RET rearrangements and treatment possibilities in NSCLC

Non-small cell lung cancer (NSCLC) makes up about 85% to 90% of all lung cancers. NSCLC has now several treatment options, but in general, lung cancer continues to be the leading cause of death in men and women diagnosed with cancer. Among the available treatment options, there are chemotherapies such as paclitaxel, carboplatin, pemetrexed, gemcitabine, etc. There are also more novel therapies, such as monoclonal antibodies, which we have mentioned in previous posts, such as Nivolumab, Pembrolizumab, Ipilimumab, Bevacizumab, etc. Other types of therapies are more specific depending on gene expressions in the tumor. There are some genetic tests that are recommended for patients with a diagnosis of NSCLC, in order to know more specific information about the disease, and to help them have a more efficient treatment. Some of the tests include verifying if there are EGFR mutations and ALK and ROS1 rearrangements. If there are EGFR mutations detected, some available treatments for the patients are Erlotinib, Afatinib, Gefitinib, Osimertinib, and Dacomitinib. If ALK rearrangements are found, there are treatments such as Crizotinib, Alectinib, and Ceritinib. Crizotinib can also be used in patients whose tumors have ROS1 rearrangements.

There is another genetic rearrangement that is less popular, but is a target for treatment in case it is present in NSCLC tumors. The RET rearrangement is present in around 1% to 2% of the patients with metastatic NSCLC. The RET rearrangement is usually detected using RT-PCR. Multikinase inhibitors have been used to target RET (which is a kinase), but some studies have shown that even though RET is included in the target group, only 15% to 30% of the patients responded to the treatment. This means that a more specific treatment is needed. There has been some research to target RET inhibitors, which include two agents: LOXO-292 from Loxo Oncology, Inc. and BLU-667 from Blueprint Medicines. In a phase 1 clinical trial using the first agent, there was a response rate of 68% among the 38 patients enrolled having a RET rearrangement. The phase 1 trial that evaluated the BLU-667 agent, showed a response rate of 58% among 48 patients enrolled. These are promising results.

Having more specific treatment options for patients is good news because those treatments can increase survival and improve the patients’ quality of life. One of the main challenges is having enough patients with the required mutations to evaluate data in clinical trials, but once the treatments become available to the public, they can certainly help a lot of patients.