Adagrasib is an irreversible inhibitor of KRASG12C mutation, indicated for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) with KRASG12C mutation confirmed by FDA-approved testing.

Side Effects of Adagrasib

Monotherapy for Non-Small Cell Lung Cancer (NSCLC)

Nausea (70%).

Diarrhea (69%).

Vomiting (57%).

Fatigue (55%).

Musculoskeletal pain (38%).

Lymphopenia (20%).

Decreased hemoglobin (7%).

Increased alanine aminotransferase (4.5%).

Combination Therapy with Cetuximab for Colorectal Cancer (CRC)

Rash (84%).

Nausea (68%).

Diarrhea (65%).

Vomiting (57%).

Fatigue (57%).

Musculoskeletal pain (47%).

Severe Side Effects of Adagrasib

Severe Gastrointestinal Adverse Reactions

In monotherapy: The incidence of severe gastrointestinal bleeding is 3.8% (0.8% being Grade 3 or 4), gastrointestinal obstruction is 1.6% (1.4% being Grade 3 or 4), colitis is 0.5% (0.3% being Grade 3), intestinal obstruction is 0.5%, and stricture is 0.3%.

In combination therapy: The incidence of severe gastrointestinal bleeding increases to 8.5% (1.1% being Grade 3 or 4), and gastrointestinal obstruction is 5.3% (all being Grade 3 or 4).

Risk of Hepatotoxicity

In monotherapy: 32% of patients experience elevated ALT/AST (5% being Grade 3, 0.5% being Grade 4).

The incidence of drug-induced liver injury is 0.3% (0.3% being Grade 3).

Precautions for Adagrasib

Contraindications and High-Risk Populations

Contraindicated in patients with congenital long QT syndrome.

Contraindicated in patients with prolonged QTc interval.

Patients with abnormal liver function require close monitoring.

Drug Interactions

Strong CYP3A4 inducers: Avoid concurrent use.

Strong CYP3A4 inhibitors: Avoid use until adagrasib reaches steady-state concentration (approximately 8 days).

Sensitive CYP3A4 substrates: Avoid concurrent use.

Sensitive CYP2C9 or CYP2D6 substrates: Avoid concurrent use.

P-gp substrates: Avoid concurrent use.

Drugs that prolong QT interval: Avoid concurrent use.

Monitoring Requirements

Regularly monitor electrocardiogram (ECG) and electrolytes before and during treatment.

Monitor liver function monthly before the start of treatment and within 3 months after treatment initiation, and thereafter as clinically needed.

Closely monitor for new or worsening respiratory symptoms.

Clinical Management Recommendations

In case of Grade 3 or 4 gastrointestinal adverse reactions, suspend drug administration until symptoms resolve to ≤ Grade 1 or return to baseline.

When the absolute value of QTc > 500 milliseconds or increases by > 60 milliseconds compared with baseline, suspend drug administration until QTc interval < 481 milliseconds or returns to baseline.

For abnormal liver function, adjust the dose according to the severity of the condition.