Treatment

Small Cell Lung Cancer

Small cell lung cancer (SCLC) is a rare and aggressive form of lung cancer. Several factors make it challenging to treat with long-term success.

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Dr. Sands and Maida emphasize the critical role of innovative therapies and clinical trials in transforming small cell lung cancer care, encouraging patients to explore all available options for the best outcomes.

About

Small cell lung cancer (SCLC) is a rare and aggressive form of lung cancer. Several factors make it challenging to treat with long-term success.

  1. Screening is uncommon. The cancer is often in an advanced stage by the time it is diagnosed.
  2. The cancer is fast growing. Mutation in SCLC suppresses our body’s ability to hamper uncontrolled cell growth.
  3. SCLC is resistant to treatments and often comes back more aggressively after treatment. SCLC responds well to chemotherapy because of the cells’ rapid growth. The response rate is as high as 70%. However, the effects are short-lived. After treatment, the cancer recurs quickly and grows faster than before.
  4. There have been few advances in treatment or new treatments for small cell lung cancer.

Thankfully, the last factor has changed over the past few years due to scientists and doctors’ persistent research and other advances in the field. Now new treatments are available to offer hope to SCLC patients.

The Stages of Small Cell Lung Cancer

Doctors commonly divide SCLC into two stages, limited-stage and extensive-stage.

Limited-stage disease (LD) means the cancer is contained in one part of the chest. Although the tumor is in one place, surgery is rarely an option for limited-stage SCLC.

Extensive-stage disease (ED) means that the cancer has metastasized and spread to other parts of the body like the second lung, bone, or brain. Since SCLC, and lung cancer in general, is often not diagnosed until symptoms are present, most people (about 2 in 3) have extensive-stage SCLC when the cancer is found.

Types of Treatment

On May 16, 2024, the Food and Drug Administration granted accelerated approval to tarlatamab-dlle (Imdelltra, Amgen, Inc.) for extensive stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy.

This injectable medicine is an antibody that targets a protein on cancer cells called DLL3. By attaching to DLL3, tarlatamab helps the body’s immune system find and destroy the cancer cells. In a clinical trial, some patients who received tarlatamab had their tumors shrink or disappear for some time.

This application was granted priority review, breakthrough designation, and orphan drug designation.

Beginning in 2019, immunotherapy was added as part of the first-line treatment for extensive-stage small cell lung cancer. Immunotherapies can prolong the body’s response to conventional chemotherapy and offers a promising addition to SCLC treatment.

The immunotherapy drugs atezolizumab and durvalumab block the protein PD-L1 and boost the body’s immune response to cancer cells. When used in combination with chemotherapy, these drugs increased overall survival (OS) and progression-free survival (PFS) from chemotherapy alone.

(Recently, Merck pulled its immunotherapy drug pembrolizumab (Keytruda), a PD-1 inhibitor, for SCLC treatment. The drug failed to show statistically significant improvement in overall survival (OS) for SCLC patients. It is still an effective treatment for non-small cell lung cancer.)

Chemotherapy Support through Myelosuppression

In February of 2021, the FDA approved the drug trilaciclib (Coasela) for patients with extensive-stage SCLC undergoing chemotherapy. Trilaciclib limits the damage chemotherapy causes to bone marrow, called myelosuppression. This treatment makes patients less susceptible to fatigue and infection and less likely to need rescue interventions during treatment. They are more likely to finish their treatment on schedule.

Chemotherapy: Lubinectedin

Topotecan has been the standard chemotherapy drug for when SCLC comes back or spreads.

In 2020, the FDA approved the new chemotherapy drug lurbinectedin (Zepzelca) to treat metastatic SCLC that has progressed on or after platinum-based chemotherapy. Lubinectedin works by selectively blocking oncogenic transcription, or the process by which tumor cells reproduce. It interferes with the tumor cells’ reproduction cycle and causes cell death.

Lubinectedin’s approval was based on a phase 2 trial that evaluated the drug’s effectiveness in previously treated patients with advanced solid tumors. The study showed an overall response rate of 35 percent with a median duration response of 5.3 months.

The results of a recent phase 1b/2 trial presented at the World Conference on Lung Cancer in January 2021 showed a combination of lurbinectedin and irinotecan could be an effective second-line treatment for patients. Both patients with platinum-sensitive and nonsensitive disease exhibited improvements, as well as patients with brain metastases. The overall response rate (ORR) was 62 percent.

The safety and efficacy of lurbinectedin in combination with the immune checkpoint inhibitors nivolumab (Opdivo) and ipilimumab (Yervoy) is currently being investigated in a clinical trial among patients with relapsed or recurrent SCLC.

Tyrosine Kinase Inhibitor (TKI): Apatinib
Apatinib (Rivoceranib) is a tyrosine kinase inhibitor (TKI). TKIs decrease tumor growth by blocking tyrosine kinases enzymes, which are used for cell growth and division. Specifically, apatinib works by inhibiting vascular growth in tumor tissue while limiting damage to other cells.

Data from a phase 2 trial presented at the World Conference on Lung Cancer in 2021 showed improved outcomes for patients who have received prior treatment when apatinib is combined with a single-agent chemotherapy. The results showed promising efficacy and high tolerability for patients with advanced SCLC. Patients with limited-stage disease benefited as well, showing higher progression free survival rates (PSF).

This is good news, as the drug currently has Orphan Drug status in the US, with approval pending on the demonstration of efficacy and safety.

TKIs are a type of targeted therapy. Targeted therapies are treatments where the specific genetic makeup of a person’s lung cancer tumor (biomarker or oncogene) defines what treatment works for them. Previously these treatments had not been found helpful for SCLC patients. But with new drugs like apatinib and a new understanding of small cell lung cancer, these treatments could expand soon.

Personalized medicine involves treatments that are tailored to an individual’s body and specific cancer. In addition to targeted therapies like apatinib, research has furthered our understanding of small cell lung cancer and offered pathways to more effective and focused treatments for SCLC patients.

Small Cell Lung Cancer Subtypes

Although immunotherapy has become a standard of care, it has had limited success with SCLC. A study published in February 2021 may explain why; different drugs may be more or less effective for each subtype.

Researchers from The University of Texas MD Anderson Cancer Center categorized small cell lung cancer tumors into four major subtypes based on gene expression. Previous research had identified three possible subtypes but left a large number of tumors unclassified. The team pinpointed the fourth subtype by the inflamed gene signature with a high expression of multiple immune genes. They also identified potential therapeutic targets for each. The fourth group, for example, has a distinct biology that tends to be more responsive to immunotherapy.

Biomarkers

Biomarker testing, also called genetic mutation testing or genomic testing, looks at the specific mutations in tumor cells. These biomarkers can then be used to determine the best treatment options for a lung cancer patient.

At the CURE® Educated Patient® Lung Cancer Summit in December 2020, Dr. Melissa Johnson discussed different biomarkers that can impact small cell lung cancer patient’s decisions. Her main focus was on the widespread PD-L1 tumor mutation burden and microsatellite instability (MSI). They play an important role in determining immunotherapy treatment for patients with SCLC.

Tumors that have high PD-L1 expression from the outset are more likely to respond to immunotherapy. This response makes it possible to initially treat these patients with immunotherapy drugs to

  • reduce symptoms
  • improve energy
  • avoid the side effects of chemotherapy

Genetic Factors

The genetic determinants of small cell lung cancer have not received much attention because an outsized number of cases are attributed to smoking. But a new study from the Center for Cancer Research identified specific inherited mutations that increase an individual’s risk of developing SCLC.

The study found patients with inherited mutations had a better prognosis than patients without the mutation. They stayed in remission longer than their counterparts following standard platinum-based chemotherapy. These patients may be more likely to benefit from chemotherapy and other treatments that exploit the cancer’s inability to repair damaged DNA.

 

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What to Expect

Receiving a diagnosis of small cell lung cancer (SCLC) can be a life-changing event, and it’s natural to have many questions about what to expect next. One of the first things that will happen is more tests. These tests are important because they help your doctors understand exactly where the cancer is and if it has spread to other parts of your body. This process is called staging, and it’s key to deciding the best treatment for you. With SCLC, there are two main stages: limited stage, where the cancer is only in one part of the chest, and extensive stage, where it has spread more widely. The staging helps your medical team tailor a treatment plan that might include chemotherapy, radiation, or a combination of both.

Your healthcare team will also discuss your treatment options with you. For small cell lung cancer, the treatments aim to control the cancer, help ease symptoms, and improve your quality of life. Chemotherapy is a common treatment for SCLC because this type of cancer tends to respond well to these drugs. Sometimes, doctors may also recommend radiation therapy, especially if the cancer is in the limited stage. They might even combine radiation with chemotherapy for a stronger attack on the cancer cells. And, as discussed above, sometimes chemotherapy is combined with immunotherapy for extensive stage SCLC patients. It’s important to talk openly with your doctors about the treatments, what they involve, and any side effects you might experience.

Finally, after starting treatment, you’ll have regular check-ups to see how well the treatment is working. These check-ups usually involve physical exams, blood tests, and imaging tests like CT scans or MRIs. They help your doctors keep an eye on the cancer and make changes to your treatment if necessary. Remember, every person’s journey with small cell lung cancer is unique, so your experience may vary. It’s crucial to have a good support system and to ask your healthcare team any questions you might have. They are there to help you through this journey every step of the way.

FDA-Approved Small Cell Lung Cancer Treatment

Types

  • Tarlatamab-dlle (Imdelltra)

    Tarlatamab is given to small cell lung cancer patients who have already tried chemotherapy but whose cancer has come back or spread.

    This injectable medicine is an antibody that targets a protein on cancer cells called DLL3. By attaching to DLL3, tarlatamab helps the body’s immune system find and destroy the cancer cells. In a clinical trial, some patients who received tarlatamab had their tumors shrink or disappear for some time.

    Approved for: SCLC

    Biomarkers: SCLC

    FDA Approval Date: 05/16/2024

    Used in: SCLC

  • Nivolumab (Opdivo/Opdivo Injection)

    Nivolumab (Opdivo/Opdivo Injection) is a FDA-approved CombinationTherapy for Small cell lung cancer (SCLC) that has metastasized. It is used in patients whose cancer got worse after treatment with platinum chemotherapy and at least one other therapy.

    Approved for: SCLC

    Biomarkers: SCLC

    FDA Approval Date: 08/01/2018

    Used in: SCLC

  • Lurbinectedin (Zepzelca)

    Small cell lung cancer that is metastatic. It is used in adults whose disease has gotten worse during or after treatment with platinum chemotherapy. *This use is approved under FDA’s Accelerated Approval Program. As a condition of approval, a confirmatory trial(s) must show that lurbinectedin provides a clinical benefit in these patients.*

    Approved for: SCLC

    Biomarkers: SCLC

    FDA Approval Date: 12/28/2024

    Used in: SCLC

  • Doxorubicin Hydrochloride (Totect/Zinecard)

    Doxorubicin is a chemotherapy drug used in treating both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). For SCLC, it is often part of combination therapy, particularly effective in extensive-stage cases where the cancer has spread beyond the lungs, and can be added when other treatments are insufficient. In NSCLC, doxorubicin typically works alongside other chemotherapy drugs, especially beneficial for certain subtypes and when targeted therapies are not viable. Non-small cell lung cancer that is metastatic. Small cell lung cancer that is metastatic.

    Approved for: NSCLC, SCLC

    FDA Approval Date: 01/01/1974

    Used in: Chemotherapy, SCLC

  • Methotrexate Sodium (Trexall/Xatmep)

    Methotrexate has been a key player in cancer treatment for decades, particularly for lung cancer. It works by inhibiting the enzyme dihydrofolate reductase, which is essential for DNA synthesis and cell division, effectively slowing or stopping the growth of cancer cells. Often used in combination with other drugs, methotrexate is especially beneficial in advanced stages of lung cancer and can serve as an option for cases resistant to other treatments. First approved by the FDA in 1953, its long-standing track record has provided a solid understanding of its effects over more than 70 years.

    Approved for: NSCLC, SCLC

    FDA Approval Date: 01/01/1953

    Used in: Adjuvant Therapy, Chemotherapy, Combination Therapy, SCLC

  • Carboplatin (Paraplatin)

    Carboplatin, also known as Paraplatin, is a chemotherapy drug used in the treatment of lung cancer, effective against both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). It disrupts the DNA replication in cancer cells, leading to their death. It can be employed as part of combination chemotherapy to enhance effectiveness, used after surgery to eliminate residual cancer cells, or given before surgery to shrink tumors for improved surgical outcomes. Additionally, carboplatin plays a role in palliative care for advanced lung cancer. First approved by the FDA in 1989, it has a proven track record in clinical practice over the past three decades.

    Approved for: NSCLC, SCLC

    Biomarkers: SCLC

    FDA Approval Date: 01/01/1989

    Used in: Adjuvant Therapy, Combination Therapy, SCLC

  • Topotecan Hydrochloride (Hycamtin)

    Topotecan hydrochloride, marketed as Hycamtin, is a chemotherapy drug primarily used in the treatment of small cell lung cancer (SCLC). The FDA first approved topotecan in 1996 for the treatment of patients with SCLC after disease progression following initial chemotherapy. It works as a topoisomerase I inhibitor, interfering with DNA replication in cancer cells. Topotecan is typically used in the second-line setting for SCLC patients whose disease has recurred or progressed after first-line treatment. It can also be considered in combination with other agents in certain cases.

    Approved for: SCLC

    Biomarkers: SCLC

    FDA Approval Date: 01/01/1996

    Used in: SCLC