in clinical oncology care and oncology drug development will be elucidated and will be illustrated by examples from actual practice. The module will also address the “biomarker innovation gap” (too much biomarker discovery - too little development to application) and ways to bridge this gap.

This module will show how a specific biomarker can be developed into a companion diagnostic for a targeted cancer agent. Companion diagnostics have become a highly critical element in drug development, in particular in oncology. Whilst offering great opportunities, companion diagnostics also go along with various challenges and understanding the complexities is key to success. The presentation will provide an overview including the current regulatory framework for companion diagnostics, co-development of drug and companion diagnostics, market implementation aspects of such in vitro diagnostic tests, as well as an outlook on where this may lead us in the future.

One of the most important steps in the drug development process is the decision to move from early-stage (Phase I/II) trials to late-stage or ‘full’ development (Phase III). In early-stage trials, the focus is on getting clinical proof of mechanism (target engagement) and proof of concept (anti-tumor activity) and tolerability of the experimental drug. The number of patients, and thus the associated costs for the early phases, are relatively limited. Phase III studies are carried out in large numbers of patients, comparing the experimental drug with the best existing treatment or standard of care in a particular disease. Obtaining the necessary pivotal Phase III data on efficacy and safety to prepare for a regulatory dossier is very costly. This module illustrates opportunities, difficulties and pitfalls in the full clinical development of targeted anticancer agents based on historical examples.