Impact of the biomarker enrichment strategy in drug development

ABSTRACT

Introduction

Recently, new oncology therapies were developed using a biomarker for patient selection. In the era of cancer genomics, this paradigm is expected to increase. Most cytotoxic chemotherapies and other oncological treatments were historically approved without a biomarker. However, this strategy seems to be less efficient. We reviewed the biomarker-based strategy and its impact in cancer drug development.

Areas covered

Oncology drugs approval rates are low and most of the drugs that failed to be approved were in late stages of development. In addition to that, attrition rates are high. The use of biomarkers in drug development has shown higher response rates, longer progression-free survival rates and even higher overall survival rates. Hence, the biomarker-based strategy seems to be associated with more successful drug programs, including a shorter timeline and higher likelihood of success.

Expert opinion

Even though the development of biomarker-driven strategies is promising, there are some challenges surrounding this field of study, such as reducing the cost of drug development, enhancing the technique of biomarkers identification (aiming more specific biomarkers and considering tumor heterogeneity) and exploring the role of next-generation sequencing tests in drug development. Also, collaboration between clinicians, scientists and regulatory agencies is fundamental.

KEYWORDS:

• Biomarker
• Clinical trials
• Drug development
• Personalized therapy
• Precision oncology

Article Highlights

• New oncology therapies have been recently evolved to the use of biomarkers for patient selection.

• The traditional approach for drugs approval is marked by a high attrition rate and a longer clinical phase of development for these drugs.

• The oncology drugs have more access to FDA special programs than non-oncology drugs. Consequently, median approval phase is generally shorter for oncology drugs. However, oncology drugs clinical phase is usually longer than non-oncology drugs.

• Biomarkers could be one strategy to refinement of early-phase trials, which may select drugs that have a greater possibility to succeed in phase 3 trials.

• The incorporation of a biomarker-driven rationale for drug development was not only associated with improvements in response rate, progression-free and overall survival for FDA-approved anticancer agents, but also with faster total time of clinical drug development.

• The development of biomarkers comes with challenges, such as inter and intratumoral heterogeneity, the need for technical analytical validation of tests and the search for samples more feasible to be tested.

• Due to the findings of several new and actionable biomarkers, it is important to consider multiplatform for validation of predictive biomarkers, including comprehensive genomic profile using next-generation tests.

• Currently, the trend in oncology clinical trials considering biomarkers includes short phase 1 trials with expansion cohorts, as well as employment of umbrella and basket trials.

• The agnostic approvals have led to a new paradigm in biomarker-driven drug development.

• There is a wide field of study regarding biomarkers and drug development, with several questions to be discussed. Some of them includes the role of ctDNA in this context, how to overcome tumor heterogeneity, how to reduce costs of drug development and how to optimize the clinical trials.

Declaration of interest

Dr. Jardim receives speaker fees from Roche, Janssen, Astellas, MSD, Bristol-Myers Squibb and Libbs, as well as consultant fees from Janssen, Bristol-Myers Squibb and Libbs. The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewers Disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.