Larotrectinib – Selective TRK Inhibitor for Targeted Cancer Therapy

Larotrectinib is a first-of-its-kind, highly selective oral inhibitor of tropomyosin receptor kinases (TRK). The drug is a unique representative of "agnostic" targeted therapy: its effectiveness does not depend on the type of organ or tissue where the tumor originated, but is determined solely by the presence of a specific genetic defect — an NTRK (Neurotrophic Tyrosine Receptor Kinase) gene fusion. Larotrectinib blocks the activity of chimeric TRK proteins produced as a result of this fusion, which serve as the primary driver for the uncontrolled growth and survival of cancer cells.

The mechanism of action of larotrectinib involves the competitive inhibition of the ATP-binding domain of TRKA, TRKB, and TRKC receptors. When an NTRK gene fusion occurs, these receptors enter a state of constant activation, triggering powerful signaling cascades for proliferation. Larotrectinib effectively "switches off" these signals, leading to rapid tumor regression. NTRK genetic rearrangements are found in a wide spectrum of neoplasms, including rare forms of pediatric cancer (infantile fibrosarcoma) and common adult tumors (lung, thyroid, and colon cancer). The drug demonstrates an unprecedentedly high frequency and duration of response across various age groups, including newborns. A critical characteristic of the substance is its ability to penetrate the central nervous system, allowing it to control both primary brain tumors and metastases.

The drug is available in capsule and oral solution forms. Therapy is only possible after confirmation of an NTRK gene fusion using high-precision genetic testing (NGS).

Wikipedia page
Larotrectinib

Indications

Larotrectinib is indicated for the treatment of adult and pediatric patients with the following disease characteristics:

  • NTRK-positive Solid Tumors: presence of a confirmed NTRK gene fusion without a known acquired resistance mutation.
  • Advanced Disease: treatment of locally advanced or metastatic tumors where surgical resection is likely to result in severe morbidity.
  • Lack of Alternatives: situations where the disease has progressed following standard treatment or where no satisfactory alternative standard therapies are available.

Dosage and administration

The dose of larotrectinib is calculated based on the patient's age and body surface area.

  • Adults and Pediatrics (weight 50 kg or more): the standard dose is 100 mg twice daily.
  • Pediatrics (weight less than 50 kg): the dosage is calculated as 100 mg per square meter of body surface area twice daily.
  • Administration Method: capsules or solution are taken orally twice daily, regardless of food intake. Capsules must not be opened or chewed.
  • Dose Adjustment: if side effects occur, the dose is sequentially reduced in three stages; if the patient cannot tolerate the minimum dose, treatment is discontinued.
  • Missed Dose: if there are more than 6 hours until the next dose, the missed dose should be taken. If vomiting occurs after taking a dose, an additional portion is not taken.

Larotrectinib has a favorable safety profile but possesses the following restrictions:

  • Hypersensitivity: severe allergic reaction to larotrectinib or any auxiliary components (such as sorbitol in the solution).
  • Pregnancy: data on the effect on the fetus are limited, but preclinical studies indicate potential risk; use is not recommended.
  • Lactation: breastfeeding should be discontinued during therapy and for three days after the last dose.
  • Severe Hepatic Impairment: requires a 50% reduction in the starting dose and continuous medical supervision.
  • Drug Interactions: concomitant use of strong CYP3A4 inhibitors or inducers (e.g., St. John's wort or grapefruit juice) should be avoided.

The side effects of larotrectinib are usually mild or moderate. These include:

  • Neurological Reactions: dizziness, gait disturbance (ataxia), and paresthesia (tingling sensation).
  • Hepatobiliary System: increased serum transaminase levels (ALT and AST), which require regular monitoring.
  • Digestion: nausea, vomiting, constipation, or diarrhea, as well as changes in taste perception.
  • Hematology: anemia and a decrease in neutrophil count (neutropenia).
  • General Condition: fatigue, weakness, and moderate weight gain.
  • Muscular System: muscle pain and spasms, sometimes accompanied by increased creatine phosphokinase levels.

Frequently Asked Questions

Larotrectinib is a highly selective inhibitor of tropomyosin receptor kinases (TRK). It is one of the first drugs approved under the "tissue-agnostic" principle: it treats a specific genetic alteration—NTRK gene fusion—rather than a specific type of cancer (like lung or breast cancer). If this mutation is found in a tumor of any organ, larotrectinib can be prescribed to block growth signals.
To prescribe larotrectinib, molecular genetic testing of the tumor tissue is mandatory. The test must confirm the presence of an NTRK1, NTRK2, or NTRK3 gene fusion. Without this specific genetic abnormality, the drug will not be effective, as it exclusively targets the proteins resulting from such fusions.
Because TRK receptors play a role in nervous system function, larotrectinib can cause neurological side effects such as dizziness, gait disturbance, tingling in the extremities, or confusion. Most of these symptoms are mild, but if they occur, a physician should be informed immediately to consider a dose adjustment.
Yes, larotrectinib is approved for use in both adults and children (including infants). For ease of use in pediatric practice, it is available as an oral solution in addition to capsules. The dosage for children is calculated individually based on body surface area.
The larotrectinib oral solution should be stored in the refrigerator (at 2–8°C). If a dose is missed and less than 6 hours have passed, take it immediately. If more than 6 hours have passed, skip the missed dose and take the next one at the scheduled time. Never take a double dose to make up for a missed one.

List of medicines by active substance

-11%
Laronib 100 100 mg Everest
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Everest

Laronib 100

Larotrectinib
100 mg 30 capsules
40000₴ 44944₴
-6%
Laronib 25 25 mg Everest
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Everest

Laronib 25

Larotrectinib
25 mg 30 capsules
30562₴ 32360₴
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