IMforte Trial: A Potential First-Line Maintenance Therapy for Extensive-Stage Small Cell Lung Cancer

Sawyer Bawek, DO University at Buffalo

With the American Society of Clinical Oncology (ASCO) Annual Meeting just around the corner, abstracts were officially released on May 22, sparking buzz across the oncology community. Many potentially practice-changing abstracts are being presented, with some being released during the highly anticipated annual meeting (stay tuned for updates).  

One particular abstract has the potential to reshape first-line maintenance therapy in extensive-stage small cell lung cancer (ES-SCLC). IMforte (NCT05091567) evaluated lurbinectedin and atezolizumab in this role in patients with ES-SCLC. Let’s dive into the abstract highlights of this global, open-label, randomized phase 3 trial.

Key Takeaways from the IMforte Trial

Progression-Free Survival

• Patients receiving lurbinectedin and atezolizumab as first-line maintenance had a median progression-free survival (PFS) of 5.4 months compared with 2.1 months for those getting atezolizumab alone (HR, 0.54; P <.0001).

Overall Survival 

• Median overall survival (OS) was 13.2 months for patients treated with lurbinectedin and atezolizumab versus 10.6 months for those receiving atezolizumab alone (HR, 0.73, P = .0174).

Treatment-Related Adverse Events

• Lurbinectedin plus atezolizumab: 83%
• Atezolizumab alone: 40%

Median Maintenance Therapy

• Lurbinectedin plus atezolizumab: 4.1 months (lurbinectedin), 4.2 months (atezolizumab)
• Atezolizumab alone: 2.1 months

Grade 3-5 Adverse Events

• Grade 3-4, lurbinectedin and atezolizumab: 25%
• Grade 3-4, atezolizumab alone: 5.8%
• Grade 5, lurbinectedin and atezolizumab: 0.8%
• Grade 5, atezolizumab alone: 0.4%

Treatment Discontinuation Due to Adverse Events

• Lurbinectedin and atezolizumab: 6.2%
• Atezolizumab alone: 3.3%

Extensive-Stage Small-Cell Lung Cancer Overview 

SCLC represents 10% to 15% of all lung cancers, and more than two-thirds of patients receive a diagnosis of ES-SCLC. The landmark IMpower133 trial, published in 2018 in The New England Journal of Medicine, introduced immunotherapy to frontline therapy. The findings showed sustained OS benefit from adding immunotherapy targeting the PD-L1/PD-1 pathway to platinum-based chemotherapy. The study analyzed the addition of atezolizumab combined with chemotherapy and found, compared with placebo, improved OS (12.3 months vs, 10.3 months; P = .0007) and improved median PFS (5.2 months vs. 4.2 months; P = .02). The safety profile was consistent with previous reports.

Although adding immunotherapy to first-line therapy has shown improved outcomes, ES-SCLC remains challenging to treat because of therapeutic resistance. The median survival time for ES-SCLC is approximately 1 year. There remains an unmet need for prolonged disease control beyond current established therapies. 

IMforte Trial Design

• Population: Treatment-naive patients with ES-SCLC received standard induction treatment with atezolizumab, carboplatin, and etoposide in 21-day cycles. 
• Study arms: Patients without disease progression were randomized 1:1 to receive maintenance therapy of either lurbinectedin plus atezolizumab or atezolizumab alone.

Takeaway for Community Oncologists

The IMforte trial demonstrated that, compared with atezolizumab alone, adding lurbinectedin to atezolizumab improved both PFS and OS in patients with ES-SCLC. However, the combination therapy did show increased toxicity, which should be considered when discussing treatment goals with patients.

The findings from the IMforte trial will be formally presented at ASCO 2025 along with other potentially practice-changing data.