Platinib User Manual: Detailed Introduction, Dosage and Safety Instructions

1. Drug names and aliases:

Pralsetinib, also known asPralsetinib, is a drug marketed under the trade names Gavreto and Phujihua. In addition, it has several other aliases, including prasitinib, prexitinib, and BLU-667.

2. Applicable symptoms

1. Metastatic RET fusion-positive non-small cell lung cancer (NSCLC): Pralsetinib is specifically used to treat metastatic RET fusion-positive non-small cell lung cancer in adult patients.

2. RET fusion-positive thyroid cancer (TC): Platinib is also indicated for patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and have an inadequate response to radioactive iodine therapy (if applicable).

3. Medication Guide:

1. Before starting platinib treatment, patients must be confirmed to have RET gene fusion in their thyroid cancer or non-small cell lung cancer.

2. Dosage: The usual dosage is 400 mg once a day. It is recommended that patients take it orally on an empty stomach, or avoid eating at least 2 hours before taking the medicine and at least 1 hour after taking the medicine. Treatment should be continued until the condition worsens or until intolerable side effects occur.

3. Dosage adjustment: If the patient experiences adverse reactions, the dose should be adjusted under the advice of a doctor. It can be reduced to 300mg per day for the first time, to 200mg per day for the second time, and to 100mg per day for the third time. Patients who cannot tolerate 100 mg daily should permanently discontinue platinib. The dose of platinib may need to be adjusted when used concomitantly with other drugs, such as CYP3A and/or P-gp inhibitors, or strong CYP3A inducers.

(1) When used in combination with CYP3A and/or P-gp inhibitors: 400mg once a day is recommended to be reduced to 200mg; 300mg a day can be reduced to200mg; 200mg a day is recommended to be reduced to 100mg. After 3 to 5 elimination half-lives of discontinuing the inhibitor, reintroduce platinib at the same dose as before starting the combination of P-gp and a strong CYP3A inhibitor.

(2) When coadministered with a strong CYP3A inducer: If coadministration with a strong CYP3A inducer cannot be avoided, increase the starting dose to twice the current dose starting from the 7th day of coadministration of platinib with a strong CYP3A inducer. After discontinuing the inducer for at least 14 days, reinstitute platinib at the same dose as before starting the strong CYP3A inducer.

4. Possible side effects:

In clinical trials, the most common side effects (≥25%) included musculoskeletal pain, constipation, hypertension, diarrhea, fatigue, edema, pyrexia, and cough. At the same time, there are some abnormal laboratory test indicators (≥2%), such as lymphopenia, neutrophil decrease, hemoglobin decrease, phosphate decrease, leukocyte decrease, sodium decrease, aspartate aminotransferase (AST) increase, alanine aminotransferase (ALT) increase, calcium decrease, thrombocytopenia, alkaline phosphatase increase, potassium increase, potassium decrease, bilirubin increase, etc.

5. Storage method:

Platinib should be stored at 20°C to 25°C, with an allowed temperature fluctuation range of 15°C to 30°C. At the same time, pay attention to moisture-proof.

6. Taboos for use:

No clear contraindications to the use of platinib have been identified.

7. Principle of drug action:

Platinib is a kinase inhibitor that targets wild-type RET and oncogenic RET fusions and mutations. In cell experiments, platinib showed strong inhibitory effects onRET, thereby preventing excessive proliferation of tumor cells and driving tumorigenic potential. In addition, it exhibits significant antitumor activity in animal models.

The maximum inhibitory concentration of platinib is less than 0.5nM. In the purified enzyme test, platinib inhibited DDR1, TRKC, FLT3, JAK1-2, TRKA, VEGFR2, PDGFRB and FGFR1 at higher concentrations, which can still reach Cmax clinically. In cell experiments, platinib inhibited RET at concentrations that were 14-fold, 40-fold, and 12-fold lower than VEGFR2, FGFR2, and JAK2, respectively.

8. Precautions for use by special groups:

1. For pregnant women and women of childbearing potential, since Platinib may cause harm to the fetus, it is recommended to use effective non-hormonal contraceptive methods during treatment and within 2 weeks after stopping the drug. At the same time, because platinib may affect the effectiveness of hormonal contraceptives, breastfeeding is not recommended during this period.

2. For male patients of childbearing potential, if their female partners are in the childbearing period, they should also take effective contraceptive measures during treatment and within 1 week after stopping the drug.