Clinical Practice Points
- •Lurbinectedin is an intravenous alkylating drug approved by the U.S. Food and Drug Administration (FDA) under accelerated approval on June 15, 2020, for the treatment of adult patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy.
- •During routine pharmacovigilance monitoring, the FDA identified safety signals for new adverse events (AE)s with lurbinectedin: extravasation, rhabdomyolysis, and tumor lysis syndrome (TLS).
- •Further evaluation of these AEs led to their addition to the lurbinectedin U.S. prescribing information (USPI).
- •Clinicians should be aware of these safety issues and implement mitigation strategies to minimize the potential risk of these AEs.
Keywords
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Zepzelca (lurbinectedin) [prescribing information]. Palo Alto, CA: Jazz Pharmaceuticals; 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/213702s004lbl.pdf.
Questions and Answers on FDA's Adverse Event Reporting System (FAERS). Available at: https://www.fda.gov/drugs/surveillance/questions-and-answers-fdas-adverse-event-reporting-system-faers. Accessed: May 6, 2022.
MedDRA. Introductory Guide: MedDRA version 24.0. Available at: https://www.meddra.org/how-to-use/support-documentation/english. Accessed: May 6, 2022.
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Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services; 2017. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf.
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Center for Drug Evaluation and Research. Multi-Discipline Review NDA 213702. U.S. Food and Drug Administration. Available at: www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213702Orig1s000MultidisciplineR.pdf. Accessed: 13 April, 2022.
- Preclinical investigations of pm01183 (lurbinectedin) as a single agent or in combination with other anticancer agents for clear cell carcinoma of the ovary.PLoS One. 2016; 11e0151050https://doi.org/10.1371/journal.pone.0151050
- ATLANTIS: a Phase III study of lurbinectedin/doxorubicin versus topotecan or cyclophosphamide/doxorubicin/vincristine in patients with small-cell lung cancer who have failed one prior platinum-containing line.Future Oncol. 2019; 15: 231-239https://doi.org/10.2217/fon-2018-0597
Center for Drug Evaluation and Research. Pharmacology Review NDA 207953. U.S. Food and Drug Administration. Available at: www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207953Orig1s000PharmR.pdf. Accessed: 13 April, 2022
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- Rhabdomyolysis.Chest. 2013; 144: 1058-1065https://doi.org/10.1378/chest.12-2016
- Lurbinectedin (PM01183), an active compound in platinum-resistant/refractory ovarian cancer (PRROC) patients: Results of a two-stage, controlled phase II study.J Clin Oncol. 2014; 32: 5505
Open-Label, Dose-Escalating, Clinical and Pharmacokinetic Phase I Study of Lurbinectedin (PM01183) in Patients With Advanced Acute Leukemia or Relapsed/Refractory Myelodysplastic Syndrome. ClinicalTrials.gov identifier: 01314599. Available at: https://clinicaltrials.gov/ct2/show/study/NCT01314599. Accessed: June 1, 2022.
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- Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial.Lancet Oncol. 2020; https://doi.org/10.1016/S1470-2045(20)30068-1
Protocol to: Phase III Randomized Clinical Trial of Lurbinectedin (PM01183) versus Pegylated Liposomal Doxorubicin or Topotecan in Patients with Platinum-resistant Ovarian Cancer (CORAIL Trial). ClinicalTrials.gov identifier: NCT02421588. Available at: https://clinicaltrials.gov/ProvidedDocs/88/NCT02421588/Prot_000.pdf. Accessed: May 27, 2022.
Protocol to: Phase III Randomized Clinical Trial of Lurbinectedin (PM01183)/Doxorubicin Versus Cyclophosphamide, Doxorubicin and Vincristine (CAV) or Topotecan as Treatment in Patients With Small-Cell Lung Cancer (SCLC) Who Failed One Prior Platinum-containing Line (ATLANTIS). ClinicalTrials.gov identifier: NCT02566993. Available at: https://clinicaltrials.gov/ProvidedDocs/93/NCT02566993/Prot_000.pdf. Accessed: June 1, 2022.
Protocol to: A Multicenter Phase II Clinical Trial of PM01183 in BRCA 1/2-Associated or Unselected Metastatic Breast Cancer. ClinicalTrials.gov identifier: NCT01525589. Available at: https://clinicaltrials.gov/ProvidedDocs/89/NCT01525589/Prot_000.pdf. Accessed: June 1, 2022.
Protocol to: Phase I Multicenter, Open-label, Clinical and Pharmacokinetic Study of PM01183 in Combination With Doxorubicin in Non-heavily Pretreated Patients With Selected Advanced Solid Tumors. ClinicalTrials.gov identifier: NCT01970540. Available at: https://clinicaltrials.gov/ProvidedDocs/40/NCT01970540/Prot_000.pdf. Accessed: June 1, 2022.
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