Results from a global phase III clinical trial found that maintenance therapy with a combination of the alkylating agent lurbinectedin and the PD-L1 inhibitor atezolizumab improved survival in some patients with extensive-stage small cell lung cancer (SCLC) compared with maintenance therapy with atezolizumab alone. The research will be presented by Luis G. Paz Ares, MD, PhD, and colleagues at the 2025 ASCO Annual Meeting (Abstract 8006).
“While the introduction of immunotherapy in first-line treatment has improved outcomes, advanced SCLC remains difficult to treat. The phase III IMforte trial shows that the new treatment combination of lurbinectedin and atezolizumab given as maintenance therapy after first-line treatment helps people live longer and reduces the risk of disease progression or death. This outcome represents a major milestone and could provide a much-needed option for advancing the treatment of this aggressive disease,” said lead study author Dr. Paz Ares, of the 12 de Octubre University Hospital in Madrid.
Between 13% and 15% of lung cancer diagnoses are SCLC, the most aggressive type of lung cancer. About 70% of people are diagnosed when SCLC has already spread beyond its site of origin. Advances in treatment for extensive-stage SCLC since 2019 have improved outcomes, but it remains difficult to treat, and the 5-year relative survival rate is 3%, with a median survival time of 1 year.
More on IMforte
The IMforte trial included 660 patients with previously untreated extensive-stage SCLC, no history of metastases to the brain or spinal cord, and a good performance status. All patients enrolled in the study received standard-of-care induction therapy of atezolizumab, carboplatin, and etoposide in four cycles.
After induction therapy, patients were eligible to continue in the study if they had an ongoing tumor response or stable disease after the four cycles. A total of 483 patients went on to receive maintenance therapy; they were randomly assigned to receive either lurbinectedin and atezolizumab (n = 242) or atezolizumab alone (n = 241). The participants were from 91 study sites in 13 different countries; approximately 82% were White, 13% were Asian, 7% were Hispanic or Latino, and 5% had another racial origin. The median age of the participants was 66 years, and approximately 63% of the patients were men.
Key Findings
After a median follow-up of 15 months, the median progression-free survival was 5.4 months with lurbinectedin and atezolizumab vs 2.1 months with atezolizumab alone. Patients treated with lurbinectedin and atezolizumab had a 46% lower risk of disease progression than those treated with atezolizumab alone. The median overall survival was 13.2 months for patients treated with lurbinectedin and atezolizumab and 10.6 months for patients treated with atezolizumab alone. Patients treated with lurbinectedin and atezolizumab had a 27% lower risk of death than those treated with atezolizumab alone.
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.
There was a noted difference in adverse events between the two groups. Treatment-related adverse events occurred in 83.5% of patients in the lurbinectedin and atezolizumab arm compared with 40% in the atezolizumab alone arm. In the lurbinectedin and atezolizumab arm, 25.6% of patients experienced a grade 3 or 4 adverse event, and 0.8% experienced a grade 5 adverse event. In the atezolizumab alone arm, 5.8% experienced a grade 3 or 4 adverse event, and 0.4% experienced a grade 5 adverse event. In the lurbinectedin and atezolizumab arm, 6.2% of patients stopped treatment because of side effects compared with 3.3% in the atezolizumab alone arm.
Next Steps
The IMforte study is ongoing. Researchers will continue to follow enrolled patients. They are also considering other settings in which to use this treatment combination, such as first-line therapy.
ASCO Expert Perspective
“Immunotherapy has improved survival outcomes for patients with extensive-stage SCLC, marking meaningful progress in a historically challenging disease. However, despite these advances, long-term outcomes remain suboptimal, underscoring the need for better strategies. The integration of lurbinectedin—a novel DNA-damaging agent—into the maintenance setting alongside atezolizumab following initial chemoimmunotherapy represents an important next step. This approach offers a way to extend disease control and may signal a shift toward more durable benefit for patients,” said Charu Aggarwal, MD, MPH, FASCO, the Leslye M. Heisler Professor of Medicine at University of Pennsylvania Perelman School of Medicine, and an ASCO expert in lung cancer.
Disclosure: The IMforte study was funded by Genentech. For full disclosures of the study authors, visit coi.asco.org.
