IMforte: Maintenance With Lurbinectedin in Newly Diagnosed ES-SCLC
October 6, 2025
Key Points
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First-line maintenance therapy with lurbinectedin plus atezolizumab improved overall survival (OS) in untreated patients with extensive-stage small cell lung cancer (ES-SCLC).
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First-line lurbinectedin plus atezolizumab maintenance is now a standard-of-care strategy in National Comprehensive Cancer Network (NCCN) guidelines.
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Introducing lurbinectedin into the frontline setting increased toxicities, particularly hematologic, but the adverse event management strategies used in the second-line setting remained effective.
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The maintenance approach is likely to be an attractive option for most patients who remain fit and have recovered hematologic parameters after induction therapy.
Changes in the ES-SCLC Treatment Landscape
On the Oncology Brothers podcast, cohosts Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, were joined by three thoracic oncologists for a roundtable discussion on ES-SCLC treatment, with a focus on the recent approval of lurbinectedin plus atezolizumab as a first-line maintenance therapy based on the phase 3 IMforte trial.
Data from the trial were initially presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, an update was presented at the 2025 World Conference on Lung Cancer, and most recently, the maintenance regimen was added to the NCCN guidelines as a new standard-of-care strategy for untreated ES-SCLC.
IMforte Trial Design and Outcomes
Isabel Preeshagul, DO, MBS, of Memorial Sloan Kettering Cancer Center, provided an overview of the IMforte trial. The study enrolled untreated patients with newly diagnosed ES-SCLC. After induction with carboplatin, etoposide, and atezolizumab, patients who achieved stable disease or better were randomized to lurbinectedin plus atezolizumab or atezolizumab alone every 3 weeks for maintenance therapy. Maintenance was continued until disease progression or intolerability.
The IMforte analysis reported that median OS from time of randomization was 10.6 months with atezolizumab alone versus 13.2 months with lurbinectedin plus atezolizumab (stratified hazard ratio [HR], 0.73; 95% CI, 0.57–0.95; P = .017), and the 1-year OS rates were 44% and 56%, respectively. The progression-free survival (PFS) from time of randomization was 2.1 months with atezolizumab alone versus 5.4 months (stratified HR, 0.54; 95% CI, 0.43–0.67; P < .0001) with the combination.
Adverse Events With Lurbinectedin
In IMforte, the main adverse events associated with lurbinectedin included fatigue, nausea, and cytopenias. Rare events such as rhabdomyolysis were also reported. Notably, the study protocol incorporated granulocyte colony-stimulating factor (G-CSF) as primary prophylaxis against neutropenia, and most patients continued G-CSF when starting maintenance therapy. The panelists agreed that proactive G-CSF support should be considered standard practice when using lurbinectedin in the frontline setting.
The lurbinectedin group experienced more toxicities, including nausea, fatigue, anemia, and neutropenia, though most events were low grade, and only 6% of patients discontinued any component of treatment due to toxicity. Adverse events typically occurred within the first 9 weeks of therapy, and dose interruptions were mostly driven by hematologic toxicities, said Stephen Liu, MD, of Georgetown Lombardi Cancer Center, an author on the initial IMforte report. Despite the additional toxicities, the median duration of treatment in IMforte was longer in the combination arm versus the atezolizumab monotherapy arm.
Impact of IMforte for Clinicians
The IMforte maintenance regimen is the third approval in the frontline ES-SCLC space alongside carboplatin, etoposide, and atezolizumab based on the IMpower133 trial, and carboplatin, etoposide, and durvalumab based on the CASPIAN trial. While ES-SCLC remains difficult to treat, the IMforte data build upon earlier improvements in outcomes achieved with immunotherapy-based induction and maintenance approaches, noted Ticiana Leal, MD, of Winship Cancer Institute of Emory University.
The panelists discussed which patients may not be appropriate candidates for maintenance. In IMforte, to be eligible for maintenance randomization, patients had to have recovered hematologic parameters, no disease progression, and good performance status. “I think we will know [ineligible patients] when we see them, certainly if someone is progressing, we don’t talk about maintenance therapy, we talk about second-line treatment, it really would be a different strategy,” Dr. Liu said. If patients have prolonged cytopenias, this may not be the ideal strategy, he noted.
Is Lurbinectedin Effective For CNS Involvement?
Overall, lurbinectedin does not have substantial evidence for central nervous system (CNS) activity. The IMforte protocol allowed up to 9 weeks of prophylactic cranial irradiation between the end of induction and the start of maintenance. While CNS involvement is not a contraindication for lurbinectedin use, additional radiation therapy ideally should be pursued, suggested Dr. Liu. “Those patients, if anything, are at higher risk for relapse, and potentially are more likely to gain a benefit from a more aggressive maintenance strategy,” he said.
Key Takeaways
In closing, Dr. Liu addressed potential concerns regarding maintenance strategies and whether saving treatments for the second-line setting would be more effective. Crucially, less than half of patients with SCLC receive any second-line therapy.
“The point of this maintenance strategy is to be proactive to prevent progression and give our patients more time,” Dr. Liu said. “If we wait until progression, many patients won’t start any second line therapy despite approved options because the act of progression itself can be fatal or make patients too sick.”
Drs. Preeshagul and Leal both stressed the importance of shared and informed decision-making with individual patients, agreeing that the lurbinectedin maintenance strategy is an important and exciting advancement for patients with ES-SCLC, and will likely be an option discussed with the majority of eligible patients.