Written By: Luis E. Raez, MD, FACP
Memorial Healthcare System
Description: The purpose of this PQI is to evaluate the use of lurbinectedin for the treatment of adult patients with metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy.
Background: Small cell lung cancer (SCLC), which accounts for around 15% of all lung cancer diagnoses, is typically highly aggressive with poor survival outcomes.1 The recommended first-line treatment is a platinum-based chemotherapy regimen.3 Few options exist for treatment of patients with SCLC after failure of first-line treatment. Lurbinectedin is an alkylating agent that inhibits oncogenic transcription, approved as second-line therapy in patients with metastatic SCLC. The United States Food & Drug Administration approval of lurbinectedin in this setting is based on a single-arm, open-label, phase 2, multi-centered basket trial in Europe and the US.2 Patients enrolled in the trial were adults (aged ≥18 years) with a pathologically proven diagnosis of SCLC, ECOG performance status ≤ 2, measurable disease, absence of brain metastasis, adequate organ function, and pre-treated with only one previous chemotherapy-containing line of treatment. The primary outcome was overall response (ORR) as assessed by the investigators according to RECIST 1.1. In the 105 patients who were enrolled and treated with lurbinectedin, ORR was demonstrated in 37 patients (35.2%; 95% CI 26.2-45.2). The most common grade 3-4 adverse events included hematological abnormalities such as anemia (9%), leucopenia (29%), neutropenia (46%), and thrombocytopenia (7%). Serious treatment-related adverse events occurred in 10% of the patients, of which neutropenia and febrile neutropenia were the most common (5% patients for each). No treatment-related deaths were reported.2,4
- Screen for drug interactions; avoid coadministration with strong/moderate CYP3A inhibitors/inducers
- Recommended dosage is 3.2 mg/m2 administered over 60 minutes. Treatment is given every 21 days until disease progression or unacceptable toxicity
- No initial dose adjustment recommended for baseline renal or hepatic impairment (limited data available)
- Initiate treatment only if baseline ANC ≥ 1,500 cells/mm3 and platelet count is ≥ 100,000/mm3
- Lurbinectedin is available as a single-dose, preservative free vial with 4 mg lyophilized powder per vial
- Pre-medications for antiemetic prophylaxis:
- Corticosteroids (dexamethasone 8 mg intravenously or equivalent)
- Serotonin antagonists (ondansetron 8 mg intravenously or equivalent)
- Inject 8 mL of SWFI into the vial, yielding a solution containing 0.5 mg/mL lurbinectedin
- Shake the vial until complete dissolution. The reconstituted solution is a clear, colorless or slightly yellowish solution, essentially free of visible particles
- Calculate the required volume of reconstituted solution as follows: Volume (mL) = Body Surface Area (m2) x Individual Dose (mg/m2)/0.5 mg/mL
- Withdraw the appropriate amount of reconstituted solution from the vial and add to an infusion container containing at least 100 mL of diluent (0.9% Sodium Chloride or 5% Dextrose)
Patient Centered Activities:
- Counsel patient on lurbinectedin
- Ensure patient has access to supportive medications: Supply patient with as needed antiemetic medication prescriptions to be used at home
- Instruct patient to report any adverse events, such as diarrhea, nausea/vomiting, mouth sores, or inflammation
Medication Access Assistance
1-833-533-JAZZ (5299) Monday-Friday, 8 AM-8 PM ET
Cautions & Warnings
- Myelosuppression: Monitor blood counts prior to each administration. Withhold, reduce the dose, or permanently discontinue lurbinectedin based on severity. For neutrophil count less than 500 cells/mm3 or any value less than lower limit of normal, the use of myeloid growth factor (G-CSF) is recommended.
- Hepatotoxicity: Monitor liver function tests prior to initiating, periodically during treatment and as clinically indicated. Withhold, reduce dose, or permanently discontinue 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.
Most common adverse reactions (≥20%): 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.
Dose Reduction for Lurbinectedin for Adverse Reactions
- 1st dose reduction – 2.6 mg/ m2 every 21 days
- 2nd dose reduction – 2 mg/m2 every 21 days
- Permanently discontinue if unable to tolerate 2 mg/m2 or dose delay greater than two weeks
|Adverse Reaction||Severity||Dose Modification|
|Neutropenia||Grade 4 or any grade febrile neutropenia||Hold until ≤ Grade 1|
Resume at reduced dose
|Thrombocytopenia||Grade 3 with bleeding or Grade 4||Hold until platelets ≥ 100,00/mm3|
Resume at reduced dose
|Hepatotoxicity||Grade 2/3/4||Hold until ≤ Grade 1|
Resume at reduced dose
- Basumallik N, Agarwal M. Small Cell Lung Cancer. 2021 Jul 17. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan–. PMID: 29494065.
- Trigo J, Subbiah V, Besse B, et al. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial. Lancet Oncol. 2020;21(5):645-654.
- Small Cell Lung Cancer. Version 1.2021. National Comprehensive Cancer Network. Available at: http://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf. Accessed 2021.
- Singh S, Jaigirdar AA, Mulkey F, et al. FDA Approval Summary: Lurbinectedin for the Treatment of Metastatic Small Cell Lung Cancer. Clin Cancer Res. 2021;27(9): 2378-2382.