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FDA Approval: Entrectinib (Rozlytrek) for Cancer
FDA approved Entrectinib (Rozlytrek), a ROS1/NTRK inhibitor, for certain cancers with specific biomarkers. What was approved, the evidence, and what it does and doesn't mean.
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.
An approval defined by a gene, not an organ
Cancer approvals are usually written by body part. Lung. Breast. Colon. On August 15, 2019, the FDA granted accelerated approval to entrectinib, sold as Rozlytrek, using a different rule.
It covers adults and adolescents aged 12 or older who have solid tumors carrying a specific genetic change, whatever organ those tumors started in. NCI calls this a tissue agnostic indication. Entrectinib was the third cancer drug approved on that basis.
The change in question is an NTRK gene fusion. One of the three NTRK genes joins with another gene, and the result is a TRK fusion protein that drives growth. Entrectinib blocks TRK, along with other growth-driving proteins.
Its FDA label carries an Initial U.S. Approval date of 2019.
Who the label covers
The tissue-agnostic use has conditions attached. The cancer must be metastatic and have worsened after systemic treatment, or be locally advanced and impossible to remove by surgery. And the patient must have no other effective treatment options.
On the same day, the FDA also approved entrectinib for adults with non-small cell lung cancer carrying a gene fusion involving ROS1. Entrectinib blocks ROS1 proteins too.
NCI's current listing describes both. For NTRK fusion solid tumors, it now covers adults and children aged 1 month and older, and it notes the tumor must not carry a drug-resistance mutation in certain TRK proteins. That use remains under the FDA's Accelerated Approval Program, with confirmatory trials required.
The evidence, and how small it was
The NTRK approval rested in part on three small trials: ALKA-372-001, STARTRK-1, and STARTRK-2, sponsored by the manufacturer.
Participants had different cancers, mostly sarcoma, lung cancer, and salivary gland cancer, either metastatic or locally advanced. NTRK fusions were identified by a genetic test.
Among the 54 participants with NTRK fusions in the analysis, 31 saw their tumors shrink. That is 57 percent. Four had a complete response, meaning no detectable cancer remained.
The ROS1 lung cancer approval used the same three trials. Among 51 participants with ROS1-fusion NSCLC, tumors shrank in 40, or 78 percent, including 3 complete responses. For more than half of those whose tumors shrank, the response lasted at least 12 months.
Seven of those participants had tumors that had already spread to the brain or spinal cord at study entry. Entrectinib shrank those in five of them. NCI quotes David Hong of M.D. Anderson noting that people with ROS1 fusion lung cancer often develop tumors in the brain or spinal cord, and that targeted therapies and chemotherapy often do not work there.
Fifty-four patients is a very small evidence base for an approval that spans every solid tumor type. That is the trade a tissue-agnostic approval makes, and it is why the confirmatory requirement exists. Our page on clinical trial phases covers how those later studies work.
The side effects that stand out
The most serious side effects across the trials were congestive heart failure, central nervous system effects such as cognitive impairment and dizziness, and bone fractures. The most common were fatigue, constipation, and dysgeusia, meaning a distorted sense of taste.
Children were more likely than adults to have neutropenia, meaning low white cell counts, plus bone fractures and weight gain.
The nervous system effects are not an accident. TRK proteins have important roles in the development and function of the nervous system, so a drug that blocks TRK affects it too.
Why testing decides everything here
Nobody can be considered for this drug without a molecular test result. NTRK fusions are rare across common cancers and more frequent in a few uncommon ones, and they cannot be seen on imaging or on a standard pathology slide.
This is the practical meaning of precision medicine. The question shifts from what organ the cancer is in, to what is driving it. Our pages on biomarker testing and targeted therapy cover how those results are produced and used.
When to get something checked
Because this approval is not tied to one organ, the useful symptom list is the general one. NCI's page on symptoms of cancer names, among others:
- A lump or firm feeling in the breast or under the arm, or nipple changes.
- Trouble or pain passing urine, or blood in the urine.
- Bleeding or bruising for no known reason.
- Blood in the stools, or a change in bowel habits.
- A cough or hoarseness that does not go away.
- Trouble swallowing, ongoing indigestion, belly pain, or appetite change.
- Severe fatigue that lasts.
- Fever or night sweats for no known reason.
- A white or red patch on the tongue or in the mouth.
- Headaches, seizures, vision or hearing changes, or drooping of the face.
- A sore that does not heal, a new or changing mole, or jaundice.
- Swelling or lumps in the neck, underarm, stomach, or groin.
- Weight gain or weight loss for no known reason.
NCI is clear that these can have many causes other than cancer. What earns a visit is persistence.
What tissue-agnostic approvals change
NCI quotes Nita Seibel of NCI's Cancer Therapy Evaluation Program calling the approval good news because it broadens the options available for patients with these fusions. It also quotes Dr. Hong saying tissue-specific therapies are not going away any time soon, but that more tissue-agnostic therapies are coming.
Both statements are worth keeping. A gene-defined approval adds an option for a small group. It does not replace the treatment plans built around cancer type and stage. Our page on what cancer is covers why cancers from different organs can still share a driver.
What this approval cannot tell you
A 57 percent response rate in 54 people is a real signal from a small sample. It is not a survival result, and accelerated approval means the benefit is not yet confirmed. Whether entrectinib fits one person depends on the test result, prior treatments, heart function, other medicines, and tolerance for the nervous system effects.
Sources
- NCI Cancer Currents, FDA approves entrectinib for tumors with NTRK fusions — https://www.cancer.gov/news-events/cancer-currents-blog/2019/fda-entrectinib-ntrk-fusion
- NCI, Entrectinib — https://www.cancer.gov/about-cancer/treatment/drugs/entrectinib
- DailyMed, ROZLYTREK (entrectinib) label, Initial U.S. Approval 2019 — https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c7c71b0c-2549-4495-86b6-c2807fa54908
- NCI, Symptoms of Cancer — https://www.cancer.gov/about-cancer/diagnosis-staging/symptoms
- NCI, What Is Cancer? — https://www.cancer.gov/about-cancer/understanding/what-is-cancer
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 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.
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.