Lurbinectedin and Atezolizumab Combo Improves Survival in Extensive-Stage Small-Cell Lung Cancer

A phase 3 trial published in The Lancet found that combining Zepzelca (lurbinectedin) with Tecentriq (atezolizumab) as first-line maintenance therapy for extensive-stage small-cell lung cancer (ES-SCLC) significantly improved survival outcomes compared to atezolizumab alone—though with a higher rate of side effects.

Small-cell lung cancer (SCLC) is a fast-growing and aggressive form of lung cancer, accounting for about 15% of all lung cancer cases.

It’s characterized by small, round cells that multiply quickly and often spread beyond the lungs before diagnosis.

When the disease has spread to distant parts of the body, it’s classified as extensive-stage, which applies to nearly two-thirds of SCLC cases at the time of diagnosis.

Standard first-line treatment for ES-SCLC typically includes chemotherapy—such as Paraplatin (carboplatin) and etoposide, which is sold under the names Etopophos, Toposar and Vepesid—combined with immunotherapy.

Atezolizumab, a monoclonal antibody that targets the PD-L1 protein, is commonly used in this setting. By blocking PD-L1, atezolizumab helps reactivate the immune system’s T cells to attack cancer cells.

Lurbinectedin, approved for patients with relapsed SCLC, works by inhibiting transcription in cancer cells, interfering with their ability to grow and divide.

Atezolizumab is approved for some of the most aggressive and difficult-to-treat forms of cancer. It was the first cancer immunotherapy approved for the treatment of a certain type of early-stage (adjuvant) non-small cell lung cancer (NSCLC), SCLC and hepatocellular carcinoma (HCC), according to Roche.

It is also approved in countries around the world, either alone or in combination with targeted therapies and/or chemotherapies, for various forms of metastatic NSCLC, certain types of metastatic urothelial cancer (mUC), PD-L1-positive metastatic triple-negative breast cancer (TNBC), BRAF V600 mutation-positive advanced melanoma and alveolar soft part sarcoma (ASPS).

In addition to intravenous infusion, atezolizumab has been approved as a subcutaneous injection.

The IMforte trial investigated whether combining atezolizumab with lurbinectedin could improve outcomes when used as maintenance therapy in patients whose cancer had not progressed after induction treatment.

The randomized, open-label, phase 3 study was conducted across 96 hospitals in 13 countries.

It enrolled adults with newly diagnosed ES-SCLC who received four 21-day cycles of induction therapy with atezolizumab, carboplatin and etoposide.

Patients whose disease remained stable after induction were randomly assigned to maintenance treatment every three weeks with either atezolizumab alone or in combination with lurbinectedin (3.2 mg/m²), along with prophylactic granulocyte colony-stimulating factor to help reduce the risk of infection.

A total of 483 patients entered the maintenance phase, with 242 receiving the combination therapy and 241 receiving atezolizumab alone.

Patients in the combination group showed significantly improved outcomes: median progression-free survival was 5.4 months compared to 2.1 months for atezolizumab alone, representing a 46% reduction in the risk of disease progression or death.

Median overall survival was 13.2 months in the combination group compared to 10.6 months in the atezolizumab-only group, a 27% reduction in the risk of death.

However, these benefits came with an increased rate of adverse events.

Grade 3–4 side effects occurred in 38% of patients in the combination group versus 22% in the atezolizumab-only group.

The most common severe side effects among combination therapy patients were anemia, decreased neutrophil count and decreased platelet count.

Grade 5 events occurred in 5% of the combination group and 3% of the monotherapy group.

Myelosuppressive toxicities, such as neutropenia and leukopenia, were also more frequent in the combination arm—highlighting a trade-off between improved survival and increased toxicity.

No new safety signals were observed.

Lead study author Luis Paz-Ares, M.D., Ph.D., chair of medical oncology at Hospital Universitario 12 de Octubre in Madrid, expressed the promise of the combination therapy during a press briefing at ASCO 2025, as reported by The ASCO Post.

“This study supports the potential for this combination to become a new standard of care for this aggressive disease,” he said.

Paz-Ares also stated in a press release from Roche:

“The IMforte results are very encouraging showing a potentially practice-changing option that could improve survival for patients with a very high unmet need,” he said.

Levi Garraway, M.D., Ph.D., Roche’s chief medical officer and head of global product development, added that in the study, the combination drug maintenance regimen “significantly extended survival for people” living with ES-SCLC.

“This study builds on Tecentriq’s well-established safety and efficacy profile as the first immunotherapy for this cancer type and may provide another approach to help physicians and patients better manage this aggressive disease,” Garraway said.