An overview of lurbinectedin as a new second-line treatment option for small cell lung cancer

Abstract

Small cell lung cancer (SCLC) is a highly proliferative, aggressive form of lung cancer that carries a poor prognosis. Recent approvals with new therapeutic options represent the first in more than a decade for SCLC. Lurbinectedin, a newly approved second-line option, is a synthetic alkaloid that covalently binds DNA, generating double-strand breaks, and disrupts DNA-protein interactions and RNA transcription. Lurbinectedin may also modulate the tumor microenvironment by inducing apoptosis of peripheral blood monocytes and tumor associated macrophages, decreasing expression of the inflammatory chemokine (C-C motif) ligand 2 (CCL2) and reducing tumor angiogenesis. A single-arm, open-label, basket trial included 105 patients with SCLC that had received one prior line of therapy. Patients received lurbinectedin 3.2\u2009mg/m2 as an intravenous infusion every 3\u2009weeks, resulting in a response rate of 35.2% and a disease control rate of 68.6%. The response rate was 45% among those with >90\u2009days chemotherapy free interval (CTFI) and 22% in the resistant group (CTFI\u2009<\u200990\u2009days). The median overall survival was 9.3\u2009months. Myelosuppression is the most frequent clinically significant adverse event, particularly neutropenia; however, neutropenic fever occurred in only 5% of those in the SCLC cohort of the basket trial. Nausea and fatigue were also noted. The side effect profile compares favorably to topotecan, while a direct comparison of tolerability can be made between lurbinectedin versus topotecan or pegylated-liposomal doxorubicin from CORAIL, a randomized study for platinum-resistant/refractory ovarian cancer. A press release has reported the ongoing clinical trial for SCLC including combination lurbinectedin and doxorubicin versus topotecan or cyclophosphamide, doxorubicin, and vinblastine to be negative. The details may provide more insight at publication, and future trials will be important to further define the clinical utility of lurbinectedin. Lurbinectedin represents a new option in second-line SCLC.