Systemic therapy is a type of treatment that affects the entire body rather than just one part. This can include chemo- and immunotherapy. Radiation therapy is not a systemic therapy, as it targets a specific point in the body. Systemic therapy can be an option for people in the later stages of non-small cell lung cancer (NSCLC), for it may prevent or slow the spread of the cancer.

Although there are several types of lung cancer, small-cell lung cancer (SCLC) and NSCLC account for around 95% of all lung cancers. SCLC only affects smaller lung cells.

Stage 4 NSCLC is the most advanced stage of this condition. It means there is a high risk of the cancer spreading to other parts of the body. Although stage 4 NSCLC is not curable, doctors can recommend a variety of systemic therapies that can slow the progression of the disease and improve a person’s outlook.

This article will look at stage 4 NSCLC and explain what systemic cancer therapies do. It will also list some types of systemic therapies for stage 4 NSCLC, provide examples of them, and explore how effective they can be.

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The body consists of millions of individual cells that are constantly growing and dying off. Lung cancer occurs when cells in a person’s lungs grow in unusual and uncontrolled ways.

Like many other cancer types, lung cancer can lead to the development of cancerous tumors in the body. These large lumps of tissue can damage the organs in which they grow.

Stages explained

NSCLC comes in various stages. The most advanced stage of NSCLC is stage 4. However, doctors also distinguish between stage 4A and stage 4B NSCLC.

  • Stage 4A NSCLC: This is the earlier sub-stage of stage 4 NSCLC. According to the National Cancer Institute (NCI), stage 4A NSCLC is when the condition has led to all or some of the following:
    • Both lungs contain at least one tumor.
    • The fluid around the heart or lungs contains cancer cells.
    • Cancer nodules exist in the lungs’ lining or in the sac around the heart.
    • The cancer has spread to one location in an organ that is far away from the lungs.
  • Stage 4B NSCLC: This is the later sub-stage of stage 4 NSCLC. It occurs when the cancer has spread to multiple locations across one or more organs, which must be far away from the lungs. These organs include:
    • the brain
    • the adrenal gland
    • the kidneys
    • the liver
    • distant lymph nodes
    • bones

Learn more about the different stages of lung cancer here.

Systemic therapy explained

As with most cancers, doctors have a variety of treatment options to choose from. They include some systemic cancer therapies.

The NCI describes systemic treatment as involving any substance that travels through a person’s bloodstream, reaching and affecting cells throughout the body, with the aim of stopping the growth of cancer cells.

Doctors usually use chemotherapy, targeted therapies, or immunotherapy as systemic therapy for stage 4 NSCLC. They may also use several of these therapies at once.

Surgical procedures and radiation therapy do not count as systemic cancer therapies.

Healthcare professionals may recommend different combinations of treatment for people with NSCLC. A person can discuss the side effects of each treatment with a doctor.

Chemotherapy involves regularly taking specialized anti-cancer drugs either orally or intravenously. Scientists have developed these drugs to seek out and attack cancer cells by stopping their growth or division.

At stage 4 of NSCLC, there is no cure for the disease. Therefore, a person will need to discuss the pros and cons of chemotherapy with a doctor. If a person has a low performance status, which means they are able to live as normally as possible, they may decide to choose chemotherapy as a treatment option.

If a doctor believes the process and side effects of chemotherapy may be too aggressive for a person at this stage, they may recommend palliative care options instead.

Examples

There are many kinds of chemotherapy drugs, and they affect cancer cells in different ways. Some common types of chemotherapy drugs include:

  • alkylating agents, such as chlormethine and chlorambucil
  • antimetabolites, including methotrexate and gemcitabine
  • mitotic inhibitors, such as vinblastine and paclitaxel
  • antibiotics, such as actinomycin D and bleomycin
  • antibodies, including bevacizumab and rituximab

Effectiveness

It is difficult to know exactly how effective these drugs can be at this stage of the condition, as many doctors recommend using multiple chemotherapy drugs at once.

However, authors of a 2016 paper looked at several different studies, each of which investigated the effectiveness of the drugs cisplatin or carboplatin on stage 4 NSCLC. In each of these studies, researchers combined the cisplatin or carboplatin with some of the following medications:

  • paclitaxel
  • gemcitabine
  • docetaxel
  • vinorelbine
  • irinotecan
  • pemetrexed

The authors of the paper found that the median overall survival period for people taking these drug combinations was positive, at around 8–10 months.

Learn more about the success rate of chemotherapy for lung cancer here.

Many cancers develop due to genetic mutations, which are changes in a person’s genes. Since genes act as instructions for cell division and growth, some genetic mutations can lead to the formation of tumors.

With genetic testing, doctors can sometimes find out which genetic mutations are causing a person’s NSCLC. They can then use targeted tyrosine kinase inhibitors (TKIs) to treat NSCLC. TKIs are drugs that make it hard for specific genes and proteins to do their jobs.

Learn more about how targeted therapy for lung cancer works here.

Examples

Different TKIs will target different genetic mutations. The NCI lists the following as common TKIs:

  • EGFR inhibitors, including erlotinib and gefitinib
  • BRAF inhibitors, such as dabrafenib
  • ALK inhibitors, including ceritinib and lorlatinib
  • RET inhibitors, such as selpercatinib
  • NTRK inhibitors, including larotrectinib
  • ROS1 inhibitors, such as crizotinib and entrectinib

Effectiveness

Targeted therapy can improve the outlook for individuals with stage 4 NSCLC. For example, a 2019 study found that people with an ALK mutation who took crizotinib lived longer than those receiving chemotherapy.

Targeted therapy is a quickly changing area of ongoing research. There are numerous clinical trials a person can discuss with a doctor to learn about the pros and cons of joining.

Immunotherapy is a newer treatment option for people with lung cancer. It involves taking medications that affect a person’s immune system, which protects their body from disease. Doctors sometimes treat stage 4 NSCLC with immune checkpoint inhibitors (ICIs).

ICIs work to inhibit proteins known as checkpoints, which keep immune system cells from being too strong. When ICIs have inhibited some checkpoints, immune system cells can sometimes attack cancer cells.

There are other types of immunotherapy for lung cancer, including adoptive T cell therapy, immune system modulators, and therapeutic vaccines.

Learn about various types of immunotherapy for lung cancer here.

Examples

There are many different ICIs, including:

Effectiveness

In a 2020 review, researchers hail immunotherapy as a breakthrough in lung cancer treatment.

It can have a long-term effect on cancer, because it teaches the immune system to find and kill cancer cells. This means that its effects last even after the treatment has left a person’s body, which is not the case with chemotherapy.

Although doctors often use ICIs to treat stage 4 NSCLC, authors of a 2021 review call for more research on the effectiveness of this systemic therapy. In particular, there is no solid evidence that ICIs can help people whose NSCLC is significantly affecting their quality of life.

Systemic therapies target the whole body rather than the specific area where the cancer has developed. It can help people with stage 4 NSCLC, because it can stop or slow the spreading of the cancer.

However, stage 4 NSCLC is not curable. Therefore, a person will need to discuss the pros and cons of potentially aggressive treatment with a doctor.

Systemic therapy is an area of ongoing research. As science progresses, researchers are developing ever more effective techniques for treating this condition.