ROS1 and Lung Cancer

The videos above were produced in 2021. For the latest treatment options, speak with your doctor.

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

What is a ROS1-positive cancer?

Errors in the ROS-1 gene are one type of lung cancer biomarker. A patient is said to be ROS1-positive when the ROS1 gene fuses, or joins, with part of another gene. This gene change is called a ROS1 fusion, or ROS1 rearrangement, because it changes the ROS1 gene in a way that causes uncontrolled cell growth and cancer. The ROS1 gene can fuse with many different partner genes, but the most common fusion in lung cancer is the CD74 gene. The targeted therapy for ROS1-positive lung cancer is the same regardless of the specific type of ROS1 rearrangement a patient has.

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

To find out if your lung cancer is ROS1-positive, tumor tissue testing, or blood testing will need to be done. There are several different types of tests that doctors use, including FISH (fluorescence in situ hybridization) analysis, which looks at changes in the chromosomes through tissue under a microscope. Next-generation sequencing (NGS), also called comprehensive biomarker testing, is another testing method. NGS testing is completed by placing tumor tissue into a machine that looks for many possible biomarkers at one time. In some situations, a patient may not be able to have the biopsy needed to perform NGS testing, so a liquid biopsy is recommended instead. A liquid biopsy can look for certain biomarkers in a patient’s blood. Talk to your doctor to make sure one of these tests was performed.

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.

Who is likely to have ROS1-positive lung cancer?

ROS1 gene changes occur in about 1-2% of patients with lung cancer and generally appears in adenocarcinoma non-small cell lung cancer (NSCLC). Patients who are ROS1-positive tend to be younger than the average patient with lung cancer 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. However, it has the most treatment implications for patients with advanced-stage lung cancer. Treatment implications tell you what your test results means for your treatment, which therapies are likely to work best for you, and what your care team may recommend next. 

Research on ROS1-positive lung cancer, and treatment plans may vary from patient to patient. The treatment a patient receives and the order in which it is given, depends on the type of ROS1 fusion, how well the patient tolerates the medication and if the cancer has spread to the brain. Below is a high-level overview of treatment options for ROS1-positive lung cancer, but your personal treatment plan may be different.

First-line Treatment

Patients with advanced-stage ROS1-positive lung cancer will likely be prescribed a pill called a ROS1 tyrosine kinase inhibitor (TKI) or ROS1 inhibitor. The current FDA-approved options are crizotinib (Xalkori), entrectinib (Rozlytrek) and repotrectinib (Augtyro), and taletrectinib (Ibtrozi, Nuvation Bio Inc.).

Second-line Treatment

Over time, the cancer may change and the ROS1inhibitor may stop working. This can happen if the cancer develops a resistance mutation, a gene change that causes the cancer to stop responding to a certain drug. Your doctor may want to do a tissue or liquid biopsy to check for this change. If a patient develops resistance to a ROS1 inhibitor, your doctor may recommend a clinical trial, switching to another ROS1-inhibitor, or another targeted therapy that is considered off-label. This means the therapy is approved to treat a different biomarker like ALK, but is not approved to treat ROS1.

Third-line Treatment

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

Brain Metastasis

ROS1-positive lung cancer can sometimes spread to the brain, called metastasis. Cancer that has spread to the brain may be treated with ROS1 inhibitors that can reach the brain and stereotactic radiosurgery (SRS), a type of brain radiation.

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.