Guiding Therapy with Clinical Pearls and Expert Insights

Sacituzumab govitecan-hziy (Trodelvy)

Antibody Drug Conjugate | Antineoplastic Agent

Indications and Usage

  • Metastatic Triple-Negative Breast Cancer (mTNBC): Trodelvy is indicated for unresectable locally advanced or metastatic TNBC in adult patients who have received two or more prior treatments, including at least one for metastatic disease.
  • HR-Positive, HER2-Negative Breast Cancer: It is also indicated for unresectable locally advanced or metastatic hormone receptor-positive and human epidermal growth factor receptor 2-negative breast cancer in patients who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting.
 

Mechanism of Action (MOA)

  • Trodelvy is a Trop-2-directed antibody-drug conjugate that binds to Trop-2-expressing cancer cells and releases SN-38 through a hydrolysable linker. SN-38 interacts with topoisomerase I, preventing the relegation of strand breaks, leading to DNA damage and apoptosis.
 

Administration

  • Dosage: The recommended dose is 10 mg/kg administered as an intravenous (IV) infusion on Days 1 and 8 of a 21-day treatment cycle.
  • Infusion Protocol: Administer the initial infusion over 3 hours. Monitor patients during the infusion and for at least 30 minutes post-infusion for signs of infusion-related reactions.
  • Premedication: Premedication with antipyretics, antihistamines, and antiemetics is recommended to prevent infusion reactions and chemotherapy-induced nausea and vomiting.
 

Adverse Effects and Management

Common Adverse Effects

  • Neutropenia: Severe or life-threatening neutropenia is common. Monitor blood cell counts periodically. Consider granulocyte-colony stimulating factor (G-CSF) for secondary prophylaxis. Withhold treatment for absolute neutrophil count below 1500/mm³ or neutropenic fever.
  • Diarrhea: Severe diarrhea may occur. Monitor and provide fluid and electrolytes as needed. Initiate loperamide promptly if infectious causes are ruled out. Withhold treatment until diarrhea resolves to ≤ Grade 1 and reduce subsequent doses.
  • Other: Nausea, vomiting, fatigue, alopecia, and hypersensitivity reactions.
 

Dose Modifications

  • Neutropenia:
    • Grade 4 neutropenia ≥7 days: First occurrence, reduce dose by 25% and administer G-CSF; second occurrence, reduce dose by 50% and administer G-CSF; third occurrence, discontinue treatment.
    • Grade 3-4 neutropenia delaying dosing beyond 3 weeks: Discontinue treatment and administer G-CSF.
  • Non-Hematologic Toxicity:
    • Grade 4 toxicity: First occurrence, reduce dose by 25%; second occurrence, reduce dose by 50%; third occurrence, discontinue treatment.
    • Grade 3-4 toxicity not recovering to ≤ Grade 1 within 3 weeks: Discontinue treatment.
 

Patient Education and Monitoring

  • Before Treatment: Assess patient’s medical history, including any liver problems, pregnancy status, and concomitant medications. Inform patients about the potential side effects and the importance of reporting any adverse reactions immediately.
  • During Treatment: Monitor vital signs, blood cell counts, and signs of infusion-related reactions. Educate patients on the importance of adhering to scheduled infusions and follow-up appointments.
  • After Treatment: Provide medications to manage side effects and instruct patients to keep track of side effect occurrences and severity. Emphasize the importance of contacting their healthcare provider if severe side effects occur.
 

Special Considerations

  • UGT1A1*28 Allele: Patients homozygous for the UGT1A1*28 allele are at increased risk for neutropenia and anemia. Monitor these patients closely and adjust doses as necessary.
  • Pregnancy and Breastfeeding: Trodelvy can cause fetal harm. Advise women of reproductive potential to use effective contraception during treatment and for 6 months after the last dose. Breastfeeding should be avoided during treatment and for at least 1 month after the last dose.
 

Sequence of Therapies

  • Trodelvy is typically used in the second or later line setting for mTNBC and is often used in place of other standard systemic therapies. Other second or later line systemic therapies could be considered after failure of Trodelvy.
 

notion image
 
notion image

 
Did you find this clinical pearl helpful?