Maintenance Therapy Combo Bolsters Survival in Extensive-Stage SCLC

Photo Credit: iStock.com/OGphoto

Findings suggest that adding lurbinectedin to atezolizumab for first-line maintenance therapy benefits patients with extensive-stage small cell lung cancer.

Adding lurbinectedin to atezolizumab for maintenance therapy in the first-line setting improved survival outcomes among patients with extensive-stage small cell lung cancer (ES-SCLC), according to findings presented at the 2025 ASCO Annual Meeting.

Luis Paz-Ares, MD, PhD, and colleagues wrote that adding first-line PD-L1 inhibitors to platinum-based chemotherapy has been shown to improve treatment efficacy in this patient population, but long-term survival data are lacking.

The researchers reported preliminary results from the phase 3 IMforte study, a randomized trial testing lurbinectedin plus atezolizumab versus atezolizumab alone as first-line maintenance therapy in patients with ES-SCLC.

Inside the IMforte Study

The study enrolled 660 treatment-naïve patients. Patients received standard induction with atezolizumab, carboplatin, and etoposide for four 21-day cycles (q3w).

From there, the investigators randomly assigned eligible patients who did not experience disease progression to maintenance treatment q3w with 3.2 mg/m2 lurbinectedin with G-CSF prophylaxis plus 1,200 mg atezolizumab, or atezolizumab alone. Participants underwent treatment until progression, unacceptable toxicity, or withdrawal.

The researchers stratified patients by the presence of liver metastases at induction baseline, prophylactic cranial irradiation prior to treatment randomization, ECOG performance score, and lactate dehydrogenase level at maintenance baseline. The arms had comparable baseline characteristics, and the primary endpoints of the study were independent review facility-assessed progression-free survival (PFS) and overall survival (OS), measured from the date of randomization into maintenance therapy.

Combination Shows Survival Benefit

A total of 242 patients received lurbinectedin plus atezolizumab, and 241 received atezolizumab alone. With a median of 15 months of follow-up, the combination arm demonstrated significant advantages in PFS (stratified HR, 0.54; 95% CI, 0.43-0.67; P<0.001) and OS (stratified HR, 0.73; 95% CI, 0.57-0.95; P=0.0174).

The median duration of maintenance treatment was 4.1 months with lurbinectedin and 4.2 months with atezolizumab in the combination arm, compared with 2.1 months among patients receiving only atezolizumab.

Regarding safety, treatment-related adverse events occurred in 83.5% in the combination arm compared with 40.0% in the atezolizumab arm, with a greater proportion of patients experiencing grade 3 or 4 adverse events in the combination arm (25.6%) than the atezolizumab arm (5.8%).

Two patients receiving lurbinectedin plus atezolizumab had grade 5 adverse events, including sepsis and febrile neutropenia; one patient in the atezolizumab arm had sepsis. The researchers reported that 6.2% of patients in the combination arm discontinued treatment due to adverse events, compared with 3.3% in the atezolizumab arm.

The study authors concluded that the trial met its primary endpoints, with lurbinectedin plus atezolizumab demonstrating a clinically meaningful survival benefit over atezolizumab alone, with no new or unexpected safety signals.

“IMforte is the first global Phase 3 study to show PFS and OS improvement with first-line maintenance therapy for ES-SCLC and supports maintenance lurbinectedin + atezolizumab as a new option for patients with this aggressive disease,” Dr. Paz-Ares and colleagues wrote.

The study was funded by Genentech.