ROS1 and Lung Cancer

Support for this educational program provided by Amgen, AstraZeneca, Blueprint Medicines, Bristol Myers Squibb, Genentech, Lilly Oncology, Merck, Novartis and Pfizer.

When tumor tissue is looked at under a microscope, physicians can see what type of cancer it is. Physicians can also look for changes in the DNA of the tumor that might be causing the tumor to grow. Sometimes these changes are called biomarkers or molecular markers.

One way to think about it is that our DNA is like an instruction manual. If there is a typo in the instruction manual, the cell receives wrong instructions and can grow into cancer. Biomarker testing looks for those typos, so physicians know if you are a candidate to receive a targeted therapy that directly addresses those typos. 

An error in the ROS1 gene is one biomarker that physicians look for in non-small cell lung cancer. If you have non-small cell lung cancer, it is important to talk to your doctor about comprehensive biomarker testing to see if you have an error in the ROS1 gene or another biomarker. The results of this testing influence your treatment options. To learn more about biomarker testing, visit Lung.org/biomarker-testing.  

What is a ROS1-positive cancer?

In ROS1-positive lung cancer patients, the ROS1 gene fuses (joins) with part of another gene. This activates the ROS1 gene in a way that causes uncontrolled cell growth and cancer. This gene change is called a ROS1 fusion or ROS1 rearrangement. The ROS1 gene can fuse with many different partners. The most common in lung cancer is the CD74 gene. When ROS1 fuses or joins with another gene and causes lung cancer, a patient is said to be ROS1-positive. At this point, the recommended course of treatment is the same for patients who are ROS1-positive, regardless of the very specific type of ROS1 rearrangement you may have. 

How do you know if you have ROS1-positive lung cancer?

To determine if your lung cancer is ROS1-positive, you need to test the tumor tissue or your blood. There are several different types of tests that doctors use.

• FISH analysis: looks at changes in the chromosomes through tissue under a microscope
• Immunohistochemistry: looks for proteins in the cell under a microscope
• Next generation sequencing (or comprehensive biomarker testing): tissue from a patient’s tumor (gathered from a biopsy) is placed in a machine that looks for a large number of possible biomarkers at one time
• Liquid biopsy: looks for tumor DNA in the blood

Your doctor may perform several of these tests at the same time to help confirm results.

Learn more about the different types of biomarker tests here.

Who is likely to have ROS1-positive lung cancer?

The ROS1 gene is altered in about 1-2% of lung cancer patients and generally appears in adenocarcinoma non-small cell lung cancer. Patients who are ROS1-positive tend to be younger than the average lung cancer patient and have little to no smoking history. 

What are the treatment options for someone with ROS1-positive cancer?

Knowing if you have ROS1-positive lung cancer is important no matter your stage of lung cancer but has the most treatment implications for stage four patients.

First-line Treatment

Patients with stage four ROS1-positive lung cancer will likely be prescribed a pill called a ROS1 tyrosine kinase inhibitor (TKI) or ROS1 inhibitor. There are currently two FDA-approved options: crizotinib or entrectinib.

Second-line Treatment

Within a few months to years, the cancer is likely to evolve, and the ROS1-inhibitor may stop working. Some patients will develop a new resistance mutation. Your doctor may want to do a tissue or liquid biopsy to check for this. Once a patient develops resistance to a ROS1-inhibitor, your doctor may recommend a clinical trial or use of another targeted therapy that is considered off-label. This means it is approved to treat a different biomarker (like ALK) but not approved to treat ROS1. If a patient has been on crizotinib and the cancer spread only to the brain, then your doctor might try entrectinib, which can reach tumors in the brain. Cancer that has spread to the brain may also be treated with other ROS1 inhibitors with good activity in the brain, or brain radiation such as stereotactic radiosurgery (SRS).

Third-line Treatment

If the cancer continues to grow after second-line treatment, the next option would include a clinical trial, chemotherapy with or without a ROS1 inhibitor, or chemotherapy with or without immunotherapy.

Work with your doctor to discuss your goals and options each time you have to make a treatment decision. The three big questions to ask are:

1. What is the goal of this treatment?
2. What are the potential side effects?
3. What other options do I have?

Research is happening at a rapid pace and your doctor should be up to date on the recommendations for your specific type of lung cancer. If you don’t feel comfortable with the answers you are receiving, do not hesitate to seek out a second opinion.