Lurbinectedin Plus Atezolizumab Maintenance Shows Improved Survival vs Atezolizumab in SCLC

The phase 3 IMforte trial (NCT05091567) met its primary end points of improved independent review facility–assessed progression-free survival (IRF-PFS) and overall survival (OS) with lurbinectedin plus atezolizumab vs atezolizumab alone in patients with extensive-stage small cell lung cancer (ES-SCLC).¹

Findings from the primary analysis of the open-label, randomized study will be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, which is being held from May 30 to June 3.

In the phase 3 IMforte trial, patients with extensive-stage small cell lung cancer experienced clinically meaningful benefits with maintenance lurbinectedin plus atezolizumab vs atezolizumab. | Image credit: appledesign - stock.adobe.com

Outcomes in ES-SCLC have improved in the era of immunotherapy, but treatments with better long-term efficacy are needed to improve survival in this patient population. The current standard approach is chemotherapy in combination with a PD-L1 inhibitor such as durvalumab or atezolizumab, followed by maintenance therapy with a PD-L1 inhibitor.

“Most of those patients are actually responding to treatment, but treatment response is typically not long-lasting, and after a few months, patients relapse, and second- and third-line treatments are not very effective,” Luis Paz-Ares, MD, PhD, head of medical oncology at the Hospital Universitario 12 de Octubre in Madrid, Spain, and IMforte trial principal investigator, said in a press conference ahead of the meeting.

The IMforte trial assessed the combination of lurbinectedin, a novel alkylating agent and transcription inhibitor, and atezolizumab in the maintenance setting following chemoimmunotherapy.² A total of 660 patients with treatment-naive ES-SCLC, no history of metastases to the brain or spinal cord, and good performance status were enrolled in the study, and 483 were randomized to receive either lurbinectedin plus atezolizumab (n = 242) or atezolizumab (n = 241) following 4 cycles of standard-of-care induction therapy of atezolizumab, carboplatin, and etoposide.

At a median follow-up of 15 months, patients in the combination therapy cohort showed significantly improved IRF-PFS (stratified HR, 0.54; 95% CI, 0.43-0.67; P < .0001) and a significant OS benefit (stratified HR, 0.73; 95% CI, 0.57-0.95; P = .0174) vs those in the atezolizumab cohort. The median duration of maintenance therapy in the lurbinectedin plus atezolizumab cohort was 4.1 months with lurbinectedin and 4.2 months with atezolizumab, compared with 2.1 months in the atezolizumab cohort.

Notably, adverse events (AEs) were significantly more common in the combination therapy cohort vs the atezolizumab-alone cohort. In the lurbinectedin plus atezolizumab cohort, treatment-related AEs (TRAEs) occurred in 83.5% of patients, compared with 40% of patients in the atezolizumab cohort. Additionally, 25.6% vs 5.8% of patients, respectively, experienced grade 3 or 4 TRAEs.

“Altogether, I think we saw side effects that had no new signals, and there was an increase in the number of side effects, but low discontinuation rates and no clinically meaningful increase in immune-related adverse events were observed,” Paz-Ares said. The safety profile was predictable, he noted.

Grade 5 TRAEs occurred in 0.8% (n = 2; sepsis, febrile neutropenia) and 0.4% (n = 1; sepsis) of patients, respectively. Treatment was discontinued due to AEs in 6.2% of the combination group and 3.3% of the atezolizumab-alone group.

“IMforte is the first phase 3 trial to show meaningful improvement in PFS and OS with first-line maintenance treatment in extensive-stage small cell lung cancer,” Paz-Ares said. “It highlighted the potential of lurbinectedin plus atezolizumab to become a new standard of care in this patient population as maintenance treatment, particularly considering this aggressive and difficult-to-treat disease.”

Based on these findings, lurbinectedin plus atezolizumab, which is currently FDA approved in the second-line maintenance setting, may be moved into the first-line maintenance setting, moderator Julie R. Gralow, MD, FACP, FASCO, chief medical officer (CMO) of ASCO, noted. She added that, despite the positive PFS and OS outcomes in the IMforte trial, there is a need for more research to further improve outcomes in ES-SCLC.

"The study is important because both progression-free and overall survival were increased," Gralow said. "But I would point out, while this is a next step, progression-free survival is still quite low in both arms, and we need to work on additional ways of advancing this even further. It is a small next step. It is extending the time that the tumor doesn't progress and the amount of time that the patients are living, but we need to do more research in extensive-stage small cell lung cancer, as well."

Reference

1. Paz-Ares LG, 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. Presented at: 2025 American Society of Clinical Oncology Annual Meeting; May 31-June 5, 2025; Chicago, IL. Abstract 8006

2. A phase III, open-label study of maintenance lurbinectedin in combination with atezolizumab compared with atezolizumab in participants with extensive-stage small-cell lung cancer (IMforte). ClinicalTrials.gov. Updated April 24, 2025. Accessed May 22, 2025. https://clinicaltrials.gov/study/NCT05091567