Zepzelca (lurbinectedin) in combination with Tecentriq (atezolizumab) or Tecentriq Hybreza (atezolizumab and hyaluronidase-tqjs) for extensive-stage small cell lung cancer

Initial US Approval:

2020

Key Clinical Studies:

IMforte (NCT05091567)

Drug Class/Description:

Alkylating agent

Indications and Usage:

ZEPZELCA is an alkylating drug indicated:

• in combination with atezolizumab or atezolizumab and hyaluronidasetqjs, for the maintenance treatment of adult patients with extensive-stage small cell lung cancer whose disease has not progressed after first-line induction therapy with atezolizumab or atezolizumab and hyaluronidasetqjs, carboplatin and etoposide. 
• For the treatment of adult patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy.

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 a confirmatory trial(s). 

Dosage and Administration:

• Recommended Dosage: 3.2 mg/m² administered intravenously every 21 days until disease progression or unacceptable toxicity. 
• Administration via a central venous line is recommended to reduce the risk of extravasation that can cause tissue necrosis requiring debridement
• Administer ZEPZELCA as an intravenous infusion over 60 minutes.
• To reduce the risk of nausea, administer corticosteroids and serotonin agonists prior to Cycle 1 and consider use for subsequent cycles.
• To reduce the risk of febrile neutropenia during treatment with ZEPZELCA in combination with atezolizumab or atezolizumab and hyaluronidase-tqjs, administer granulocyte colony-stimulating factor (G-CSF) [Refer to Prescribing Information].   
• Moderate Hepatic Impairment: Recommended dosage is 1.6 mg/m² administered intravenously every 21 days until disease progression or unacceptable toxicity.
• Severe Hepatic Impairment: Avoid use of ZEPZELCA. If use cannot be avoided, the recommended dosage is 1.6 mg/m² administered intravenously every 21 days until disease progression or unacceptable toxicity. 

Dosage Forms and Strengths:

For injection: 4 mg lyophilized powder in a single-dose vial.

Contraindications:

None.

Warnings and Precautions:

• Myelosuppression: Monitor blood counts prior to each administration. Initiate treatment with ZEPZELCA only if baseline neutrophil count is ≥ 1,500 cells/mm³ and platelet count is ≥ 100,000/mm³. For neutrophil count less than 500 cells/mm³ or any value less than lower limit of normal, administer G-CSF. Withhold, reduce the dose, or permanently discontinue ZEPZELCA based on severity.
• Hepatotoxicity: Monitor liver function tests prior to initiating ZEPZELCA, periodically during treatment and as clinically indicated. Withhold, reduce the dose, or permanently discontinue ZEPZELCA based on severity.
• Extravasation Resulting in Tissue Necrosis: Consider use of a central venous catheter to reduce the risk of extravasation. Monitor patients for signs and symptoms of extravasation during the ZEPZELCA infusion. If extravasation occurs, immediately discontinue the infusion, remove the infusion catheter, and monitor for signs and symptoms of tissue necrosis.
• Rhabdomyolysis: Monitor creatine phosphokinase (CPK) prior to initiating ZEPZELCA and periodically during treatment as clinically indicated. Withhold, reduce the dose, or permanently discontinue ZEPZELCA based on severity.
• Embryo-Fetal Toxicity: Can cause fetal harm. Advise females and males of reproductive potential of the potential risk to a fetus and to use an effective method of contraception.

Adverse Reactions:

The most common adverse reactions for ZEPZELCA as a single agent, including laboratory abnormalities, (≥ 20%) are leukopenia, lymphopenia, fatigue, anemia, neutropenia, increased creatinine, increased alanine aminotransferase, increased glucose, thrombocytopenia, nausea, decreased appetite, musculoskeletal pain, decreased albumin, constipation, dyspnea, decreased sodium, increased aspartate aminotransferase, vomiting, cough, decreased magnesium and diarrhea.

The most common adverse reactions, for ZEPZELCA in combination with atezolizumab including laboratory abnormalities, (≥ 30%) are: decreased lymphocytes, decreased platelets, decreased hemoglobin, decreased neutrophils, nausea, and fatigue/asthenia. 

Drug Interactions:

Effect of Other Drugs on ZEPZELCA: Avoid coadministration with strong or a moderate CYP3A inhibitors and strong CYP3A inducers.

Use in Specific Populations:

• Lactation: Advise not to breastfeed. 
• Hepatic Impairment: Avoid use of ZEPZELCA in patients with severe hepatic impairment. In patients with moderate hepatic impairment, reduce the dose of ZEPZELCA. 

Adapted From:

https://pp.jazzpharma.com/pi/zepzelca.en.USPI.pdf

 

Every health-care provider should make their own determination regarding specific safe and appropriate patient care practices, including drug dosages and indications. The provider should always consult the most recent prescribing/product information. FDA Focus information is not guaranteed to be accurate, complete, or current. JADPRO and its editors, authors, reviewers, and commentators cannot be held responsible for any liability incurred as a consequence of the application of any of the information listed within.