Implications and opportunities of precision medicine in rare malignancies

ABSTRACT

Introduction: In aggregate, about 20% of all cancers can be considered rare. In addition, molecularly defined subsets of more common cancers are generally rare. Many rare cancers urgently need development of efficacious therapeutics, yet their rarity makes it difficult to conduct standard clinical trials. The advent of molecular profiling of cancers, however, may offer an opportunity for more thoughtful and successful development of new effective treatments.

Areas covered: This manuscript describes instances in which drugs have been approved for rare cancers, and describes the potential value and challenges of new policies and research that may lead to more broad development of drugs based on the molecular characterization of a patient’s tumor.

Expert opinion: Although challenges in use of any methods for development of therapeutics for rare cancers exist, international collaboration, broad molecular profiling for research, and new trial designs such as basket designs and tumor agnostic designs, have promise to develop the evidence needed to assure that drugs will or will not be effective in rare cancers. Complimentary studies, such as those of exceptional responders, will add to the body of understanding that will hopefully lead to the discovery and development of effective treatments for many rare cancers.

KEYWORDS:

• Next generation sequencing
• genomic abnormalities
• precision medicine
• rare cancers

Article highlights

• Several genetic abnormalities exist in different histological cancers, and may be addressable with approved or investigational treatments.

• Several common cancers also have rare subsets of tumors characterized by molecular abnormalities that are crucial for that cancer’s behavior.

• The orphan drug act presents an opportunity to present data for drug approval for rare cancers.

• Imatinib and trastuzumab are examples where FDA approval has been obtained for treatment of rare malignancies.

• Additional study designs that can be useful or are directly targeted to rare cancers have been developed to assist therapeutics development.

This box summarizes key points contained in the article.

Declaration of interest

The manuscript was prepared as part of official duty as employees of the National Cancer Institute and had no other funding. The opinions expressed in this article are those of the authors, and not necessarily those of the Cancer Diagnosis Program, the National Cancer Institute or the National Institutes of Health. 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.

Additional information

Funding

This paper was not funded.