Immunotherapy should NOT be used as first-line treatment in ROS1+ cancer. However, researchers are investigating whether a combination of immunotherapy and chemotherapy might be useful in treating ROS1+ patients. The following explains what you need to know about immunotherapy and ROS1+ cancer.
What is immunotherapy?
Immunotherapy is treatment that uses a person's own immune system to fight cancer. One type of immunotherapy called immune checkpoint inhibitors (ICIs) are standard therapies for many types of advanced non-small cell lung cancer (NSCLC). ICIs stimulate the immune system so that it works harder to find and attack cancer cells. Other types of immunotherapy are also being investigated in clinical trials for ROS1+ cancer, such as CAR-T cell therapy (which modifies T cells from the patient’s own immune system to attack the patient’s tumor).
Despite the common use of ICIs in advanced NSCLC, targeted therapy (also called a TKI, or tyrosine kinase inhibitor) is the preferred first-line treatment for metastatic ROS1+ NSCLC. This is because:
Targeted therapies yield higher response rates than immunotherapy in the first-line treatment of ROS1+ cancer.
Targeted therapy is better tolerated than immunotherapy.
ROS1+ patients are unlikely to respond to immunotherapy.
Anecdotally, common side effects of immunotherapy (such as pneumonitis) might make patients ineligible to receive a TKI as a second-line treatment. Also, taking a TKI shortly after receiving immunotherapy can make TKI side effects significantly worse.
Targeted therapy and immunotherapy
Clinical trials have studied combining targeted therapy and immunotherapy in patients who have biomarker-driven NSCLC. Current medical consensus is that such combinations are not a good treatment option. For example, a phase 1/2 clinical trial for the combination of crizotinib plus nivolumab in ALK+ NSCLC patients found:
“Of the first 13 patients treated with nivolumab plus crizotinib, 5 (38%) developed severe hepatic toxicities leading to the discontinuation of the combination. Of these, two patients died and the presence of severe hepatic toxicities may have contributed to death.”
The study was closed and the combination treatment was discontinued due to the toxicities. Five of the patients had a partial response in this study.
Chemotherapy and immunotherapy
People who had ROS1+ NSCLC have not been evaluated in clinical trials that tested chemotherapy and immunotherapy combinations, so as yet there is no data indicating whether such combinations are effective for ROS1+ cancer. However, people who had ALK+ NSCLC were evaluated in some of these clinical trials (ALK+ NSCLC has aspects in common with ROS1+ NSCLC). A 2023 review article of immunotherapy for ALK+ NSCLC concluded, "The available clinical trial and retrospective data suggest that the clinically available immunotherapies for lung cancer have limited to no role in the treatment of patients with ALK+ NSCLC." Current thinking of expert ROS1 clinicians is that chemotherapy-immunotherapy combinations do not currently have a role in treating ROS1+ NSCLC.
To learn more about the latest research in immunotherapy, visit our Drugs to Treat ROS1+ Cancer page.