Lurbinectedin

Lurbinectedin is indicated 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).

Lurbinectedin is an alkylating drug that binds guanine residues in the minor groove of DNA, forming adducts and resulting in a bending of the DNA helix towards the major groove. Adduct formation triggers a cascade of events that can affect the subsequent activity of DNA binding proteins, including some transcription factors, and DNA repair pathways, resulting in perturbation of the cell cycle and eventual cell death. Lurbinectedin inhibited human monocyte activity in vitro and reduced macrophage infiltration in implanted tumors in mice.

The recommended dosage of Lurbinectedin is 3.2 mg/m² by intravenous infusion over 60 minutes every 21 days until disease progression or unacceptable toxicity.

Initiate treatment with Lurbinectedin only if absolute neutrophil count (ANC) is at least 1,500 cells/mm³ and platelet count is at least 100,000/mm³.

The most common adverse reactions, 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.

Based on animal data and its mechanism of action, lurbinectedin can cause fetal harm when administered to a pregnant woman. There are no available data to inform the risk of lurbinectedin use in pregnant women. There are no data on the presence of lurbinectedin in human milk or its effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions from lurbinectedin in breastfed children, advise women not to breastfeed during treatment with lurbinectedin and for 2 weeks after the last dose.

Myelosuppression: Monitor blood counts prior to each administration. Initiate treatment with lurbinectedin only if baseline neutrophil count is ≥1,500 cells/mm3 and platelet count is ≥100,000/mm3. Withhold, reduce the dose, or permanently discontinue lurbinectedin based on severity.

Hepatotoxicity: Monitor liver function tests prior to initiating lurbinectedin, periodically during treatment and as clinically indicated. Withhold, reduce the dose, or permanently discontinue lurbinectedin 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 lurbinectedin 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 lurbinectedin and periodically during treatment as clinically indicated. Withhold, reduce the dose, or permanently discontinue lurbinectedin 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.

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.