A New Wave Of Treatments Is Providing Hope For Small Cell Lung Cancer Patients

“Rapid progression, poor outcomes … typically it’s diagnosed in late stages, something we call extensive stage in the case of small cell lung cancer, and the traditional treatment for that extensive stage have been mostly conventional combination chemotherapy,” he adds.

When the cancer has spread throughout the lung or to other parts of the body, it is classified as extensive-stage small cell lung cancer (ES-SCLC). This diagnosis can feel overwhelming, confusing, and stressful.

For people facing ES-SCLC, treatment has long relied on the same foundation: a conventional combination of chemotherapy — but patients often progress and second-line treatments had historically been largely ineffective, Dr. Halmos says.

However, new research is providing a wave of hope. A combination of anticancer drug lurbinectedin (brand name Zepzelca) and atezolizumab, a monoclonal antibody, is showing encouraging results, and an innovative immunotherapy called tarlatamab (brand name Imdelltra) is extending survival for those whose disease returns after chemotherapy.

Together, these developments mark real progress in a disease that for decades has been defined by relapse.

The Path Forward: Zepzelca

Zepzelca (lurbinectedin) is a prescription medicine used to treat adults with SCLC that has spread (metastatic) and has progressed after receiving platinum-based (regular) chemotherapy.

Clinical results, including real-world evidence, support its role in this setting. In one retrospective, multi-center study involving 59 patients who had already received treatment, Zepzelca showed an overall response rate (ORR) of 37.3%, meaning tumors shrank or disappeared.

Beyond its role as a second-line treatment, Zepzelca is now making waves in the initial phase of treatment — as a maintenance therapy.

The current standard of care for first-line ES-SCLC includes regular chemotherapy combined with immunotherapy (like atezolizumab or durvalumab). However, the IMforte phase 3 trial investigated whether adding Zepzelca to atezolizumab as maintenance therapy could extend the benefit for patients whose cancer had not progressed after the initial chemo-immunotherapy course.

Results Spark Hope

This was a large study of 895 patients with extensive-stage SCLC who had completed initial chemotherapy and atezolizumab without disease progression. Patients then received either atezolizumab alone or atezolizumab plus Zepzelca as maintenance therapy.

The addition of Zepzelca maintenance to atezolizumab maintenance improved both median progression-free survival, which is how long people live without the cancer getting worse (5.4 months versus 2.1 months), and overall survival, which is the amount of time a person stays alive after diagnosis or treatment begins (13.2 months versus 10.6 months).

“It’s always difficult to look at these average numbers and get very excited: 10 months versus 12 months. Is that significant? Well, we do view them as significant,” Dr. Halmos explains.

“They come at some cost in terms of added time on treatment, some cost of added adverse events. But at the same time, when we talk about averages, nobody’s average, every patient is different. And it’s really those patients at the tail of the curve who don’t just get the two months,” he adds.

This combination (Zepzelca + atezolizumab) is now approved as maintenance treatment for adults with ES-SCLC who have not progressed after initial treatment with atezolizumab and carboplatin/etoposide chemotherapy.

The goal of maintenance therapy is crucial: to continue treating SCLC aggressively and help delay the time to progression or recurrence of the cancer.

Tarlatamab (Imdelltra): A Targeted Immunotherapy

For many, the most exciting breakthrough in treating relapsed ES-SCLC is tarlatamab-dlle (Imdelltra). This medication offers a different and highly effective approach, using sophisticated immunotherapy.

“A few years ago, we saw the introduction of what’s called immunotherapy into the treatment paradigm,” Dr. Halmos explains. “Those types of medicines had made a big change in small cell lung cancer management as well. Immunotherapy with chemotherapy now does a better job putting the cancer in remission and keeping it remission at least for some time.”

Imdelltra (tarlatamab) is a bispecific T-cell engager immunotherapy. It essentially links the body’s powerful immune cells directly to the cancer cells. It targets delta-like ligand 3 (DLL3), a protein that is often highly expressed on the surface of SCLC cancer cells (found in 85% to 96% of patients), but is largely absent in normal tissues. By binding to DLL3 on the cancer cell and to CD3 on the T-cells, Imdelltra creates a connection that triggers the T-cells to attack and destroy the tumor cell.

Landmark Approval and Efficacy

In May 2024, the Food and Drug Administration (FDA) granted accelerated approval to Imdelltra for adults with extensive-stage SCLC whose disease progressed on or after regular chemotherapy.

This approval was based on compelling results from the DeLLphi-304 phase 3 clinical trial, which compared Imdelltra to standard chemotherapy in patients whose SCLC who had progressed after platinum-based treatment.

The results showed a significant benefit in overall survival for the patients receiving Imdelltra compared to chemotherapy — 13.6 months versus 8.3 months for chemotherapy.

Imdelltra also showed benefit in progression free survival, with a median of 4.2 months compared to 3.7 months for chemotherapy. The objective response rate was 35% in the Imdelltra group, compared with 20% in the chemotherapy group.

Furthermore, treatment with Imdelltra led to better patient-reported outcomes, resulting in significant decreases in symptoms like dyspnea (shortness of breath) and cough compared with chemotherapy. The incidence of serious side effects was also lower with Imdelltra (54%) than with chemotherapy (80%)

“There’s more and more reason to invest the immune treatment for that long-term benefit,” says Dr. Halmos.

“The hope, the light at the end of the tunnel that for some patients now we can make the transformational change. A deadly disease suddenly is not just a disease that we can control, but … sometimes we can put it into a long-term remission and if we can do it for some patients, that raises the hope,” Dr. Halmos adds.

“Maybe in the future we could do it for more patients if we push the science forward, if we understand better how to use our treatments.”

Questions To Ask Your Doctor

• Am I eligible for maintenance therapy with Zepzelca (lurbinectedin) plus atezolizumab?
• If my cancer comes back, would tarlatamab (Imdelltra) be an option for me?
• What are the most common side effects of these treatments?
• Are there clinical trials nearby that I should consider?
• What can I do to maintain my strength and quality of life during treatment?

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