Challenges in biomarker-based clinical trials for patients with gastrointestinal malignancies

ABSTRACT

Introduction

The goal of precision oncology is to match each patient with the most appropriate therapeutic agent based on patient- and tumor-specific characteristics. Many therapeutics in development target tumors with specific biomarkers, in addition to considering tumor histologic classification and clinical presentation.

Areas Covered

Appropriate patient selection for research studies is critical to elucidate the potential effectiveness of therapies in development, as well as to spare the toxicities from ineffective therapies in patients who are unlikely to benefit. Biomarker-based clinical studies provide a platform to bring forward the expanse of therapeutics beyond the use of chemotherapy, including novel immunotherapeutic and targeted strategies. There are a number of issues to be considered when developing these types of studies. They range from biomarker validity to patient enrollment and trial availability. In this review, we discuss challenges that are frequently confronted in the design, enrollment, and analysis of biomarker-based clinical trials for patients with gastrointestinal (GI) cancers.

Expert opinion

The challenges encountered in biomarker-based trials for patients with GI cancers must be considered and addressed early during drug development to ensure proper therapy and patient selection in a timeframe acceptable for both patient diseases and rapidly changing oncology standards.

KEYWORDS:

• Precision oncology
• biomarker
• NGS testing
• ctDNA
• gastrointestinal cancer
• tumor heterogeneity
• basket trial
• trial access

Article highlights

• Integrating biomarkers in clinical trial design requires expertise from many providers across multidisciplinary translational science.

• Basket, umbrella, and platform studies have been widely adopted for the simultaneous evaluation of therapies across different disease and molecular subtypes.

• Adaptive clinical trial platforms facilitate opportunities to incorporate emerging data, while both decreasing costs and increasing efficiency for biomarker trials.

• The availability of comprehensive molecular profiling provides opportunities to screen subjects for clinical trials based on biomarker selection.

• To support these efforts, institutional infrastructure should include expertise for both molecular and clinical interpretation for understanding the significance of unique molecular biomarkers.

Declaration of interest

N. Uboha has consulted for Taiho, Incyte, Ipsen, AstraZeneca, Astella, QED, and Pfizer and received research funding from Ipsen, EMD Serono, and Taiho.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers of this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by the University of Wisconsin Carbone Cancer Center, UW Carbone Cancer Center Support Grant P30 CA104520n.