Dr Liu on Lurbinectedin: A New Era in SCLC Maintenance
New research reveals that combining lurbinectedin with atezolizumab significantly improves survival rates for patients with extensive-stage small cell lung cancer.
Small cell lung cancer (SCLC) remains an aggressive and challenging malignancy, often presenting at an advanced stage with rapid progression and limited long-term survival. Despite initial responsiveness to chemotherapy and recent advancements with immunotherapy, a significant unmet need persists in preventing disease relapse and extending survival for these patients.
At the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting, results from the phase 3 IMforte study (NCT05091567) were unveiled, offering a new beacon of hope.This pivotal trial investigated the efficacy of maintenance lurbinectedin (Zepzelca) in combination with atezolizumab (Tecentriq) following induction chemoimmunotherapy for patients with extensive-stage SCLC.
In an interview with Targeted OncologyTM, Stephen Liu, MD, associate professor of medicine, director of Thoracic Oncology, and director of Developmental Therapeutics at the Lombardi Comprehensive Cancer Center of Georgetown University, delved into the implications of these findings. Liu discussed the rationale behind the IMforte study, its methodology, and the transformative findings that could redefine the standard of care for patients battling this formidable disease.
Targeted OncologyTM: What was the rationale for this study presented at ASCO. What were the unmet needs that prompted the research?
Stephen Liu, MD
Liu: The IMforte trial is a phase 3 study investigating maintenance lurbinectedin after induction chemoimmunotherapy for patients with small cell lung cancer. Small cell lung cancer is an extremely aggressive disease, typically presenting at an advanced stage. While chemotherapy initially works well, responses are often transient. The addition of immunotherapy to chemotherapy has extended survival for a subset of patients, but most still experience relapse.
A significant challenge with small cell lung cancer is the high rate of attrition at relapse; many patients, sometimes over half, do not receive further therapy. This is because the cancer often returns very aggressively, leaving patients unfit or unwell for additional treatment. Therefore, there's a critical need to prevent progression and maintain disease control proactively, rather than waiting for relapse. This trial aimed to address this by exploring a maintenance strategy using lurbinectedin. While maintenance strategies are logical, there hadn't been a positive study showing improved survival with such an approach until this trial.
Could you summarize the methodology for this trial?
This was a randomized phase 3 trial for patients with extensive-stage small cell lung cancer. Patients could not have received prior therapy for extensive-stage disease, and those with brain metastases were excluded. All participants received standard induction therapy, consisting of 4 cycles of carboplatin, etoposide, and atezolizumab. After induction, patients with no evidence of progression and an ECOG performance status of 0 to 1 were randomized to either continue atezolizumab maintenance alone, which is standard practice, or to add lurbinectedin to atezolizumab.
Lurbinectedin was administered at a dose of 3.2 mg/m2 every 3 weeks, with primary prophylaxis using [granulocyte colony-stimulating factor (G-CSF)] to prevent prolonged neutropenia and reduce the risk of myelosuppression. The primary end points were investigator-assessed progression-free survival [PFS] and overall survival [OS].
What were the findings? What do you consider to be the implications of these findings?
The IMforte trial met both of its primary end points. We observed a significant improvement in progression-free survival, with the median PFS increasing from 2.1 months to 5.4 months. These median values are calculated from the time of randomization at maintenance and do not include the 3.2 months of induction therapy. The hazard ratio for PFS was 0.54. At the 6-month landmark point, 18.7% of patients in the standard treatment arm were progression-free, compared [with] 41.2% with the addition of lurbinectedin.
As expected with the addition of an active drug, there was an increase in toxicity. Treatment-related grade 3 to 4 adverse events occurred in 25.6% of patients in the combination arm vs 5.8% in the atezolizumab-alone arm. However, the rate of treatment discontinuation due to adverse events was surprisingly low: 6.2% with lurbinectedin and atezolizumab vs 3.3% with atezolizumab alone.
Crucially, the study also demonstrated an improvement in overall survival. Median OS increased from 10.6 months with standard treatment to 13.2 months with the combination of lurbinectedin and atezolizumab. This 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.
What questions do you still have, and what research still needs to be done?
While the IMforte trial unequivocally shows that adding lurbinectedin to maintenance improves survival, which is a landmark achievement, several questions remain. For instance, we need to understand better who specifically derives the most benefit from this treatment. Further research is also needed to identify mechanisms of resistance and how we can further improve patient outcomes. Patients with brain metastases were excluded from this study, so it remains to be seen if patients with treated brain metastases would experience similar benefits. Other studies or real-world evidence could help fill these knowledge gaps.
Ultimately, our goal is to achieve better outcomes and longer survival for our patients. The addition of immunotherapy to chemotherapy was a major advance, and now, with the first positive maintenance approach, we can offer patients a more prolonged benefit. Furthermore, ongoing studies are improving second-line treatment options for patients who do recur and require subsequent therapy. We are finally starting to see much-needed progress in this highly lethal disease.
