Precision oncology: A new era of cancer clinical trials

Abstract

Traditionally, site of disease and anatomic staging have been used to define patient populations to be studied in individual cancer clinical trials. In the past decade, however, oncology has become increasingly understood on a cellular and molecular level, with many cancer subtypes being described as a function of biomarkers or tumor genetic mutations. With these changes in the science of oncology have come changes to the way we design and perform clinical trials. Increasingly common are trials tailored to detect enhanced efficacy in a patient subpopulation, e.g., patients with a known biomarker value or whose tumors harbor a specific genetic mutation. Here, we provide an overview of traditional and newer biomarker-based trial designs, and highlight lessons learned through implementation of several ongoing and recently completed trials.

Statistical controversies in clinical research: basket trials, umbrella trials, and other master protocols: a review and examples

“…Here, we discuss several in more detail. A detailed review of biomarker-based trial designs from a statistical design and analysis perspective was recently given by Renfro et al [33].…”

“…Specifically, when molecularly targeted treatments are studied in early phase trials, it must be decided whether to allow all eligible patients with a given disease to enroll, whether to restrict enrollment to those patients hypothesized to experience the greatest benefit from targeted therapy, or whether to do some combination of the two through mid-trial adaptive measures [32,33]. In the case of a standard 'all-comers' design, the targeted agent may only benefit a selected group of patients and thus a strong subgroup effect may instead appear as a weak overall effect, though randomization of markerpositive and marker-negative patients to targeted versus nontargeted treatment can play an important role of validating the treatment-by-marker interaction hypothesis.…”

Application of Multimodality Imaging Fusion Technology in Diagnosis and Treatment of Malignant Tumors under the Precision Medicine Plan

“…Precision oncology is an important branch of precision medicine, that uses “individual treatment”, has the advantage of causing less trauma, causing fewer complications, and offering good prognosis; therefore, precision oncology has become the cutting-edge field that needs prioritization in precision medicine. [7] Precision oncology must always consider three aspects of malignant tumors: prevention, diagnosis, and treatment, none of which is dispensable. [8] In the background of the current social medicine, any clinical method that can achieve individual diagnosis and treatment of malignant tumors, improve therapeutic effects, and reduce adverse effects belongs to the precision oncology.…”

Personalized medicine: biomarkers and companion diagnostics

“…In this perspective, particularly in oncology, it is now essential that future clinical studies are designed so as to match the therapy to a specific molecular makeup [18,19].…”