Maintenance treatment with the alkylating agent lurbinectedin plus the monoclonal antibody atezolizumab significantly improved both progression-free survival and overall survival compared with atezolizumab alone in patients with extensive-stage small cell lung cancer (SCLC), according to data presented at a press briefing ahead of the 2025 ASCO Annual Meeting.¹

At a median follow-up of 15 months, median progression-free survival more than doubled from 2.1 months with atezolizumab alone to 5.4 months with the combination therapy (hazard ratio [HR] = 0.54; P < .0001), and median overall survival improved from 10.6 months with atezolizumab alone to 13.2 months with the combination therapy (HR = 0.73; P = .0174).

“This study supports the potential for this combination [lurbinectedin plus atezolizumab] to become a new standard of care for this aggressive disease.”

— Luis Paz-Ares, MD, PhD

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“IMforte demonstrated a clinically meaningful and statistically significant improvement in progression-free and overall survival for patients treated with maintenance lurbinectedin plus atezolizumab compared with atezolizumab alone,” said lead study author Luis Paz-Ares, MD, PhD, Chair of Medical Oncology at Hospital Universitario 12 de Octubre in Madrid. “This study supports the potential for this combination to become a new standard of care for this aggressive disease.”

As Dr. Paz-Ares reported, extensive-stage SCLC remains among the most aggressive types of lung cancer, typically diagnosed at an advanced stage. Approximately 70% of patients with SCLC are initially diagnosed with extensive-stage disease. Although initial treatment combining platinum-based chemotherapy with immune checkpoint inhibitors has improved response rates, outcomes remain poor, with rapid disease progression and limited long-term survival.

IMforte Study Design

The IMforte study was designed to investigate whether the addition of lurbinectedin, a novel alkylating agent and transcription inhibitor, could enhance outcomes when combined with the PD-L1 inhibitor atezolizumab as maintenance therapy after induction chemotherapy. Preclinical studies suggested synergy between lurbinectedin and PD-L1 inhibition, supporting the rationale for this combination.

The trial enrolled 660 treatment-naive patients with extensive-stage SCLC who received four induction cycles of atezolizumab, carboplatin, and etoposide. After induction therapy, 483 eligible patients who had achieved either stable disease or a response were randomly assigned 1:1 to receive maintenance treatment with either lurbinectedin plus atezolizumab or atezolizumab alone, administered every 3 weeks until disease progression, unacceptable toxicity, or patient withdrawal. Patients were stratified by the presence of liver metastases, prior prophylactic cranial irradiation, Eastern Cooperative Oncology Group performance status, and baseline lactate dehydrogenase levels.

Survival Outcomes

At a median follow-up of 15 months, median progression-free survival significantly improved from 2.1 months with atezolizumab alone to 5.4 months with the combination (hazard ratio [HR] = 0.54; P < .0001). This translated to a 46% reduction in the risk of disease progression.

Furthermore, median overall survival was extended from 10.6 months with atezolizumab alone to 13.2 months with the combination therapy (HR = 0.73; 95% confidence interval = 0.57–0.95; P = .0174). The median treatment duration was 4.1 months on lurbinectedin and 4.2 months on atezolizumab in the lurbinectedin and atezolizumab arm. In the atezolizumab alone arm, it was 2.1 months.

Treatment-Related Toxicity

Safety data revealed a predictable increase in treatment-related adverse events in the combination arm. Overall, treatment-related adverse events occurred in 83.5% of patients receiving lurbinectedin plus atezolizumab compared with 40.0% of those receiving atezolizumab alone. Grade 3 or 4 treatment-related adverse events were seen in 25.6% vs 5.8% of patients, respectively. Treatment discontinuation from adverse events was reported in 6.2% of the combination group vs 3.3% of the monotherapy group. Grade 5 treatment-related adverse events occurred in two patients (0.8%) in the combination arm (sepsis, febrile neutropenia) and one patient (0.4%) in the control arm (sepsis).

Of note, myelosuppression was more common with the combination but was reported to be manageable, with febrile neutropenia reported in 1.7% of patients. The rate of severe infection was similar between groups.

“Although there was an expected increase in side effects with the addition of lurbinectedin,” said Dr. Paz-Ares, “these events were manageable with prophylactic measures and did not significantly increase treatment discontinuation rates.”

According to Dr. Paz-Ares, future research is needed to further explore biomarkers predicting response to lurbinectedin plus atezolizumab, optimize patient selection, and investigate potential combination strategies to enhance efficacy in this patient population. 

DISCLOSURE: Dr. Paz-Ares reported no conflicts of interest.

REFERENCE

1. Paz-Ares LG, Borghaei H, Liu SV, et al: Lurbinectedin + atezolizumab as first-line maintenance treatment in patients with extensive-stage small cell lung cancer: Primary results of the phase 3 IMforte trial. 2025 ASCO Annual Meeting. Abstract 8006. Presented at press briefing May 21, 2025.

EXPERT POINT OF VIEW

Catherine Meador, MD, PhD, Attending Physician at the Center for Thoracic Cancers and Assistant Professor of Medicine at Harvard Medical School, Boston, provided perspective on the IMforte study and its implications for clinical practice. Dr. Meador agreed that the overall survival benefit demonstrated in this trial is clinically meaningful. “Given the overall survival benefit, the addition of lurbinectedin in the maintenance setting is indicated for the right patient,” she told The ASCO Post. “It’s also worth keeping in mind that the study population selected for patients who did well clinically with induction platinum-doublet chemotherapy. That context will help in selecting patients for this treatment regimen moving forward.”

Catherine Meador, MD, PhD

As for the clinical use of lurbinectedin, Dr. Meador explained that although it is already used in later-line settings for extensive-stage small cell lung cancer (SCLC), these findings could shift practice patterns. “Lurbinectedin is commonly used in later-line treatment of extensive-stage SCLC, but these data suggest a potential benefit to moving it up to the maintenance setting of first-line therapy,” she concluded. 

DISCLOSURE: Dr. Meador reported no conflicts of interest.