Pralsetinib is an oral, highly selective, and potent RET inhibitor.

1. Indications and efficacy

Pranlukast is a selective RET kinase inhibitor, suitable for the following conditions:

RET fusion-positive non-small cell lung cancer (NSCLC): Treatment for adult patients with metastatic RET fusion-positive NSCLC identified through FDA-approved testing

RET fusion-positive thyroid cancer: treatment for patients aged 12 and above with advanced or metastatic RET fusion-positive thyroid cancer who require systemic treatment and are refractory to radioactive iodine (if radioactive iodine is applicable)

This drug blocks the tumor growth signaling pathway by inhibiting RET fusion proteins and activating mutations. The indication for thyroid cancer was granted accelerated approval based on overall response rate and duration of response, and subsequent confirmatory trials are needed to confirm the clinical benefit.

II. Usage and Dosage Specification

Standard dose: 400mg orally once daily for adults and adolescents aged ≥12 years, taken on an empty stomach (fasting from 2 hours before to 1 hour after meals)

Dose adjustment: Gradually reduce the dosage to 300mg, 200mg, or 100mg once daily based on the severity of adverse reactions

Handling of missed doses: If a dose is missed on the same day, it can be taken as soon as possible, and the normal medication schedule can be resumed the next day; no need to take a missed dose after vomiting

Surgical management: Discontinue medication for at least 5 days before elective surgery, and resume medication after at least 2 weeks post-major surgery and once the wound has healed

III. Side effects and precautions

Common adverse reactions (≥25%):

Musculoskeletal pain, constipation, hypertension, diarrhea, fatigue, edema, fever, and cough

Grade 3-4 laboratory abnormalities include lymphopenia, neutropenia, decreased hemoglobin, decreased phosphate, etc

Serious risk warning:

Interstitial lung disease/pneumonia: Incidence rate is 12%, with 3.3% being grade 3-4. In case of respiratory symptoms, discontinue the medication immediately and conduct an evaluation

Hypertension: Incidence rate of 35%, with 18% being Grade 3. Blood pressure needs to be controlled before medication, and regular monitoring during treatment

Hepatotoxicity: AST increased by 49% (grade 3-4: 7%), ALT increased by 37% (grade 3-4: 4.8%). Regular monitoring of liver function is required

Bleeding events: The incidence of grade 3 or above is 4.1%, and severe bleeding requires permanent discontinuation of medication

Wound healing disorders: medication needs to be temporarily suspended before and after surgery

Embryotoxicity: Pregnant women are prohibited from using this product. Patients of childbearing age need to take effective non-hormonal contraceptive measures

IV. Medication for special populations

Children: Applicable to thyroid cancer patients aged ≥12 years, with monitoring of growth plate development required

Liver injury: No dosage adjustment is required for mild to moderate cases, but data is lacking for severe cases

Pregnant women: Animal experiments have shown teratogenicity, and contraception is necessary during and after medication use

Lactation: Breastfeeding is prohibited during treatment and for 1 week after drug withdrawal

5. Drug interactions

CYP3A/P-gp inhibitors: Strong inhibitors should be avoided in combination, and if necessary, the dosage should be reduced to 200mg once daily

CYP3A inducers: Strong inducers should be avoided in combination. If combination is necessary, increase the dosage to 800mg once daily

VI. Clinical efficacy data

NSCLC: For previously treated patients, ORR is 63% (CR 6%), with a median DOR of 38.8 months; for previously untreated patients, ORR is 78% (CR 7%), with a median DOR of 13.4 months

Thyroid cancer: ORR 89%, median DOR not reached, 100% of patients with response duration ≥6 months

Pralsetinibinformation