FDA Approval of Lurbinectedin/Atezolizumab As First-Line Maintenance Expands Limited Post-Induction Arsenal for ES-SCLC

November 18, 2025

Joshua K. Sabari, MD, discusses the FDA approval of lurbinectedin plus atezolizumab as first-line maintenance therapy in extensive-stage SCLC.

Lurbinectedin (Zepzelca) plus atezolizumab (Tecentriq) with or without hyaluronidase-tqjs (Tecentriq Hybreza) is the first approved maintenance regimen beyond immunotherapy alone to improve both progression-free survival (PFS) and overall survival (OS) for patients with extensive-stage small cell lung cancer (ES-SCLC) whose disease has not progressed after frontline induction therapy; however, the effect of introducing an additional cytotoxic agent at a juncture when patients might otherwise receive a break from chemotherapy should be carefully weighed during treatment selection, according to Joshua K. Sabari, MD.1,2

The October 2025 FDA approval of lurbinectedin (Zepzelca) plus atezolizumab was supported by data from the phase 3 IMforte trial (NCT05091567), in which lurbinectedin plus atezolizumab (n = 242) produced a median PFS by independent review facility of 5.4 months (95% CI, 4.2-5.8) vs 2.1 months (95% CI, 1.6-2.7) with atezolizumab alone (n = 241; stratified HR, 0.54; 95% CI, 0.43-0.67; 2-sided P < .0001).1,2

“[IMforte] allowed us to see a 3-month improvement in OS in patients receiving lurbinectedin plus atezolizumab vs atezolizumab alone,” Sabari, an assistant professor in the Department of Medicine at NYU Grossman School of Medicine, as well as the director of High Reliability Organization Initiatives at the Perlmutter Cancer Center in New York, New York, said in an interview with OncLive®. “This [approach] is practice-changing and has been readily adopted in clinical practice.”

In the interview, Sabari outlined the clinical significance of this FDA approval, reviewed key design elements and findings from the IMforte trial, and emphasized the practice-changing nature of results from this trial for the ES-SCLC treatment paradigm.

Why Is The Approval of First-Line Maintenance Lurbinectedin/Atezolizumab So Significant?

The FDA approved lurbinectedin plus atezolizumab or atezolizumab and hyaluronidase-tqjs as maintenance therapy for adult patients with ES-SCLC whose disease has not progressed after first-line induction therapy with atezolizumab-based chemotherapy.
This regulatory decision was supported by results from the phase 3 IMforte trial, which demonstrated significant PFS (HR, 0.54; 95% CI, 0.43-0.67; P < .0001) and OS benefit (HR, 0.73; 95% CI, 0.57-0.95; P = .0174) with lurbinectedin plus atezolizumab vs atezolizumab alone.
The combination offers a new standard of care in the first-line maintenance setting for eligible patients with good performance status and adequate hematologic function, expanding a historically limited therapeutic arsenal.

OncLive: What is the significance of the FDA approval of lurbinectedin plus atezolizumab in the frontline maintenance setting for ES-SCLC?

Sabari: SCLC is an uncommon disease. There are about 30,000 cases per year in the United States. It is an aggressive disease. The standard of care in the frontline setting is still carboplatin, etoposide, and a PD-L1 inhibitor, either atezolizumab or durvalumab [Imfinzi]. The median OS for patients with extensive-stage SCLC remains dismal; it is approximately 12 months.

We have novel therapies approved in the second-line setting. For example, [there is] tarlatamab [Imdelltra], a CD3/DLL3 bispecific T-cell engager. We also have lurbinectedin, a novel chemotherapeutic with an accelerated approval in the second-line setting.

[Before this approval], we did not have any approved agents in the maintenance setting. Historically, after a patient finishes 4 cycles of carboplatin and etoposide in the frontline with or without that PD-L1 inhibitor, we would continue [to administer] a PD-L1 inhibitor in the maintenance setting. [However,] the median time on that PD-L1 inhibitor is probably 3 to 4 months before progression of disease.

What was the design of the IMforte study?

IMforte evaluated maintenance atezolizumab plus lurbenectinen vs atezolizumab alone. It's an interestingly designed trial because patients were enrolled upfront, so patients received 4 cycles of carboplatin, etoposide and atezolizumab. Then, if they achieved a response or disease stability, they were then randomly assigned to receive lurbinectedin plus atezolizumab vs atezolizumab alone.

It is important to note that there was a population of patients who did not go on to the randomization period; those are patients who had primary progressive disease. Outcomes for patients who have primary progressive disease are quite poor. However, over 70% to 80% of our patients had a response in the clinic.

What key efficacy outcomes were reported from this trial?

We saw impressive improvements in both event-free survival or PFS, as well as OS, in this patient population. Moreover, there was a near doubling of survival in patients who received lurbinectedin plus atezolizumab vs atezolizumab alone. This is a practice-changing study in the maintenance setting for patients with extensive-stage SCLC.

What was the safety profile of this regimen?

Lurbinectedin is a chemotherapeutic. We have a lot of experience using chemotherapies in oncology. It is important to monitor patients’ counts, specifically their blood counts, particularly after coming off 4 cycles of carboplatin and etoposide. [The adverse effects] to look out for are neutropenia and thrombocytopenia, but these are well managed in clinical practice.

The caveat of using lurbinectedin in the maintenance setting is that patients are just recovering from their chemotherapy. We do see slightly higher rates of toxicity, particularly hematologic toxicity. Therefore, it is important to select patients who are fit, who have a good performance status, and whose hematologic parameters meet the requirements for the utilization of lurbinectedin and atezolizumab. [Keeping this in mind, lurbinectedin plus atezolizumab] is something I will be using in this setting in my own clinical practice.

Overall, why is this approval significant?

[The IMfore trial] is truly a practice-changing study. There are many other ongoing maintenance trials [in SCLC] right now. [With this approval], however, patients who are not eligible for maintenance trials should be offered lurbinectedin plus atezolizumab in the maintenance setting for ES-SCLC.

References

FDA approves lurbinectedin in combination with atezolizumab or atezolizumab and hyaluronidase-tqjs for extensive-stage small cell lung cancer. FDA. October 2, 2025. Accessed November 17, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lurbinectedin-combination-atezolizumab-or-atezolizumab-and-hyaluronidase-tqjs-extensive?utm_medium=email&utm_source=govdelivery
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