What is the treatment for ROS1-positive lung cancer?

ROS1-positive lung cancer refers to non-small cell lung cancers (NSCLCs) that test positive for a mutation in the ROS1 gene. This gene contains instructions for a protein called ROS1, which is involved in several important cell functions, including cell growth.

Mutations to the ROS1 gene can create abnormal, cancerous versions of these proteins. The type of gene mutation that occurs in ROS1-positive NSCLC is called “gene fusion” or “gene rearrangement.” This type of mutation occurs when a ROS1 gene merges with another gene.

After a ROS1 fusion, cells start making abnormal versions of the ROS1 protein. Normally, cells grow and expire following a tightly controlled, step-by-step process guided by the activation—and inactivation—of genes and proteins. Abnormal ROS1 proteins do not follow this process. They exist in a perpetually active state that leads to the uncontrolled growth of cells.

In a person with ROS1-positive NSCLC, this is occurring in the lungs. These mutations are found in less than 2 percent of cases of NSCLC. Unlike many other mutations that can result in lung cancer, ROS1 fusions are not associated with smoking (the leading cause of lung cancers), and occur in nonsmokers as well as smokers.

How is ROS1-positive NSCLC treated?

The first step in treatment is diagnosis. In order to determine if a cancer is ROS1-positive, a healthcare team will collect a tissue sample from the tumor or tumors in the lung (or potentially both lungs, if cancer is affecting both lungs). The sample or samples will then be sent to a lab for testing, which will examine how the cancer looks and behaves at the cellular level.

This process is called a biopsy, and is a standard test used during a lung cancer diagnosis. There are also liquid biopsies, which test biomarkers in blood, which may be used in some cases.

One of the goals of biopsy is to identify biomarkers, proteins or gene mutations (like ROS1 fusion) that help healthcare providers understand how the cancer is growing, and potentially, what treatments it might respond to.

What is the initial treatment for ROS1-positive NSCLC?

Targeted therapies are cancer drugs that work by blocking a specific protein or process that the cancer is using to grow. This can help shrink the tumor or slow down its growth. There are several targeted therapies available for ROS1-positive NSCLC, called ROS1 tyrosine kinase inhibitors (TKIs) or ROS1 inhibitors.

Treatment for ROS1-positive NSCLC often includes these therapies. The choice of drug will depend on many factors, including the stage of the cancer and whether the cancer has spread to other parts of the body. For example, surgery to remove a tumor is the preferred treatment whenever possible, and certain targeted therapies for ROS1-positive cancers have the ability to cross the blood-brain barrier and reach metastatic tumors in the brain.

It’s important to remember that treatment for NSCLC is highly individualized and often involves a combination of therapies. A cancer being ROS1-positive is an important factor when making treatment decisions, but it is not the only factor. The stage of the cancer, the grade of the cancer, a person’s overall health, their age, and their preferences are all factors that will need to be considered.

What if the cancer stops responding to targeted therapy?

Sometimes ROS1-positive NSCLC will not respond to a specific targeted therapy, or it will stop responding to a targeted therapy over time. This is called drug resistance.

If this occurs, a healthcare team may make several recommendations for continuing treatment:

• Switching to a different ROS1 inhibitor
• Repeating biopsy and biomarker testing
• Switching to a different type of targeted therapy that targets a different type of biomarker
• Chemotherapy, which may be used alongside a targeted therapy
• Chemotherapy with an immunotherapy (a cancer therapy that helps the body’s immune system identify and attack cancer cells)
• Radiation therapy to target specific tumors, typically used in combination with drug therapies
• Clinical trials

Always talk to your healthcare team about the potential benefits and side effects of any cancer treatment that is being recommended. For information about diagnosis and treatment for yourself or a loved one, a healthcare team will be your best source of information.