Tumor Profiling and Targeted Treatment

How is tumor profiling advancing cancer care?

Cancer treatment has come a long way in recent years. The ability to sequence tumors from cancer patients has revealed specific gene mutations acquired by tumor cells, which underlie tumor growth, so called ‘driver’ mutations. 

This in turn has led to the development of targeted therapies based on specific driver mutations found in a given tumor type. Dozens of FDA approved targeted therapies are currently available, along with companion diagnostic tests to determine if the patient’s tumor harbors the specific gene mutation. In some cases, these targeted therapies are used as first line treatment for eligible patients.

Tumor profiling is also expanding treatment options for patients who fail first line therapy or who have rare or aggressive cancers. In some cases, a patient has a tumor that harbors a driver mutation for which a targeted therapy is approved for a different cancer type. 

These therapies have sometimes proven to be effective when used off-label for these patients. In other cases, tumor profiling has revealed driver mutations for which targeted therapies are in clinical development. 

These patients may be eligible for clinical trials.  Considering on-label and off-label use of FDA-approved therapies, as well as clinical trials, treatment options are available for most patients across the major cancer types.

Who is offering tumor profiling services?

There are dozens of commercial and academic laboratories offering tumor profiling for the purpose of targeting treatment to the underlying molecular drivers of cancer. Major commercial providers include Caris, Foundation Medicine, Molecular Health, and Paradigm. The best place to search for a laboratory offering tumor profiling is NextGxDx or the Genetic Testing Registry. Each laboratory’s tumor profiling assays may differ from others based on the number of genes tested, the laboratory’s ability to match genetic variants to treatment options, as well as important technical aspects. 

How can I get help interpreting the results of a tumor profiling test?

Many of the commercial vendors of tumor profiling services provide results in an easy to understand format. However, often it is helpful to review the results and discuss treatment options in the context of molecular tumor boards.

To learn more about molecular tumor boards, visit the American Society of Clinical Oncology

Is tumor profiling covered by insurance?

Coverage of next-generation sequence-based tumor profiling varies from one insurance provider to the next. The Center for Medical Technology Policy released a guideline in Aug 2015 to address coverage and reimbursement for tumor profiling. 

Clinical Trial for Genetically-Guided Tumor Treatment

NCI-MATCH is a clinical trial that analyzes patients’ tumors to determine whether they contain gene abnormalities for which a targeted drug exists (also known as “actionable mutations”) and assigns treatment based on the abnormality. NCI-MATCH seeks to determine whether treating cancers according to their molecular abnormalities will show evidence of effectiveness.

Each treatment in NCI-MATCH will be used in a unique arm, or substudy, of the trial. The trial opened for enrollment in August 2015 and there are currently 30 treatment arms open and enrolling patients. For most arms, the goal is to enroll 35 patients per treatment arm. However, a few arms address more common gene abnormalities and for those the goal is to enroll 70 patients per treatment arm.

Adults 18 years of age and older with advanced solid tumors, lymphomas and myelomas that are no longer responding (or never responded) to standard therapy and have begun to grow may be candidates to take part in the NCI-MATCH trial.

The trial will examine tumor biopsy specimens from about 6,000 patients. The specimens undergo DNA sequencing to identify those that have gene abnormalities that may respond to the targeted drugs selected for the trial. The drugs included in the trial have either been approved by the U.S. Food and Drug Administration (FDA) for another cancer indication or are still being tested in other clinical trials but have shown some effectiveness against tumors with a particular gene alteration(s). Treatment arms can be, and have been, added to the trial over time as drug companies and others develop promising targeted therapies.

Where can I learn more?

For more information about tumor profiling, read Clinical Tumor Sequencing: Opportunities and Challenges for Precision Cancer Medicine from ASCO University.  Read Duke's Kimberly Blackwell debate on the utility of genomic profiling in daily practice here.