ROS1 Testing Is Increasingly Important in Lung Cancer

Although ROS1 mutations are quite rare in patients with non-small cell lung cancer (NSCLC), testing for the mutation in all who have the disease is important, as it can play a vital role in determining a treatment plan.

“ROS1 we've known about for a long time: It's about 2 percent of lung cancer. It works very well when you give crizotinib (Xalkori),” said D. Ross Camidge, M.D., Ph.D. But some ROS1-positive NSCLCs in the body or brain are — or become — resistant to that drug, noted Camidge, director of thoracic oncology at the University of Colorado School of Medicine, in an interview with CURE at the 2017 World Conference on Lung Cancer (WCLC).

In March of 2016, Xalkori became the first and only agent that the Food and Drug Administration (FDA) has approved to treat metastatic NSCLC that tests positive for the ROS1 mutation. However, while the agent is usually effective in treating the disease, one of its downfalls is that it does not penetrate the central nervous system (CNS), meaning that it cannot cross the blood/brain barrier to treat the spread of cancer to the brain.

Luckily, a promising agent that does penetrate the CNS is moving through the pipeline.

“That shows a dramatic improvement, recognizing the Achilles heel of the CNS for crizotinib,” Camidge said.

As more agents move into this space, it is going to be even more important that patients with NSCLC are tested for the ROS1 mutation. The American Society of Clinical Oncology (ASCO) recognizes this, and, in August of 2017, updated its guidelines for patients whose NSCLCs are characterized by EGFR, ALK and ROS1 mutations. The guidelines state that patients with the ROS1 gene mutation who have not been pretreated with an ALK inhibitor should be given Xalkori. If such a patient is already taking an ALK inhibitor, ASCO recommends standard chemotherapy. The guidelines do not mention investigational drugs, but will likely be updated as new agents are approved.

Of course, these recommendations all come with the caveat that the patient undergo molecular testing before the start of treatment.

Matthew Gubens, M.D., echoed the importance of genetic testing, which is becoming less invasive and more widespread as the field moves from away from tissue sampling and toward liquid (blood-based) biopsies.

“Some of those targets are in patients whom we really haven’t historically thought of for targeted therapy,” he said. “It is just going to become even more important to offer this kind of testing across the board to all nonsquamous and, eventually and hopefully, squamous patients.”

Disclosure: This article is sponsored content.