The good news
The U.S. Food and Drug Administration (FDA) approved zidesamtinib for adults with locally advanced or metastatic ROS1-positive (+) non-small cell lung cancer (NSCLC) who received a prior ROS1 inhibitor.
Why it’s important
The ROS1 gene is felt to be important in the regulation of various processes within the cell. A ROS1 fusion or rearrangement occurs when the ROS1 gene combines with part of another gene. The change in the gene can cause uncontrolled cell growth and cancer. The ROS1 gene is altered in about 1-2% of patients with lung cancer, usually NSCLC of the adenocarcinoma type. Patients who are ROS1+ tend to be younger than the average patient with lung cancer and have little to no smoking history.
Zidesamtinib is a next generation oral tyrosine kinase inhibitor (TKI) that targets the abnormal ROS1 gene and can help slow down or stop the growth of cancer cells. The drug distinguishes itself from some of the other ROS1 inhibitors by being more selective for ROS1 and active against resistance mutations such as G2032R. The drug also has less neurologic toxicity and is active against brain metastases.
The approval of zidesamtinib is based on the results from a global ARROS-1 phase I/II clinical trial in patients with advanced or metastatic ROS1+ NSCLC who were previously treated with a ROS1 inhibitor. Among the 117 patients in the study, 44% responded to treatment, including those with resistance mutations and brain metastases. The treatment provided lasting benefit, with 69% of the patients having control of their disease at 12 months.
Zidesamtinib was very well tolerated. The most common side effects associated with treatment included: swelling, peripheral neuropathy (nerve pain/tingling), constipation, fatigue and shortness of breath.
What it means for patients
ROS1 fusions/rearrangements represent an abnormality in the cancer cell that can be treated with “targeted” therapy. Because of its rarity, it is important that patients have biomarker testing done on their cancer to determine if a ROS1 abnormality is present, because zidesmatinib represents another treatment option for patients with ROS1+ NSCLC. Notably, the encouraging responses in patients who have already received many other treatments represents meaningful progress in the treatment of patients with this type of lung cancer.
What to look for
Zidesmatinib represents the results of efforts to develop new and improved targeted therapy for people with ROS1+ lung cancer. Look for trials utilizing this agent as an initial treatment. Future research will be focused on understanding why resistance to treatment occurs and how to better manage side effects. The goal of these research efforts is to eventually find a cure for ROS1+ lung cancer as well as other oncogene-driven cancers. Expect that development of new drugs will continue.