FDA Approves Lurbinectedin/Atezolizumab for ES-SCLC Maintenance

The FDA has approved the combination of lurbinectedin (Zepzelca) and atezolizumab (Tecentriq) or atezolizumab and hyaluronidase-tqjs (Tecentriq Hybrezas) as a first-line maintenance treatment in patients with extensive-stage small cell lung cancer (ES-SCLC) whose disease has not progressed following first-line induction therapy with atezolizumab, carboplatin, and etoposide.¹

The approval is supported by data from the phase 3 IMforte trial (NCT05091567) of lurbinectedin plus atezolizumab, which met both primary end points and demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) compared with atezolizumab monotherapy.

Data from IMforte were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. Following induction therapy, patients who did not have disease progression were randomized to receive lurbinectedin plus atezolizumab or atezolizumab alone. From the point of randomization, the median PFS was 5.4 months for the lurbinectedin plus atezolizumab combination vs 2.1 months for atezolizumab alone (stratified HR, 0.54; 95% CI, 0.43-0.67; P <.0001); the median OS was 13.2 months vs 10.6 months (stratified HR, 0.73; 95% CI, 0.57-0.95; P =.0174). The combination reduced the risk of disease progression or death by 46% and the risk of death by 27% compared with atezolizumab alone.^1-3

Regarding safety, no new or unexpected safety signals were reported.² The most common adverse events (AEs) experienced by at least 10% of those in the lurbinectedin/atezolizumab and atezolizumab-alone arms were nausea (36.4% vs 4.2%), anemia (31.8% vs 6.7%), fatigue (20.2% vs 7.9%), decreased appetite (16.9% vs 6.7%), decreased platelet count (15.3% vs 2.9%), diarrhea (14.0% vs 7.5%), vomiting (13.6% vs 2.5%), asthenia (12.8% vs 6.3%), thrombocytopenia (12.8% vs 1.7%), decreased neutrophil count (12.8% vs 1.3%), constipation (12.0% vs 6.3%), and neutropenia (10.7% vs 1.7%).³

AEs led to dose interruption or modification of any drug for 38.0% of patients in the experimental arm vs 13.8% of those in the control arm, and to discontinuation of any drug for 6.2% and 3.3% of patients, respectively. The rate of serious AEs was higher in the doublet arm than in the monotherapy arm (31.0% vs 17.1%).

“A significant challenge with small cell lung cancer is the high rate of attrition at relapse; many patients, sometimes over half, do not receive further therapy. This is because the cancer often returns very aggressively, leaving patients unfit or unwell for additional treatment. Therefore, there's a critical need to prevent progression and maintain disease control proactively, rather than waiting for relapse. This trial aimed to address this by exploring a maintenance strategy using lurbinectedin. While maintenance strategies are logical, there hadn't been a positive study showing improved survival with such an approach until this trial,” said Stephen V. Liu, MD, chief of the Division of Hematology and Oncology at Georgetown Lombardi Comprehensive Cancer Center, in an interview with Targeted Oncology.

REFERENCES

1. FDA approves lurbinectedin in combination with atezolizumab or atezolizumab and hyaluronidase-tqjs for extensive-stage small cell lung cancer. FDA. October 2, 2025. Accessed October 2, 2025. https://tinyurl.com/2pc8wf2b

2. Zepzelca (lurbinectedin) and Atezolizumab (Tecentriq) combination granted US FDA priority review for first-line maintenance treatment of extensive-stage small cell lung cancer. News release. Jazz Pharmaceuticals plc. June 10, 2025. Accessed September 30, 2025. https://tinyurl.com/4njp2wzn

3. Paz-Ares L, Borghaei H, Liu SV, et al. Lurbinectedin (lurbi) + atezolizumab (atezo) as first-line (1L) maintenance treatment (tx) in patients (pts) with extensive-stage small cell lung cancer (ES-SCLC): primary results of the phase 3 IMforte trial. J Clin Oncol. 2025;43(suppl 16):8006. doi:10.1200/JCO.2025.43.16_suppl.8006