In this special issue related to biomarkers and ethics in oncology trials, international experts have provided their perspectives on the most important elements related to their successful design, conduct and implementation of their results into clinical practice.  Dr. Silvia Novello and myself review how there has been a renewed optimism in achieving major improvements in the clinical care of patients based upon the identification and use of biomarkers that relate to the underlying biology of cancer.

Due to the recent developments in the field of molecular diagnosis, it has become evident that there is no such entity as cancer per se, as there are considerable biological differences even within a particular anatomical subtype. Genomic characteristics do not only help to better define tumor subtypes, but frequently they provide the opportunity to target these subtypes as well.

Ethics can best be thought of as the moral principles that underpin good behavior. However, how this is defined is open to wide interpretation, and depends on factors such as societal norms and religion. Thales of Miletus (624 BC – 546 BC) advised his contemporaries to avoid doing what they would blame others for doing, and similar expressions of this concept abound throughout a range of moral philosophies. In medicine, the concept of non-maleficence (i.e., not harming the patient) is established as a pillar of physician behavior.

Due to the innovations in the field of oncological treatment that have profoundly changed our perception of modern cancer therapy, the design of clinical trials had to be modified appropriately with the purpose of allowing for the assessment of the distinct effects of new drugs. This means that long-standing paradigms had to be abandoned, and new principles took their place.

Phase I trials consist of the dose escalation portion and the cohort expansion portion. The dose escalation part is dedicated to assessment of PK, safety and MTD. This segment usually encompasses only very few patients for each of several dose levels. In the expansion phase, a greater number of patients is recruited into one or two selected dose levels with the purpose of decreasing confidence intervals.

Phase II studies provide initial assessment of efficacy in a more homogeneous patient population. Screening out of ineffective drugs is an objective here, as is the identification of promising new agents for future evaluation. The activity of a compound is assessed in a given tumor type, which allows for selection of tumor types for further study. Also, safety (types and incidence of AEs) is further defined in a specific patient population/ disease setting.

Commonly used endpoints are based on survival, tumor response, and symptom assessment. Historically, overall survival (OS) has been viewed as the most effective measure as it addresses the biology of the tumor and the natural history of disease. PFS possesses significance because it assesses tumor shrinkage and stabilization of disease.

Quality of life (QoL) assessment adds useful information to the efficacy and safety data obtained in clinical studies. It contributes to the evaluation of different treatments and identifies patients who might benefit from supportive interventions. QoL data can be used to inform policy and resource allocation, reveal benefits to patients despite objective toxicity, and be of prognostic value. Evaluation of patient’s QoL might help to determine the suitable moment to start specific palliative interventions.