One of the biggest challenges in treating non-small cell lung cancer (NSCLC) that’s detected at an early stage is preventing it from coming back.
New research shows the targeted therapy selpercatinib (Retevmo®) reduces the risk of recurrence by more than 80% for non-small cell lung cancers with a gene abnormality called a RET gene fusion.
The study, published in the New England Journal of Medicine on May 31, tracked patients with early-stage lung cancer who had the RET gene abnormality. After having surgery and other standard treatments, some patients took selpercatinib, while others took a placebo (a fake pill with no medicine).
The results were striking: Patients with stage 2 or 3A lung cancer who took selpercatinib were 83% less likely to have their cancer come back, get worse, or die compared to those who took the placebo.
“For patients whose cancer is caught early enough to be surgically removed, our goal is to give them the best chance of being cured,” says thoracic medical oncologist Alexander Drilon, MD, Chief of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center (MSK). “This drug could transform the way we treat this group of patients.”
Dr. Drilon was senior author of the paper and led the clinical trial, which was also presented at the American Society of Clinical Oncology (ASCO) Annual Meeting by Jonathan Goldman, MD, of the University of California, Los Angeles.
How was the selpercatinib trial conducted?
The phase 3 trial enrolled patients at 65 centers in 22 countries. It included patients with early-stage cancer (stage 1B to 3A) whose cancer carried a RET gene fusion.
- All patients in the trial had completed standard treatment for non-small cell lung cancer.
- Most had both surgery and chemotherapy.
- 75 patients received selpercatinib and 76 received a placebo.
Across all stages of cancer in the trial, only 6% of those in the selpercatinib group had their cancer come back after two years, compared with 30% of those in the placebo group.
How common are RET gene fusions in lung cancer?
RET gene fusions are rare — found in only 1% to 2% of all NSCLC tumors. “But because lung cancer is so common, this drug still has the potential to help thousands of patients every year,” Dr. Drilon says.
This gene abnormality is more often found in the cancers of people who have never smoked. RET fusions are also more common in people who are younger than typical lung cancer patients. The average age of patients in this trial was 60.
Why is genetic testing for lung cancer important?
A valuable lesson from this trial is that all lung cancer patients should have genetic testing on their tumors as soon as they’re diagnosed — no matter what stage their cancer is. In the past, doctors mainly did genetic tests for patients whose cancer had already spread.
“The results from this trial show something crucial,” says Dr. Drilon. “Patients with early-stage lung cancer can benefit significantly from drugs that target specific genetic changes in their tumors. When these drugs are given after surgery and other treatments, they can help prevent the cancer from coming back.”
Similar results have been seen in patients whose tumors have mutations in other genes, called EGFR and ALK.
“But we can only match patients with these treatments if we test their tumors first,” Dr. Drilon says. “Without genetic testing, we can’t identify who will benefit from these drugs.”
For that reason, MSK performs molecular testing on lung cancer patients whenever possible. These tests are MSK-IMPACT®, which studies tissue from solid tumors, and MSK-ACCESS®, a “liquid biopsy” test that studies tumor DNA in the blood.
How was selpercatinib developed?
MSK researchers have been at the forefront of developing selpercatinib.
The U.S. Food and Drug Administration (FDA) gave it initial approval to treat advanced lung and thyroid cancers with RET gene fusions based on clinical research led by Dr. Drilon and MSK head and neck medical oncologist Eric Sherman, MD. The FDA eventually granted full approval.
Later, the FDA expanded approval to include all types of metastatic tumors with a RET gene fusion and approved its use in patients as young as 2.
Currently, selpercatinib is only approved for advanced cancer that has spread. If the FDA approves it for patients with early-stage lung cancer based on this new trial, many more patients could benefit from the drug — potentially before their cancer has a chance to spread.
What are the side effects of selpercatinib?
Selpercatinib is taken at home as a pill. It does cause side effects in some patients, but they are often easy to tolerate.
In this trial, 67% of patients taking selpercatinib had side effects, compared with 24% who took the placebo. The most common side effect was elevated liver enzymes (a sign of liver stress), but doctors were able to manage this by lowering the drug dose.
What do we still not know about using selpercatinib to treat early-stage cancer?
Researchers followed patients for an average of only about two years. They plan to continue tracking these patients to confirm that their cancer remains in remission.
For now, many of the patients who benefitted from the selpercatinib trial remain on the treatment. It’s too soon to know whether they will need to stay on it for a specific period, as in this clinical trial, or keep taking it for longer, even indefinitely. “That’s another important question we should study,” Dr. Drilon says.
Key Takeaways
- In a phase 3 trial, the targeted therapy selpercatinib reduced the risk of cancer recurrence, progression, or death by more than 80% in patients with early-stage non-small cell lung cancer harboring a RET gene fusion.
- These findings suggest that genetic testing should be performed on all lung cancer patients at diagnosis, regardless of stage, so they can be matched with targeted treatments that may prevent their cancer from returning.
- Although RET gene fusions occur in only 1% to 2% of non-small cell lung cancers, the large number of lung cancer cases means that selpercatinib could still benefit thousands of patients each year.
- Researchers will continue following trial participants to determine whether selpercatinib’s benefits hold up over the long term and how long patients may need to take the drug.
Additional authors, funding, and disclosures
A full list of study authors is available in the paper.
The trial was funded by Eli Lilly, the manufacturer of selpercatinib.
Dr. Drilon’s disclosures are available on his webpage.