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RET-Positive Lung Cancer After Surgery: How to Read Adjuvant Trial Headlines
Adjuvant targeted therapy is given after surgery to lower recurrence risk. Trial results must be read by biomarker, stage, endpoint, and follow-up.
Original commentary from the Cancer Explained editorial team.
Please note: this page is educational only — it is not medical advice, and it does not speculate about anyone’s health beyond reliable public reporting. For questions about your own health, talk with your healthcare team.
What RET-positive means
The RET gene makes a protein involved in cell growth and in the development of nerve cells. NCI notes that changes in the gene can leave that protein overactive, which can drive abnormal cells to grow. Such changes appear in some non-small cell lung cancers and in thyroid cancer.
In lung cancer, the change is usually a fusion. Part of the RET gene joins part of another gene, and the combined piece keeps the growth signal on.
RET fusions are uncommon in lung cancer. Nobody can tell whether a tumor has one by looking at a scan. It takes a molecular test on tumor tissue or, in some cases, on blood. Our page on biomarker testing covers how those tests work.
What is approved today
Selpercatinib, sold as Retevmo, is FDA approved. NCI lists its uses precisely.
- Non-small cell lung cancer with a RET fusion gene that has spread, in adults.
- Medullary thyroid cancer with an abnormal RET gene that has spread, in adults and children age 2 and older.
- Thyroid cancer with a RET fusion gene that has spread.
- Solid tumors with a RET fusion gene that have spread, when the cancer worsened after other treatment or cannot be treated otherwise. NCI notes this last use was granted under accelerated approval, with confirmatory trials still required.
Every one of those says "has spread." None of them covers early-stage lung cancer that has been removed by surgery. That gap is the story.
Adjuvant means something specific
Adjuvant therapy is treatment given after the main treatment to lower the chance the cancer returns. In early lung cancer, the main treatment is usually surgery.
The premise is that a few cancer cells may have escaped before the operation. They cannot be seen or measured. Treatment is given to people who may already be cured, in the hope of helping the subset who are not.
That premise sets the price. Everyone takes the drug and its side effects. Only some of them needed it.
The trial behind the headlines
LIBRETTO-432 is the study testing whether selpercatinib helps in that setting. Its registry record lists the design.
- Phase 3, randomized, double-blind, and placebo-controlled.
- Enrollment of 152 participants.
- Eligible people have stage IB, II, or IIIA non-small cell lung cancer with a confirmed RET fusion.
- All participants must have completed surgery or radiation given with curative intent.
- The primary outcome is event-free survival.
- Participants assigned to placebo may cross over to selpercatinib if their disease returns.
- The study is listed as active but no longer recruiting.
How to read what comes out of it
Event-free survival is not overall survival. It measures time before the cancer returns or another defined event occurs. A drug can delay recurrence without changing how long people live.
Crossover complicates the survival comparison. If people on placebo can switch to the drug when their cancer returns, the two survival curves get harder to separate.
152 people is a small phase 3. That is a consequence of how rare RET fusions are. It also means confidence intervals will be wide.
"Adjuvant" is not "approved." Until a label changes, use after surgery remains investigational.
What stays the same
Surgery, radiation, chemotherapy, and immunotherapy still carry early-stage lung cancer treatment. A targeted drug after surgery would be an addition, and only for the small group whose tumor carries the matching fusion.
Ask about your tumor's testing
- Has my tumor been tested for RET, and what did the report say?
- Am I eligible for a trial in the adjuvant setting?
- What is the measured outcome, and what does it mean for me?
- What side effects would I take on, and for how long?
- What is my recurrence risk without this treatment?
How this article was prepared
An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.
The National Cancer Information Foundation publishes Cancer Explained. This page is for learning. It is not medical advice and does not suggest a test or treatment.
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Put the story in context
Prevention, possible warning signs, screening, and diagnosis
This story relates to RET-positive lung cancer. The information below is general: it does not reveal anything else about a public person’s health, and not every point applies to every cancer. Personal advice depends on age, symptoms, family history, exposures, and medical history.
Prevention and risk reduction
Not every cancer can be prevented. Avoiding tobacco, protecting skin from ultraviolet radiation, limiting alcohol, staying active, and receiving recommended HPV or hepatitis B vaccination can lower the risk of certain cancers. A risk factor is not a prediction or a cause in one individual.
Symptoms and possible early signs
Possible signs vary and are often caused by conditions other than cancer. Changes worth discussing include a new lump, unexplained bleeding or weight loss, a persistent cough, lasting bowel or bladder changes, a changing skin spot, or symptoms that persist or worsen. Some early cancers cause no symptoms.
Screening and early detection
Screening looks for certain cancers before symptoms begin. Recommended tests exist only for some cancers and depend on age and risk. Screening can have benefits and harms; it is not the same as evaluating a new symptom, and there is no single routine scan or blood test that reliably screens for every cancer.
How cancer is diagnosed
Diagnosis may involve a history and exam, imaging, laboratory tests, and often a biopsy. Pathology can identify the cancer type and may test biomarkers that guide treatment. Symptoms, screening results, tumor markers, or online stories alone cannot confirm cancer.
Learn about this story’s cancer topic
A public story may encourage questions, but it should not be used to estimate your risk or choose testing. Contact a healthcare professional about a persistent or concerning change. Seek urgent care for severe or rapidly worsening symptoms.