Unlike traditional inhibition that targets the active site of a single kinase, ripretinib modulates the kinase "switch" conformation to suppress aberrant kinase signaling of KIT and PDGFRA, which are closely related to the development and progression of GIST. It can also act on certain primary and secondary resistance mutations. Although the therapeutic effect is significant, patients also need to be aware of its potential multisystem adverse reactions and related medication risks during treatment.
Adverse Reactions of Ripretinib
1. Common Adverse Reactions (Higher Incidence)
These reactions are mostly mild to moderate and mainly involve the following systems:
Skin: Alopecia, palmar-plantar erythrodysesthesia syndrome (PPES), dry skin, pruritus.
General: Fatigue, peripheral edema, asthenia.
Digestive system: Nausea, abdominal pain, constipation, diarrhea, vomiting, stomatitis.
Musculoskeletal: Myalgia, arthralgia, muscle spasms.
Metabolism and nutrition: Decreased appetite, weight loss.
Neurological and cardiovascular: Headache, hypertension, and cardiac dysfunction (the latter requires monitoring).
2. Serious or Clinically Significant Adverse Reactions
Palmar-plantar erythrodysesthesia syndrome (PPES): Manifested as erythema, pain, swelling, and desquamation on the palms and soles.
New primary cutaneous malignancies: Including squamous cell carcinoma, keratoacanthoma, melanoma.
Others: Hypertension, cardiac dysfunction (e.g., heart failure, decreased left ventricular ejection fraction), impaired wound healing, photosensitivity.
3. Laboratory Test Abnormalities
Regular blood tests are required. Common changes include elevated lipase, amylase, creatine phosphokinase (CPK), alanine aminotransferase (ALT), bilirubin, as well as decreased serum phosphorus/calcium, neutropenia, and abnormal coagulation parameters (APTT/INR), etc.

