Updated NCCN Guidelines Add Lurbinectedin Maintenance in ES-SCLC

Updated National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for small cell lung cancer (SCLC) have added new recommendations for lurbinectedin (Zepzelca), based on data from the phase 3 IMforte trial (NCT05091567).¹

The updated guidelines now have a primary treatment option for extensive-stage (ES) SCLC of carboplatin AUC 5 on day 1, etoposide 100 mg/m² on days 1, 2, and 3, and atezolizumab (Tecentriq) 1200 mg on day 1 every 21 days for 4 cycles followed by maintenance lurbinectedin 3.2 mg/m² and atezolizumab 1200 mg on day 1 every 21 days.

The guidelines also suggest that physicians should consider adding lurbinectedin to maintenance atezolizumab in patients who have achieved at least stable disease following 4 induction cycles of chemoimmunotherapy, have an ECOG performance status of 0 to 1, and have no history of brain metastases. Additionally, the guidelines note that this regimen is not for retreatment in subsequent-line therapy if lurbinectedin has been used previously.

Data from IMforte were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in May. Here, frontline maintenance therapy with lurbinectedin and atezolizumab demonstrated a median progression-free survival (PFS) of 5.4 months (95% CI, 4.2–5.8) vs 2.1 months (95% CI, 1.6–2.7) with atezolizumab monotherapy.² This translated to a 46% reduction in the risk of disease progression or death (HR, 0.54; 95% CI, 0.43–0.67; 2-sided P <.0001). The 6-month PFS rates in the doublet vs monotherapy arms were 41.2% and 18.7%, respectively, and the 12-month PFS rates were 20.5% and 12.0%, respectively.

IMforte also showed a clinically meaningful benefit to overall survival (OS) with a median of 13.2 months (95% CI, 11.9–16.4) with the doublet vs 10.6 months (95% CI, 9.5–12.2) with the monotherapy (HR, 0.73; 95% CI, 0.57–0.95; 2-sided P =.0174). The 12-month OS rates were 56.3% with the doublet vs 44.1% with the monotherapy.

“[The OS] also does not include the 3.2 months of induction therapy. The OS hazard ratio was 0.73, which, in my opinion, establishes this as a new standard of care for patients with small cell lung cancer,” said Stephen V. Liu, MD, director of Thoracic Oncology and director of Developmental Therapeutics at the Lombardi Comprehensive Cancer Center of Georgetown University and IMforte investigator, in an interview with Targeted Oncology.

In June, the FDA accepted the supplemental new drug application (sNDA) of lurbinectedin plus atezolizumab as first-line maintenance therapy in ES-SCLC, supported by the IMforte data. The Prescription Drug User Fee Act target action date for the sNDA is October 7, 2025.³

Lurbinectedin is an alkylating agent that works by binding to DNA, disrupting cell cycle progression and leading to cell death. It received accelerated FDA approval in June 2020 for patients with metastatic SCLC with disease progression on or after platinum-based chemotherapy. Atezolizumab is an immune checkpoint inhibitor targeting PD-L1, which is already a component of standard first-line induction therapy for ES-SCLC. The synergy observed in preclinical models and now in the IMforte trial, combining the cytotoxic effects of lurbinectedin with the immune-modulating effects of atezolizumab, provides a strong biological rationale for this combination.

FAQs

What is the new recommendation in the updated NCCN guidelines for ES-SCLC?

The National Comprehensive Cancer Network (NCCN) has incorporated a new primary treatment option for extensive-stage small cell lung cancer (ES-SCLC). The updated guidelines now recommend the addition of lurbinectedin (Zepzelca) to atezolizumab (Tecentriq) for maintenance therapy. This regimen follows the initial 4 cycles of standard chemoimmunotherapy, establishing a new therapeutic pathway for this patient population.

What clinical trial provided the evidence for this guideline change?

The evidence supporting this update comes from the pivotal phase 3 IMforte trial (NCT05091567). The primary objective of this study was to evaluate the efficacy of adding lurbinectedin to atezolizumab as a frontline maintenance therapy for patients with ES-SCLC, comparing this combination directly against maintenance with atezolizumab monotherapy.

How did the lurbinectedin combination impact progression-free survival (PFS)?

The addition of lurbinectedin to atezolizumab in the maintenance setting demonstrated a significant improvement in PFS compared with atezolizumab alone. This benefit translated to a substantial reduction in the risk of disease progression or death for patients receiving the combination therapy.

• Median PFS: The combination arm achieved a median PFS of 5.4 months (95% CI, 4.2–5.8), more than doubling the 2.1 months (95% CI, 1.6–2.7) observed in the monotherapy arm.
• Risk Reduction: This represented a 46% reduction in the risk of disease progression or death (Hazard Ratio [HR], 0.54; 95% CI, 0.43–0.67; P <.0001).
• PFS Rates:
  • 6-Month PFS: 41.2% for the combination vs. 18.7% for monotherapy.
  • 12-Month PFS: 20.5% for the combination vs. 12.0% for monotherapy.

What was the reported benefit to overall survival (OS)?

The IMforte trial also reported a clinically meaningful benefit in Overall Survival (OS) for patients receiving the lurbinectedin and atezolizumab combination.

• Median OS: The median OS for the combination arm was 13.2 months (95% CI, 11.9–16.4) compared with 10.6 months (95% CI, 9.5–12.2) for the monotherapy arm.
• Risk Reduction: The statistical analysis showed an HR of 0.73 (95% CI, 0.57–0.95; P =.0174) in favor of the combination therapy.
• 12-Month OS Rates: The 12-month OS rate was 56.3% in the combination arm, compared with 44.1% in the monotherapy arm.

REFERENCES:

1. Small Cell Lung Cancer Version 2.2026. NCCN Clinical Practice Guidelines in Oncology. September 16, 2026. Accessed September 22, 2025. https://tinyurl.com/4pap95m5

2. 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. Presented at: 2025 ASCO Annual Meeting; May 30-June 3, 2025; Chicago, IL. Abstract 8006.

3. Zepzelca® (lurbinectedin) and atezolizumab (Tecentriq®) combination granted U.S. FDA priority review for first-line maintenance treatment of extensive-stage small cell lung cancer. News release. Jazz Pharmaceuticals. June 10, 2025. Accessed September 22, 2025. https://tinyurl.com/4rmphj6y