If you’ve been diagnosed with advanced non-small cell lung cancer (NSCLC), there are several lung cancer treatment options available for you. In recent years, the U.S. Food and Drug Administration (FDA) has approved several new treatments for advanced NSCLC. Some of these include surgery, chemotherapy, radiation, targeted therapy, and immunotherapy. Your oncologist (doctor specializing in treating cancer) will discuss with you which options are best.

Lung cancer is the second most common cancer in the United States and leading cause of cancer-related deaths across all sexes. Non-small cell lung cancer is the most common type of lung cancer, accounting for about 80 percent to 85 percent of all cases. NSCLC is difficult to catch early because there are little to no symptoms in the early stages. As a result, most cases aren’t caught until they have reached advanced stages — stage 3 or stage 4. In these stages, the cancer has spread beyond the location of the original tumor. (Cancer stages are commonly rendered using Roman numerals, e.g., “stage III” instead of “stage 3.”)

Treatment options depend on factors including staging, the size of the original tumor, where it is located, and where cancer has spread, as well as your overall health.

Treatment options for advanced NSCLC depend on many factors, including:

• The specific NSCLC subtype (such as adenocarcinoma, squamous cell carcinoma, or large cell carcinoma)​
• Cancer staging (how far the cancer has spread)​
• Tumor size and location
• Where the cancer has spread (such as lymph nodes, brain, bones, or liver)​
• Your overall health and lung function
• How well you tolerate treatment

Doctors also consider your overall health, lung function, and how well you’ve been tolerating treatment when making treatment decisions.

1. Surgery for Advanced NSCLC

Surgery is sometimes used for stage 3A NSCLC, but it is not commonly used for later stages. Treatment for stage 3A often begins with chemotherapy and may also include immunotherapy or radiation therapy. If the doctor believes surgery can remove your remaining cancer and you are healthy enough, they may recommend surgery. Options include a lobectomy (removal of part of the lung) or, in some cases, a pneumonectomy (removal of the entire lung).

Surgery isn’t usually recommended for stage 3B or stage 4 NSCLC because the cancer has often spread too far to be removed completely​. Instead, doctors often combine other treatments, such as chemotherapy, immunotherapy, and radiation therapy, to help shrink or control the cancer. When surgery is performed, these treatments may also be used before or after the operation to kill any remaining cancer cells that could not be safely removed​.

2. Chemotherapy for Advanced NSCLC

Chemotherapy is a type of cancer treatment that uses powerful drugs to kill rapidly dividing cells, including cancer cells​. Because of its strong effects and potential side effects, chemotherapy is usually not recommended for people with poor overall health.

Chemotherapy drugs are given through an intravenous (IV) infusion or taken orally (by mouth). They may be used alone or in combination, depending on the treatment plan. Once in the bloodstream, chemotherapy travels throughout the body to attack cancer cells wherever they may be​.

Some chemotherapy drugs are specifically approved for treating NSCLC, while others are used off-label — meaning they are FDA-approved for other cancers but may still be effective for NSCLC based on research and clinical experience. Doctors may prescribe off-label chemotherapy if standard treatments are not working, if the cancer has unique characteristics that suggest a particular drug may help, or if emerging research supports its use.

Some examples of chemotherapy treatments used for NSCLC include:

• Carboplatin (off-label)
• Cisplatin (off-label)
• Docetaxel (Docivyx)
• Etoposide (Toposar, off-label)
• Gemcitabine (Infugem, Gemzar)
• Nab-paclitaxel (Abraxane)
• Paclitaxel
• Pemetrexed (Alimta, Axtle, Pemfexy, Pemrydi)
• Vinorelbine (Navelbine)

Side Effects of Chemotherapy for Advanced NSCLC

Chemotherapy can’t always tell the difference between cancer cells and normal cells that also divide quickly, which is why it can affect healthy parts of the body​. Some normal cells that divide rapidly include:

• Hair follicles
• Blood-forming cells in the bone marrow
• Cells lining the digestive tract and mouth

Since chemotherapy also kills these healthy cells, side effects can include:

• Hair loss
• Decreased blood cell counts leading to bruising or infections
• Nausea, diarrhea, and vomiting

Your doctor may prescribe medications to help manage these side effects. Many side effects improve after treatment ends, but it’s important to discuss any concerns with your cancer care team​.

3. Radiation Therapy for Advanced NSCLC

Radiation therapy (also known as radiotherapy) uses high-energy beams to kill cancer cells and shrink tumors. The type of radiation is similar to that used in X-rays, but it’s much more concentrated for cancer treatment.

This therapy works by damaging the DNA of cancer cells beyond repair, causing the cells to stop dividing or die. There are two types of radiation therapy used in the treatment of advanced NSCLC: external beam and internal beam radiation therapy.

External Beam Radiation

External beam radiation uses a radiation source on the outside of the body to focus on the cancer. During the procedure, you’ll lie on an examination table while a machine aims radiation at the tumor. This is the most common type of radiation for NSCLC. It can be used as:

• A main lung cancer treatment option, particularly if the tumor can’t be removed due to its location or size
• A treatment before surgery to shrink a lung tumor that may be difficult to operate on
• A treatment after surgery to kill any remaining cancer cells that cannot be removed safely during surgery
• A treatment for metastatic NSCLC (spread of cancer cells outside the lung) to bones, liver or the brain
• A treatment to relieve symptoms of advanced NSCLC, such as bleeding, pain, cough, and trouble swallowing, also known as palliative treatment

Internal Beam Radiation

Internal radiation therapy is also known as brachytherapy. It involves the placement of small, radioactive pellets directly into the cancer to help shrink a tumor. The doctor uses a special tool called a bronchoscope to see inside the airways and passageways of the lungs (known as bronchi and bronchioles) to place the pellets. The radiation can only travel a short distance from the source, so it is less likely to damage the surrounding healthy tissues. This is less commonly used than external beam radiation.

4. Immunotherapy for Advanced NSCLC

Immunotherapy is a relatively recent advancement in the treatment of cancer. It uses human-made antibodies (known as monoclonal antibodies) that help activate the immune system to target and kill cancer cells. Immunotherapy targets specific cells in the body, which prevents many side effects seen in treatments like chemotherapy.

Immunotherapy activates the immune system to target and kill cancer.

Immune checkpoint inhibitors (ICIs) are a type of immunotherapy used to treat advanced NSCLC. The immune system has natural “checkpoints” — proteins that regulate immune responses to prevent the immune system from mistakenly attacking healthy cells. Cancer cells exploit these checkpoints by sending “off signals” that deactivate immune cells, allowing tumors to grow unchecked. Checkpoint inhibitors block these signals so that the immune system can recognize and attack cancer cells.

One class of checkpoint inhibitors targets two checkpoint proteins: PD-1 and PD-L1. PD-1 is found on immune cells known as T cells, and PD-L1 is found on both normal cells and some cancer cells. Monoclonal antibodies have been developed to target either PD-1 or PD-L1, preventing interaction between the two proteins. As a result, the T cells can recognize the cancer cells and kill them, leading to the activation of a helpful immune response.

CTLA-4 inhibitors are another class of checkpoint inhibitors for NSCLC. These monoclonal antibodies target CTLA-4, a protein that blocks T-cell activity.

Checkpoint inhibitors that are used to treat advanced NSCLC include:

• Atezolizumab (Tecentriq), which targets PD-L1
• Cemiplimab (Libtayo), which targets PD-L1
• Durvalumab (Imfinzi), which targets PD-L1
• Ipilimumab (Yervoy), which targets CTLA-4
• Nivolumab (Opdivo), which targets PD-1
• Pembrolizumab (Keytruda), which targets PD-1

Immunotherapy is usually given through an IV line. Treatments can last a few hours and may be done every few weeks.

While immunotherapy is generally better tolerated than chemotherapy, it can still cause side effects, including:

• Fatigue
• Fever
• Skin rash

Serious side effects are rare but may include inflammation in the lungs, liver, or other organs. It’s important to tell your doctor about any new or worsening symptoms​.

5. Targeted Therapy for Advanced NSCLC

Targeted therapy refers to a class of drugs that work by identifying specific mutations (changes) or growth factors in cancer cells and damaging or destroying them. Because these drugs are so specific, they help minimize damage to other cells and often cause fewer side effects. For advanced NSCLC, several new types of targeted therapies are available.

Small Molecule Inhibitors

Small molecule inhibitors can be used to target specific mutations in cancer. One example is tyrosine kinase inhibitors (TKIs), named after the proteins they target in cells. In cases of NSCLC, there are common genetic mutations that can lead to developing cancer. These include:

• Epidermal growth factor receptor (EGFR), found in 10 percent of NSCLC cases, particularly lung adenocarcinoma
• The fusion of anaplastic lymphoma kinase (ALK) with the EML4 gene, found in 5 percent of NSCLC cases
• A KRAS gene mutation, found in about 25 percent of NSCLC cases

Targeted therapies identify specific mutations or growth factors in cancer cells and destroy them. Because these drugs are so specific, they help minimize damage to healthy cells and often cause fewer side effects.

These genes are all involved in specialized signaling pathways that normally tell healthy cells when to grow and divide. However, when they become mutated, these signals cannot be shut off. The cancer cells are then able to grow and divide uncontrollably, creating a tumor.

If you have one of these mutations, you can be treated with targeted therapy. These drugs need a genetic mutation to target in order to work. A doctor can identify these mutations through DNA sequencing of the tumor or the blood. Several new drugs have been approved for treating NSCLC containing specific mutations.

For EGFR mutations, the approved treatments include:

• Afatinib (Gilotrif)
• Erlotinib
• Gefitinib (Iressa)
• Osimertinib (Tagrisso)

For EML4-ALK fusions, available treatments include:

• Alectinib (Alecensa)
• Crizotinib (Xalkori)
• Ceritinib (Zykadia)

For KRAS mutations, options include Adagrasib (Krazati) and Sotorasib (Lumakras).

Angiogenesis Inhibitors

Vascular endothelial growth factor (VEGF) initiates the growth of new blood vessels in the body. This process is called angiogenesis. Large tumors need their own blood supply to take in oxygen and nutrients. Cancer cells sometimes learn to make their own VEGF to grow new vessels.

Bevacizumab (Avastin, Mvasi, Vegzelma, Zirabev) and ramucirumab (Cyramza) are monoclonal antibody drugs that prevent VEGF from binding to its receptor. By doing this, it stops new blood vessels from forming.

New lung cancer treatment options are on the horizon. If you want to learn more about what types of therapies are available, talk with your healthcare team. They can give you the best recommendations for your specific situation.

Finding Support With NSCLC

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