MHRA Approves Lurbinectedin Plus Atezolizumab as First-Line Maintenance in Extensive-Stage SCLC
核心洞察
The MHRA approved lurbinectedin (Zepzelca) with atezolizumab as maintenance therapy for adults with extensive-stage small cell lung cancer (搜索) whose disease has not progressed after induction chemoimmunotherapy.
The decision rests on the Phase 3 IMforte trial, in which 483 of 660 induction-treated patients were randomized to the combination or atezolizumab alone.
Median overall survival reached 13.2 months with lurbinectedin plus atezolizumab versus 10.6 months with atezolizumab alone, a 27% reduction in death risk.
The Medicines and Healthcare products Regulatory Agency (搜索) approved lurbinectedin (Zepzelca) on 23 September 2026 for adults with extensive-stage small cell lung cancer (搜索) (SCLC), in combination with atezolizumab, as maintenance treatment in patients whose cancer has not progressed following first-line induction therapy with atezolizumab, carboplatin, and etoposide. The marketing authorisation was granted to Pharma Mar, S.A. (搜索)
The approval adds a maintenance option for patients who complete induction chemoimmunotherapy and achieve disease control, a setting where durable disease control remains a clinical challenge. SCLC is an aggressive subtype of lung cancer marked by rapid tumor growth, early metastatic spread, and a high risk of recurrence.
IMforte Trial Design and Efficacy
The decision was supported by the Phase 3 IMforte trial (NCT05091567), a randomized, multicenter study that compared lurbinectedin plus atezolizumab with atezolizumab alone as maintenance therapy. The study enrolled 660 patients who received first-line induction therapy with atezolizumab, carboplatin, and etoposide. Among those whose disease had not progressed, 483 participants were randomized to lurbinectedin plus atezolizumab (242 patients) or atezolizumab alone (241 patients).
Patients receiving the combination lived for a median of 13.2 months, compared with 10.6 months for those receiving atezolizumab alone, corresponding to a hazard ratio of 0.73, or a 27% reduction in the risk of death (p=0.017). Investigator-assessed median progression-free survival was 5.4 months with lurbinectedin plus atezolizumab versus 2.1 months with atezolizumab alone, a hazard ratio of 0.54 representing a 46% reduction in the risk of disease progression or death (p<0.0001).
The IMforte results were published in The Lancet in 2025 (DOI: 10.1016/S0140-6736(25)01011-6).
Safety Profile
The safety profile was consistent with the known characteristics of both therapies. Grade 3-4 adverse events occurred in 38% of patients receiving lurbinectedin plus atezolizumab, compared with 22% of those receiving atezolizumab alone. The most frequently reported severe adverse events in the combination group were hematologic toxicities including anemia, neutropenia, and thrombocytopenia.
The most common side effects reported with lurbinectedin include nausea, fatigue, anaemia, thrombocytopenia, and neutropenia. Patients who experience side effects should speak to their doctor, pharmacist or nurse, and suspected side effects can be reported through the MHRA's Yellow Card scheme.
Julian Beach, MHRA Executive Director of Healthcare Quality and Access, said the approval provides a new treatment option for adults with extensive-stage SCLC whose disease has not progressed following initial treatment with atezolizumab, carboplatin, and etoposide. He added that the agency will continue to monitor the medicine's safety through the UK Yellow Card scheme and encouraged patients and healthcare professionals to report any suspected side effects.
Mechanism and Administration
Lurbinectedin attaches to DNA inside cancer cells, damaging the DNA and interfering with the growth and multiplication of cancer cells, which leads to cancer cell death. It also reduces the activity of certain immune cells that help tumours grow. The synthetic compound targets transcription processes involved in tumor growth, and it affects components of the tumor microenvironment, including tumor-associated macrophages that may support tumor progression.
Atezolizumab is an immune checkpoint inhibitor targeting PD-L1 (搜索). By blocking PD-L1 signaling, it helps restore anti-tumor immune activity and enables T cells to better recognize and attack cancer cells. The combination pairs direct effects on tumor biology with activation of the immune response.
Lurbinectedin is given as an intravenous infusion over one hour, with the recommended dose administered once every 21 days. Treatment should be started and supervised in a hospital or clinic by a healthcare professional.
Regulatory Route
The product was submitted and approved via the International Recognition Procedure Route B, with the European Medicines Agency (搜索) acting as the Reference Regulator. The UK approval follows regulatory decisions in other regions based on the IMforte trial results. The Summary of Product Characteristics and Patient Information leaflets will be published on the MHRA Products website within 7 days of approval.
Despite recent advances, extensive-stage SCLC remains associated with significant unmet medical needs, and researchers continue to investigate strategies combining chemotherapy, immunotherapy, and targeted treatments to improve outcomes.