Breakthroughs in Small-Cell Lung Cancer (SCLC) Treatment

Researchers continue to examine new drugs and new combinations of drugs to treat small-cell lung cancer (SCLC). Learn about newly approved drugs, combination treatments, and future therapies currently under investigation.

Small-cell lung cancer (SCLC) makes up about 15% of lung cancers in the United States. SCLC tends to be aggressive and has often spread to distant body parts by the time it’s diagnosed.

Early stage SCLC is usually treated with some combination of:

The late stage disease is primarily treated with:

• chemotherapy
• radiation therapy
• immunotherapy

Researchers are continuing to investigate new treatment options for SCLC by:

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• studying new drugs
• examining whether drugs used for other cancers are also effective for SCLC
• studying new combinations of already approved drugs

In this article, we look at some of the most recently approved treatment options and some of the potential future treatment options that are currently under investigation in clinical trials. Visit the National Cancer Institute website for a full list of approved drugs for lung cancer .

What are clinical trials?

Clinical trials are studies that investigate new treatment options to see if they’re safe and effective. A treatment can become the new standard treatment if data from clinical trials show that it’s more effective than the current standard treatment and has an acceptable safety level.

Clinical trials are classified into phases depending on how far the research has advanced. Here’s the approximate goal of each phase:

• Phase 1: examine whether a treatment is safe
• Phase 2: examine whether a treatment is effective
• Phase 3: examine the strength of a treatment’s benefit compared with current treatments
• Phase 4: examine long-term side effects

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The Food and Drug Administration (FDA) granted accelerated approval to lurbinectedin (Zepzelca) on June 15, 2020 , for treating adults with metastatic SCLC with disease progression while on or after platinum-based chemotherapy. The FDA Accelerated Approval Program allows for early approval of certain drugs that currently fit an unmet need.

“Metastatic SCLC” means the cancer has spread to distant body parts. Platinum-based chemotherapy combined with the drug etoposide is the most widely used chemotherapy regimen for people with SCLC.

Lurbinectedin falls into a class of chemotherapy medications called “alkylating agents.” These drugs prevent cancer cells from replicating by damaging their DNA .

The most common side effects in a lurbinectedin phase 2 clinical trial were:

• fatigue — 12%
• pneumonia — 7%
• shortness of breath — 6%
• respiratory tract infections — 5%
• muscle pain — 4%

In the phase 2 clinical trial, 35% of people had a partial response to treatment after not responding to another chemotherapy regimen.

Durvalumab (Imfinzi) is a type of immunotherapy drug that stimulates your immune system to attack cancer cells.

The FDA approved durvalumab on March 27, 2020 , in combination with etoposide and either carboplatin or cisplatin, as a first-line treatment for people with extensive stage SCLC. Carboplatin and cisplatin are platinum-based chemotherapy drugs.

Extensive stage SCLC may have spread:

• throughout the lung
• to lymph nodes on the other side of your chest
• to other body parts such as your bone marrow

A “first-line treatment” means that it’s the first treatment for the cancer that doctors administer.

A phase 3 clinical trial found that half of the people who received durvalumab with chemotherapy lived at least 13 months compared with only 10.3 months for people who received chemotherapy alone.

The most common side effects were:

The drug trilaciclib (Cosela) was approved by the FDA on February 12, 2020 for decreasing chemotherapy-induced myelosuppression in adults with advanced SCLC when administered before platinum and etoposide chemotherapy or topotecan-containing chemotherapy.

“Myelosuppression” is when your bone marrow starts producing fewer blood cells, and it’s a common side effect of chemotherapy.

The most common side effects of trilaciclib are:

• fatigue
• low blood calcium
• low blood potassium
• low blood phosphate
• increase in the liver enzyme aspartate aminotransferase
• headache
• pneumonia

Three phase 2 clinical trials found that trilaciclib significantly reduced severe neutropenia, or the duration of severe neutrophilia, in the first cycle of chemotherapy compared with a placebo. “Neutropenia” is when you have low levels of white blood cells, called “neutrophils,” that help heal infection.

On March 18, 2019 , the FDA approved atezolizumab (Tecentriq) in combination with carboplatin and etoposide as a first-line treatment for adults with extensive stage SCLC. Atezolizumab is a type of immunotherapy called an “immune checkpoint inhibitor,” and it stimulates your immune system to attack cancer cells.

The approval was based on the results of a phase 3 clinical trial called “IMpower133.” In the trial, half of the people who received atezolizumab and chemotherapy lived at least 12.3 months, but half of the people who received a placebo with chemotherapy only lived 10.3 months.

The most common side effects of atezolizumab were:

• fatigue
• weakness
• nausea
• hair loss
• constipation
• decreased appetite

The FDA granted nivolumab (Opdivo) accelerated approval as a third-line treatment, on August 16, 2018 , for metastatic SCLC with progression after platinum-based chemotherapy and after at least one other type of therapy. Nivolumab is a type of immunotherapy called a “monoclonal antibody” that helps your immune system slow the growth of cancer cells.

The approval was based on the CheckMate-032 trial. In the trial, the overall response rate was 12% . In the 13 people who responded to treatment, the response lasted at least:

• 6 months in 77% of people
• 12 months in 62% of people
• 18 months in 39% of people

The most common side effects in the trial were:

The drug JBI-802 by Jubilant Therapeutics received FDA orphan drug designation for SCLC on January 5, 2023. “Orphan drug designation” means a drug company receives financial benefits for developing a drug for a rare disease.

A phase 1 and 2 clinical trial is currently recruiting participants to examine the maximum-tolerated dose of JBI-802 and the recommended dose for people with advanced solid tumors.

According to the most recent search results from clinicaltrials.gov, more than 30 phase 3 clinical trials examining SCLC treatments are currently active or recruiting. Here’s a summary of some of the goals of these studies:

• to compare combination HLX10/chemotherapy/radiation therapy with combination chemotherapy/radiation therapy in people with limited stage SCLC
• to investigate the benefit of durvalumab or durvalumab and tremelimumab as a treatment to kill any remaining cancer cells after successful chemoradiation therapy in people with limited stage SCLC
• to compare combination lurbinectedin/atezolizumab with atezolizumab alone as maintenance therapy in people with extensive stage SCLC after first-line therapy with carboplatin, etoposide, and atezolizumab
• to compare combination atezolizumab/carboplatin/etoposide plus tiragolumab with the combination plus a placebo in people with extensive stage SCLC who haven’t received previous chemotherapy
• to compare irinotecan liposome injection with topotecan in people with SCLC with disease progression after platinum-based first-line chemotherapy
• to compare two combination treatment regimens: treatment with combination pembrolizumab/vibostolimab plus combination etoposide/platinum chemotherapy followed by another round of combination pembrolizumab/vibostolimab and treatment with combination atezolizumab/etoposide/platinum chemotherapy that is followed by atezolizumab as a first-line treatment for extensive stage SCLC
• to compare the benefit of HLX10 plus carboplatin-etoposide chemotherapy with atezolizumab and chemotherapy in previously untreated extensive stage SCLC

SCLC tends to be aggressive and has usually spread to distant body parts by the time it has been diagnosed. Researchers are continuing to examine new drugs and combinations of drugs to treat SCLC.

If your condition is diagnosed as SCLC, a doctor may recommend participating in a clinical trial that may give you access to state-of-the-art treatment.

You can find clinical studies that are currently recruiting by visiting the U.S. National Library of Medicine’s database.

Last medically reviewed on March 30, 2023