GAVRETO Safety

GAVRETO offers a well-established safety profile

Thyroid patient safety

Safety of GAVRETO was evaluated in 138 patients with RET-altered thyroid cancer1*

*Includes 19 patients with RET fusion-positive thyroid cancer.

RET+=rearranged during transfection.

Adverse reactions (≥15%) in RET-altered thyroid cancer patients who received GAVRETO in ARROW1

Adverse ReactionsGAVRETO (N=138)*
Grades 1-4 (%)Grades 3-4 (%)
Musculoskeletal
Musculoskeletal pain†420.7‡
Gastrointestinal
Constipation410.7‡
Diarrhea†345‡
Abdominal pain†170.7‡
Dry mouth170
Stomatitis†170.7‡
Nausea170.7‡
Vascular
Hypertension4021‡
General
Fatigue†386‡
Edema†290
Pyrexia222.2‡
Respiratory
Cough†271.4‡
Dyspnea†222.2‡
Nervous system
Headache†240
Peripheral neuropathy†200
Dizziness†190.7‡
Dysgeusia†170
Skin and subcutaneous
Rash†240
Metabolism and nutrition
Decreased appetite150

*Includes 19 patients with RET fusion-positive thyroid cancer.
†For grouped terms, please refer to the U.S. Prescribing Information (USPI).
‡Only includes a Grade 3 adverse reaction.

Clinically relevant adverse reactions in <15% of patients who received GAVRETO included tumor lysis syndrome and increased creatine phosphokinase.

Dose reductions, interruptions, and discontinuations due to adverse reactions while taking GAVRETO1,2

  • 3.6% discontinued due to adverse reactions considered treatment-related by the trial investigator2
  • 9% of patients permanently discontinued GAVRETO due to any adverse reaction1
  • 44% of patients treated experienced dose reductions due to an adverse reaction1
  • 67% of patients treated experienced dosage interruptions due to an adverse reaction1

Select laboratory abnormalities (≥20%) worsening from baseline in patients who received GAVRETO in ARROW1

Laboratory Abnormality§GAVRETO (N=138)*
Grades 1-4 (%)Grades 3-4 (%)
Chemistry
Decreased calcium (corrected)709
Increased aspartate aminotransferase (AST)694.3
Increased alanine aminotransferase (ALT)433.6
Increased creatinine410
Decreased albumin411.5
Decreased sodium282.2
Decreased phosphate288
Decreased magnesium270.7
Increased potassium261.4
Increased bilirubin241.4
Increased alkaline phosphatase221.4
Hematology
Decreased lymphocytes6727
Decreased hemoglobin6313
Decreased neutrophils5916
Decreased platelets312.9
GAVRETO showed Grades 3-4 AST/ALT elevations of 4.3% and 3.6%.1

*Includes 19 patients with RET fusion-positive thyroid cancer.
§Denominator for each laboratory parameter is based on the number of patients with a baseline and post-treatment laboratory value available, which ranged from 135 to 138 patients.

Other clinically relevant laboratory abnormalities in patients who received GAVRETO included increased phosphate (40%).1

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Recommended Dose Modifications
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GAV_THR-25011 0525

References:

 

1. GAVRETO® [Package insert], South San Francisco, CA: Rigel Pharmaceuticals, Inc.

 

2. GAVRETO: Data on file, Rigel Pharmaceuticals, Inc. June 2024.

Indications & Important Safety Information

INDICATIONS

GAVRETO (pralsetinib) is indicated for the treatment of:

  • Adult patients with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA-approved test
  • Adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate)*

*This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

IMPORTANT SAFETY INFORMATION

Interstitial Lung Disease (ILD)/Pneumonitis: Severe, life-threatening, and fatal ILD/pneumonitis can occur in patients treated with GAVRETO. Pneumonitis occurred in 12% of patients who received GAVRETO, including 3.3% with Grade 3-4, and 0.2% with fatal reactions. Monitor for pulmonary symptoms indicative of ILD/pneumonitis. Withhold GAVRETO and promptly investigate for ILD in any patient who presents with acute or worsening of respiratory symptoms (e.g., dyspnea, cough, and fever). Withhold, reduce dose or permanently discontinue GAVRETO based on severity of confirmed ILD.

Hypertension: Occurred in 35% of patients, including Grade 3 hypertension in 18% of patients. Overall, 8% had their dose interrupted and 4.8% had their dose reduced for hypertension. Treatment-emergent hypertension was most commonly managed with anti-hypertension medications. Do not initiate GAVRETO in patients with uncontrolled hypertension. Optimize blood pressure prior to initiating GAVRETO. Monitor blood pressure after 1 week, at least monthly thereafter and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue GAVRETO based on the severity.

Hepatotoxicity: Serious hepatic adverse reactions occurred in 1.5% of patients treated with GAVRETO. Increased aspartate aminotransferase (AST) occurred in 49% of patients, including Grade 3 or 4 in 7% and increased alanine aminotransferase (ALT) occurred in 37% of patients, including Grade 3 or 4 in 4.8%. The median time to first onset for increased AST was 15 days (range: 5 days to 2.5 years) and increased ALT was 24 days (range: 7 days to 3.7 years). Monitor AST and ALT prior to initiating GAVRETO, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce dose or permanently discontinue GAVRETO based on severity.

Hemorrhagic Events: Serious, including fatal, hemorrhagic events can occur with GAVRETO. Grade ≥3 events occurred in 4.1% of patients treated with GAVRETO including one patient with a fatal hemorrhagic event. Permanently discontinue GAVRETO in patients with severe or life-threatening hemorrhage.

Tumor Lysis Syndrome (TLS): Cases of TLS have been reported in patients with medullary thyroid carcinoma receiving GAVRETO. Patients may be at risk of TLS if they have rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration. Closely monitor patients at risk, consider appropriate prophylaxis including hydration, and treat as clinically indicated.

Risk of Impaired Wound Healing: Impaired wound healing can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway. Therefore, GAVRETO has the potential to adversely affect wound healing. Withhold GAVRETO for at least 5 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of GAVRETO after resolution of wound healing complications has not been established.

Embryo-Fetal Toxicity: Based on findings from animal studies and its mechanism of action, GAVRETO can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with GAVRETO and for 2 weeks after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with GAVRETO and for 1 week after the last dose.

Common adverse reactions (≥25%) were musculoskeletal pain, constipation, hypertension, diarrhea, fatigue, edema, pyrexia, and cough. Common Grade 3/4 laboratory abnormalities (≥2%) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased phosphate, decreased leukocytes, decreased sodium, increased aspartate aminotransferase (AST), increased alanine aminotransferase (ALT), decreased calcium (corrected), decreased platelets, increased alkaline phosphatase, increased potassium, decreased potassium, and increased bilirubin.

Avoid coadministration of GAVRETO with strong or moderate CYP3A inhibitors, P-gp inhibitors, or combined P-gp and strong or moderate CYP3A inhibitors. If coadministration cannot be avoided, reduce the GAVRETO dose. Avoid coadministration of GAVRETO with strong or moderate CYP3A inducers. If coadministration cannot be avoided, increase the GAVRETO dose.

Lactation: Advise women not to breastfeed during treatment with GAVRETO and for 1 week after the last dose.

Pediatric Use: Monitor open growth plates in adolescent patients. Consider interrupting or discontinuing GAVRETO if abnormalities occur.

You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please click here to see the full Prescribing Information and Patient Information for GAVRETO.