Recently approved by the Food and Drug Administration (FDA) to treat adult patients with metastatic RET fusion-positive non-small cell lung cancer (NSCLC), Gavreto (pralsetinib) demonstrated efficacy in patients who were not previously treated and in patients who previously received platinum-based chemotherapy.
According to the National Cancer Institute, the RET gene creates a protein that contributes to cell growth, but when mutated, the gene may cause abnormal cells, such as cancer cells, to grow.
“We now appreciate that non-small cell lung cancer is really a family of related but biologically distinct cancers that are the result of unique changes in the DNA of lung cells. These DNA changes include specific mutations and fusions, also known as chromosomal rearrangements,” Dr. Stephen Liu, thoracic medical oncologist and director of thoracic oncology and developmental therapeutics at the Lombardi Comprehensive Cancer Center of Georgetown University, said in an interview with CURE®. “It is very important that all patients with lung cancer undergo proper biomarker testing because these DNA changes help determine the most effective treatment. When testing reveals a RET fusion, which occurs in about 1% to 2% of cases, it directs us toward RET-targeted therapy and away from immunotherapy, which is generally less effective for this type of lung cancer.”
Previous treatment for patients with metastatic RET fusion-positive NSCLC included chemotherapy, immunotherapy or a combination of both treatments, Liu explained. However, he emphasized that these previous treatments had disappointing results.
Now, there is a more effective treatment option after the recent FDA approval of Gavreto, a RET inhibitor, for patients with metastatic RET fusion-positive NSCLC.
“Prior targeted agents were not selective for RET, which increased side effects and limited use. Newer selective RET inhibitors, like Gavreto, are much better tolerated and are the preferred initial therapy when a RET fusion is detected,” Liu said.
Gavreto provides patients with a more effective treatment option, as this targeted option specifically for metastatic RET fusion-positive NSCLC is both highly effective and very well-tolerated, Liu explained. Compared with treatments like chemotherapy and immunotherapy, Liu confirmed that the once daily oral medication of Gavreto is more effective and can lead to “deep and durable responses.”
Regarding side effects that arise with Gavreto, Liu stated that they are easily manageable. “Some patients can develop high blood pressure or leg swelling and it can also lead to a reduction in the white blood cell count,” said Liu. “Monitoring for these (side) effects is straightforward and involves clinic visits and lab tests. Importantly, side effects from RET inhibitors and many other types of targeted therapy are increased when given after immunotherapy — another reason to start with targeted therapy.”
Although Gavreto is already demonstrating a significant change for the better in patients with metastatic RET fusion-positive NSCLC, there are still some unmet needs to be addressed. Liu noted that because selective RET inhibitors are considered the preferred initial treatment for advanced, stage 4 disease, the means to improve outcomes for patients with earlier stages is an unmet need.
“While initial response is seen in the vast majority of patients, overcoming eventual acquired resistance is an important clinical need,” Liu said.
Liu advised that the most important thing to do is to ensure each type of lung cancer in patients is properly tested for the presence of therapeutic targets with next generation sequencing. He noted that it is preferable, if patients are able, to wait for biomarker results before beginning immunotherapy treatment.
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