Detailed instructions for Entrectinib/Luo Shengquan

1. Basic information

Entrectinib (Entrectinib) is an oral small molecule tyrosine kinase inhibitor that can target multiple fusion genes such as ROS1, NTRK and ALK. It is one of the internationally representative "precision treatment across cancer types" drugs. It is not only used in the field of lung cancer, but also brings new treatment options to rare NTRK gene fusion tumors.

2. Scope of indications

1. ROS1-positive non-small cell lung cancer (NSCLC): It is suitable for adult patients with metastatic NSCLC who are positive for ROS1 gene rearrangement. It provides a more precise and effective solution in addition to traditional chemotherapy.

1. NTRK fusion-positive solid tumors: broader indication coverage, including adults and children over 1 month old. The main groups of people are:

Confirmed by testingNTRK fusion, and no known acquired resistance mutations;

The tumor is metastatic or cannot be surgically removed due to complex anatomical location;

Entrectinib becomes a new option when previous treatments fail or there is a lack of alternative treatments.

3. Usage and dosage

1. Preparation before medication: Gene fusion status needs to be confirmed through tumor tissue or plasma testing. If tissue specimens are difficult to obtain, plasma testing may be used as an alternative. Cardiac function, serum uric acid, QT interval, and electrolyte levels also need to be assessed before treatment.

2. Recommended dose: Adults and those with body surface area ≥1.5m²: Take 600mg orally daily until disease progression or intolerance. Pediatric patients: The dose is adjusted based on body surface area, and the minimum dose can be as low as 250 mg/m².

3. Dosage form and administration method: The capsules can be swallowed whole, or made into an oral suspension for patients who cannot swallow capsules; the suspension must be taken within 2 hours after preparation, and should be discarded after the time is exceeded; the granules can be mixed with soft foods such as yogurt or applesauce, but they must not be used for tube feeding or self-prepared suspensions.

4. Dose adjustment: If adverse reactions occur, graded reduction is usually adopted: first to two-thirds of the original dose, and then to one-third. If it is still intolerable after two dose reductions, the drug should be discontinued.

4. Overview of adverse reactions

Common adverse events include fatigue, constipation, taste changes, edema, dizziness, diarrhea, nausea and joint pain, and some patients may experience cognitive decline or weight gain. More serious conditions include pneumonia, dyspnea, pleural effusion, sepsis or pulmonary embolism, which often require emergency treatment. Patients need to be followed up regularly during medication to identify and deal with related problems as early as possible.

5. Storage and supply

Enrectinib capsules need to be stored in an environment of 20°C to 25°C, and short-term fluctuations of 15°C to 30°C are acceptable. Must keep original packaging and avoid moisture. If it is prepared as a suspension, it should be taken within 2 hours. It must be discarded after the time limit to ensure efficacy and safety.

6. Mechanism of action

Enrectinib blocks abnormal signal transmission in cancer cells by inhibitingTRKA, TRKB, TRKC, ROS1, ALK and other kinase pathways. Many tumors carrying these fusion genes rely on the continued activation of downstream pathways to maintain growth and division, and entrectinib can cut off this key link, thereby inhibiting tumor progression. Its main metabolite M5 has an in vitro activity close to that of the original drug and maintains efficient inhibition of the target.

In animal experiments, entrectinib has shown good penetration into the central nervous system and can exert anti-cancer effects in intracranial tumor models, which also explains its efficacy advantages in patients with brain metastases.

Reference materials:https://www.roche.com/products/rozlytrek