NEWS & PERSPECTIVE

Lurbinectedin as a promising new agent for treating metastatic small cell lung cancer

29 Oct 2020

Small cell lung cancer (SCLC) is deadly cancer with a high mortality rate in which most patients will relapse and die of this disease.1 Despite an initial response rate of 80%, SCLC patients who fail the first-line treatment usually progress with a median time to progression of 3.5 months, with limited second-line treatment options available.1 Lurbinectedin is a novel cancer drug that blocks transcription and incudes DNA double-strand breaks that leads to eventual cancer cell apoptosis.1 With an active overall response and an acceptable and manageable safety profile, lurbinectedin could be a potential new treatment for patients with SCLC in the second-line setting where limited options are available in the event of SCLC relapse.1

At diagnosis, SCLC typically comprises of 13-15% of all lung cancer cases.2 In the first-line setting, SCLC is commonly treated with locoregional therapy or systemic chemotherapy, with improved overall survival (OS).2 However, when SCLC relapses, few therapeutic options are available. In fact, topotecan is the only currently approved second-line treatment option for patients with a chemotherapy-free interval of more than 60 days.2 Even then, the use of topotecan has only achieved an approximately 16% response rate and a median OS of 6-8 months while being associated with notable hematological toxiticites.2 To address the unmet need of having more effective and less toxic treatment options for SCLC patients in the second-line setting, lurbinectedin was evaluated for its activity and safety in SCLC patients after failing platinum-based chemotherapy.2

In the single-arm, open-label, phase 2 basket trial, 105 metastatic SCLC patients who had disease progression on or after platinum-based chemotherapy were recruited from 26 hospitals in 6 European countries and the United States.2 Patients were administered lurbinectedin intravenously until disease progression or unacceptable toxicity.2 After a median follow-up of 17.1 months, the overall response rate (ORR) of lurbinectedin was 35.2% (95% CI: 26.2-45.2). The median response duration was 5.3 months (95% CI: 4.1-6.4), and 43% (95% CI: 25.6-60.5) of patients were still responding to treatment after 6 months.2 The median progression-free survival (PFS) was 3.5 months (95% CI: 2.6-4.3), with 46.6% and 32.9% patients achieved 4-month and 6-month PFS.2 The median OS was 9.3 months (95% CI: 6.3-11.8), and 67.1% and 34.2% patients have achieved 6-month and 12-month OS.2

For a safety standpoint, the most notable toxicity was myelosuppression which is reversible. Compared to topotecan, lurbinectedin did not lead to any treatment-related deaths, a lower rate of discontinuation due to toxicity, reduced grade 3-4 anemia, neutropenia, and thrombocytopenia as well as a lower incidence of febrile neutropenia despite primary G-CSF prophylaxis in topotecan treatment.2 Notably, the incidence of febrile neutropenia without primary use of G-CSF was low among the lurbinectedin treated patients.2

Based on the results of this phase 2 study, the United States Food and Drug Administration has granted an accelerated approval to lurbinectedin in treating metastatic SCLC, further supporting the role of lurbinectedin in the treatment of released SCLC patients.3 With an active overall response and an acceptable and manageable safety profile, lurbinectedin could be a potential new treatment option for SCLC patients who have failed first-line platinum-based chemotherapy and protect these patients in the second-line setting where options are limited.


References
  1. Perez J et al. Efficacy and safety of lurbinectedin (PM1183) in small cell lung cancer (SCLC): Results from a phase 2 study. American Society of Clinical Oncology. May 20, 2018; 36(15): 8570-8570
  2. Trigo J et al. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open label, phase 2 basket trial. Lancet Oncology. May 2020; 21(5): 645-654  
  3. The Food and Drug Administration. FDA grants accelerated approval to lurbinectedin for metastatic small cell lung cancer. 2020. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-lurbinectedin-metastatic-small-cell-lung-cancer. Accessed October 5, 2020.  
SCLC
PLATINUM-BASED CHEMOTHERAPY