The good news
The U.S. Food and Drug Administration (FDA) approved taletrectinib for adults with locally advanced or metastatic ROS1-positive (+) non-small cell lung cancer (NSCLC).
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 or no smoking history.
Taletrectinib is an 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 was evaluated in 2 clinical trials, TRUST-I (NCT04395677) and TRUST-II (NCT04919811). In 157 patients, who had not been previously treated with a ROS1 inhibitor, 85-90% had a significant reduction in their cancer that often lasted over one year. For the 113 patients who received previous treatment with ROS1 inhibitor drugs, the response to treatment was 52-62% and lasted more than 6 months for most patients. Taletrectinb also demonstrated activity in brain metastases and the ROS1 resistance mutation G2032R. The most common side effects associated with treatment included: liver abnormalities, diarrhea, inflammation of the lung (pneumonitis), electrical irregularities in the heart, elevated uric acid, and muscle aches and bone fractures. Other side effects such as alteration of taste and dizziness were low grade.
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 molecular/genetic testing done on their cancer to determine if a ROS1 abnormality is present.
What to look for
Taletrectinib represents the results of efforts to develop new and improved targeted therapy for ROS1+ lung cancer patients. Unfortunately, this drug is not a cure for most patients. Future research will be focused on understanding the mechanisms of drug resistance and how to overcome them. 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.