Dr Sabari on the FDA Approval of Maintenance Lurbinectedin Plus Atezolizumab for ES-SCLC

“It’s important to select patients who are fit, who have a good performance status, and whose hematologic parameters meet the utilization of lurbinectedin and atezolizumab. However, I will be using [this combination] in my clinical practice."

Joshua K. Sabari, MD, 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, discussed the significance of the FDA approval of lurbinectedin (Zepzelca) plus atezolizumab (Tecentriq) as first-line maintenance therapy for patients with extensive-stage small cell lung cancer (ES-SCLC).

On October 2, 2025, the FDA approved lurbinectedin plus atezolizumab or atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza) for the first-line maintenance treatment of adult patients with ES-SCLC whose disease has not progressed after frontline induction treatment with atezolizumab or atezolizumab plus hyaluronidase, carboplatin, and etoposide. This regulatory decision was supported by data from the phase 3 IMforte trial (NCT05091567). In IMforte, patients who received lurbinectedin plus atezolizumab (n = 242) achieved a median progression-free survival 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 monotherapy (n = 241; stratified HR, 0.54; 95% CI, 0.43-0.67; 2-sided P < .0001).

SCLC is classified as a relatively uncommon malignancy, accounting for approximately 30,000 new cases annually within the United States, Sabari began. This disease is inherently characterized by its aggressive biological behavior, he said. The contemporary frontline standard of care for patients presenting with ES-SCLC involves a cytotoxic regimen comprising carboplatin and etoposide, administered in conjunction with an immune checkpoint inhibitor targeting the PD-L1 axis, specifically either atezolizumab or durvalumab (Imfinzi), he noted. Despite these therapeutic interventions, the median overall survival (OS) for patients with ES-SCLC is only approximately 12 months, he explained.

Recent therapeutic advancements include the introduction of novel agents approved in the second-line SCLC setting, such as tarlatamab-dlle (Imdelltra), which functions as a CD3/DLL3 bispecific T cell engager, and lurbinectedin, a distinct chemotherapeutic agent, according to Sabari. Historically, there have been no established agents approved for use in the first-line maintenance setting, he continued. The maintenance phase is defined as the period following the completion of 4 induction cycles of carboplatin and etoposide, with or without the PD-L1 inhibitor, he stated. Conventionally, maintenance involved the continuation of the PD-L1 inhibitor, though the median duration until disease progression on this monotherapy typically spans only 3 to 4 cycles, he reported.

The investigation assessing the combination of lurbinectedin plus atezolizumab vs atezolizumab monotherapy in the maintenance setting represents a pivotal, practice-changing study, Sabari emphasized. The results demonstrated an improvement in OS for patients receiving the lurbinectedin combination regimen compared with atezolizumab monotherapy. This statistically significant benefit supports the adoption of this approach into routine clinical practice, he highlighted.

However, the integration of lurbinectedin into the maintenance phase carries a crucial caveat related to toxicity profiles, Sabari added. Given that patients are in immediate recovery from the intensive carboplatin/etoposide induction chemotherapy, investigators have observed slightly higher rates of toxicity with maintenance lurbinectedin plus atezolizumab, particularly hematologic adverse effects, including neutropenia and thrombocytopenia, he said. Therefore, optimal patient selection is essential, such as those who have a favorable performance status and whose hematologic parameters are adequate for the safe administration of the lurbinectedin and atezolizumab regimen, he concluded.