Cancer is a term that is broadly used to describe a collection of more than a hundred related diseases that lead to the uncontrolled growth of abnormal cells in the affected organs.
The human body is made up of a trillion cells, the ‘building blocks of life’ that constitute the basic structural units of any organism. These cells grow and divide to form new ones. When they grow old or get damaged, they die and new cells form in their place.
If this pattern gets disrupted due to genetic changes, cancer develops. The old and damaged cells don’t die, while new ones multiply, hence creating an uncontrolled growth of abnormal cells.
The continuous division of these cells could form masses of tissue, which become a tumour. These can be benign or cancerous. If benign, the tumour can grow but does not spread. Mostly, this can be removed and may not grow back. If cancerous, the tumour can spread to other parts of the body. This is called metastasis, and endangers life as the cancer could spread to vital organs like the brain, lungs, liver etc. and damage the vital functions necessary to sustain life.
Cancer is a term that is broadly used to describe a collection of more than a hundred related diseases that lead to the uncontrolled growth of abnormal cells in the affected organs.
The lungs are an essential part of the respiratory system. The respiratory system consists of a pair of lungs that also have different parts. The right lung has three lobes, and the left lung has two. A thin layer called the pleura to protect the lungs. Cells in the lungs do tend to change and can grow or stop behaving normally. Some of these cells can grow into benign, non-cancerous tumours or malignant tumours. These cells can destroy the nearby tissue and can also spread to other parts of the body, causing lung cancer.
Lung cancers can be primary and secondary, depending on the location that it starts. Primary tumours in the lungs start locally, and secondary ones start in another part of the body and spread to the lungs. It is also further divided into non-small cell lung cancer and small cell lung cancer, depending on the appearance of the cancer cells under the microscope.
Types of lung cancer
The lungs are part of the respiratory system. The cells in the lungs do tend to change and can grow or stop behaving normally. Some of these cells can grow into noncancerous benign tumours, and some can grow into cancer. These cells can destroy the nearby tissue and can also spread to other parts of the body — lung cancer comprises of different types and grades. The type of lung cancer that a person has can help doctors understand the cell that cancer started in. Lung cancer is of two common types, small cell lung cancer, and non-small cell lung cancer. Lung cancer can also be of the primary and secondary type depending on the origin of cancer. Primary lung cancer is the one that starts in the lungs, and secondary lung cancer is the kind of cancer that starts in another part of the body and spreads to the lungs.
There are 2 main classifications of lung cancer: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). These 2 types are treated differently.
Small cell lung cancer
SCLC begins when healthy cells in the lung change and grow out of control, forming a mass called a tumour, a lesion, or a nodule. SCLC begins in the nerve cells or hormone-producing cells of the lung. The term “small cell” refers to the size and shape of the cancer cells as seen under a microscope. This type of cancer has been characterized by small cells that multiply very quickly and form large tumours that spread throughout the body. This kind of cancer is common among smokers. Also called oat-cell cancer; it constitutes about 10-15% of all lung cancer. A tumour can be cancerous or benign. Once a cancerous lung tumour grows, it may or may not shed cancer cells. These cells can be carried away in blood or float away in the fluid, called lymph, that surrounds lung tissue. Lymph flows through tubes called lymphatic vessels that drain into collecting stations called lymph nodes. Lymph nodes are the tiny, bean-shaped organs that help fight infection. They are located in the lungs, the centre of the chest, and elsewhere in the body. The natural flow of lymph out of the lungs is toward the centre of the chest, which explains why SCLC often spreads there first. When a cancer cell moves into a lymph node or to a distant part of the body through the bloodstream, it is called metastasis.
Non-small cell lung cancer
Non-small cell lung cancer constitutes about 80% of the lung cancer cases, and it further comprises four different types depending on the cell of origin.
NSCLC begins when healthy cells in the lung change and grow out of control, forming a mass called a tumour, a lesion, or a nodule. A lung tumour can begin anywhere in the lung. A tumour can be cancerous or benign. Once a cancerous lung tumour grows, it may shed cancer cells. These cells can be carried away in blood or float away in the fluid, called lymph, that surrounds lung tissue. Lymph flows through tubes called lymphatic vessels that drain into collecting stations called lymph nodes.
Lymph nodes are the small, bean-shaped organs that help fight infection. They are located in the lungs, the centre of the chest, and elsewhere in the body. The natural flow of lymph out of the lungs is toward the centre of the chest, which explains why lung cancer often spreads there first. When a cancer cell moves into a lymph node or to a distant part of the body through the bloodstream, it is called metastasis.
Types of NSCLC
NSCLC begins in the epithelial cells. It is important for doctors to distinguish between lung cancer that begins in the squamous cells from lung cancer that begins in other cells. This information is used to determine treatment options.
Your doctor will determine which type of NSCLC you have based on the way cancer looks under a microscope. The different types of NSCLC are:
- Squamous cell carcinoma
- Large cell carcinoma
- NSCLC-NOS (not otherwise specified) or NSCLC undifferentiated
Adenocarcinoma forms the mucus-producing glands and is the most common in women and non-smokers.
Bronchi alveolar carcinoma
This type of cancer forms near the air sacs of the lungs
Squamous cell carcinoma
Squamous cell carcinoma forms in the lining of the bronchial tubes, commonly seen in smokers.
Large cell carcinoma
Large cell carcinomas form near the outer edges or surface of the lungs. This type of cancer is rare.
Other types of lung cancer
Pancoast tumours are the kind that affects the top part of the lungs.
Mesothelioma is the kind of cancer that affects the covering (the pleura) of the lungs.
In general, a lower number stage of cancer is linked with a better outcome. However, no doctor can predict how long a patient will live with cancer-based only on the stage of disease because it is different in each person, and treatment works differently for each tumour.
Cancer stages-Small Cell Lung Cancer
The most common way doctors stage SCLC is by classifying the disease as limited stage or extensive stage.
- Limited stage.Limited stage means that the cancer is only in 1 part of the chest and radiation therapy could be a treatment option. About 1 out of 3 people with SCLC have limited stage disease when first diagnosed.
- Extensive stage. The extensive stage is used to describe SCLC that has spread to parts of the body such as the other lung, bone, brain, or bone marrow. Many doctors consider SCLC that has spread to the fluid around the lung to be extensive stage as well. About 2 out of 3 people with SCLC have an extensive disease when the cancer is first found.
There is another, more formal system to describe the stage of lung cancer, but SCLC is almost always staged as limited or extensive stage as described above. The other, less commonly used staging system gives a number, 0 through 4, based on whether the tumour can be completely removed by a surgeon.
A stage I lung cancer is a small tumour that has not spread to any lymph nodes, making it possible for a surgeon to completely remove it. Stage I is divided into 2 sub-stages based on the size of the tumour:
- Stage IA tumours are 3 centimetres (cm) or less in size. Stage IA tumours may be further divided into IA1, IA2, or IA3 based on the size of the tumour.
- Stage IB tumours are more than 3 cm but 4 cm or less in size.
Stage II lung cancer is divided into 2 sub-stages:
- A stage IIA cancer describes a tumour larger than 4 cm but 5 cm or less in size that has not spread to the nearby lymph nodes.
- Stage IIB lung cancer describes a tumour that is 5 cm or less in size that has spread to the lymph nodes. Or a stage IIB cancer can be a tumour more than 5 cm wide that has not spread to the lymph nodes.
Stage III lung cancers are classified as either stage IIIA, IIIB, or IIIC. The stage is based on the size of the tumour and which lymph nodes cancer has spread to. Stage III cancers have not spread to other distant parts of the body.
Stage IV means the lung cancer has spread to more than 1 area in the other lung, the fluid surrounding the lung or the heart, or distant parts of the body through the bloodstream. Once cancer cells get into the blood, cancer can spread anywhere in the body. Stage IV is divided into 2 sub-stages:
- Stage IVA cancer has spread within the chest and/or has spread to 1 area outside of the chest.
- Stage IVB has spread outside of the chest to more than 1 place in 1 organ or to more than 1 organ.
Cancer Stages- Non-Small Cell Lung Cancer
Staging is a way of describing where the cancer is located, if or where it has spread, and whether it is affecting other parts of the body. Doctors use diagnostic tests to find out cancer’s stage, so staging may not be complete until all of the tests are finished. Knowing the stage helps the doctor to decide what kind of treatment is best and can help predict a patient’s prognosis, which is the chance of recovery. There are different stage descriptions for different types of cancer.
In general, a lower number stage of NSCLC is linked with a better outcome. However, no doctor can predict how long a patient will live with lung cancer based only on the stage of the disease. This is because lung cancer is different in each person and treatment works differently for each tumour.
The stage of NSCLC is based on a combination of several factors, including:
- The size and location of the tumour
- Whether it has spread to the lymph nodes and/or other parts of the body.
There are 5 stages for NSCLC: stage 0 (zero) and stages I through IV (1 through 4).
This is called in situ disease, meaning the cancer is “in place” and has not grown into nearby tissues and spread outside the lung.
A stage I lung cancer is a small tumour that has not spread to any lymph nodes, making it possible for a surgeon to completely remove it. Stage I is divided into 2 substages based on the size of the tumour:
Stage IA tumours are 3 centimetres (cm) or less in size. Stage IA tumours may be further divided into IA1, IA2, or IA3 based on the size of the tumour.
Stage IB tumours are more than 3 cm but 4 cm or less in size.
Stage II lung cancer is divided into 2 substages:
A stage IIA cancer describes a tumour larger than 4 cm but 5 cm or less in size that has not spread to the nearby lymph nodes.
Stage IIB lung cancer describes a tumour that is 5 cm or less in size that has spread to the lymph nodes. A stage IIB cancer can also be a tumour more than 5 cm wide that has not spread to the lymph nodes.
Sometimes, stage II tumours can be removed with surgery, and other times, more treatments are needed.
Stage III lung cancers are classified as either stage IIIA, IIIB, or IIIC. The stage is based on the size of the tumour and which lymph nodes the cancer has spread to. Stage III cancers have not spread to other distant parts of the body.
For many stage IIIA and stage IIIB cancers, the tumour may be difficult or sometimes impossible, to remove with surgery. Stage IIIC cancers cannot be removed with surgery. For example, lung cancer may have spread to the lymph nodes located in the centre of the chest, which is outside the lung. Or the tumour may have grown into nearby structures in the lung. In either situation, it is less likely that the surgeon can completely remove cancer. Stage III cancers that cannot be treated with surgery can often be successfully treated with systemic therapy and radiation therapy (see Types of Treatment).
Stage IV means the lung cancer has spread to more than 1 area in the other lung, the fluid surrounding the lung or the heart, or distant parts of the body through the bloodstream. Once cancer cells get into the blood, cancer can spread anywhere in the body. But, NSCLC is more likely to spread to the brain, bones, liver, and adrenal glands. Stage IV NSCLC is divided into 2 substages:
Stage IVA cancer has spread within the chest and/or has spread to 1 area outside of the chest.
Stage IVB has spread outside of the chest to more than 1 place in 1 organ or to more than 1 organ.
In general, surgery is not an option for most stage IIIB, IIIC, or IV lung cancers. Lung cancer can also be impossible to remove if it has spread to the lymph nodes above the collarbone.
Symptoms and signs-Small Cell Lung Cancer:
People with SCLC may experience the following symptoms or signs. Sometimes people with SCLC do not have any of these changes, but SCLC often causes these symptoms to worsen over weeks or sometimes days.
- Shortness of breath
- Chest pain
- Loss of appetite
- Unexplained weight loss
- Coughing up phlegm or mucus
- Coughing up blood
- Swelling of the neck or face
Symptoms and signs– Non-Small Cell Lung Cancer:
People with NSCLC may experience the following symptoms or signs. Sometimes people with NSCLC do not have any of these changes. Or, the cause of a symptom may be a different medical condition that is not cancer.
- Shortness of breath
- Chest pain, if a tumour spreads to the lining of the lung or other parts of the body near the lungs
- Loss of appetite
- Coughing up phlegm or mucus
- Coughing up blood
- Unintentional weight loss
Doctors use many tests to find or diagnose, cancer. They also do tests to learn if cancer has spread to another part of the body from where it started. If this happens, it is called metastasis. For example, imaging tests can show if cancer has spread, but they can never be used alone to diagnose.
Imaging tests show pictures of the inside of the body. Doctors may also do tests to learn which treatments could work best.
For most types of cancer, a biopsy is the only sure way for the doctor to know if an area of the body has cancer. In a biopsy, the doctor takes a small sample of tissue for testing in a laboratory. If a biopsy is not possible, the doctor may suggest other tests that will help make a diagnosis
Imaging scans are very important in the care of people with NSCLC. However, no test is perfect. Only a biopsy can do that. Chest x-ray and scan results must be combined with a person’s medical history, a physical examination, blood tests, and information from the biopsy to form a complete story about where cancer began and if or where it has spread.
Here is a list of tests available to Diagnose Lung Cancer:
CT scan: A CT scan produces images that allow doctors to see the size and location of a lung tumour and/or lung cancer metastases. A CT scan takes pictures of the inside of the body using x-rays taken from different angles. A computer combines these pictures into a detailed, 3-dimensional image that shows any abnormalities or tumours. A CT scan can be used to measure the tumour’s size. Sometimes, a special dye called a contrast medium is given before the scan to provide better detail on the image. This dye can be injected into a patient’s vein or given as a pill or liquid to swallow.
Positron emission tomography (PET) scan: A PET scan is usually combined with a CT scan (see above), called a PET-CT scan. However, you may hear your doctor refer to this procedure just as a PET scan. A PET scan is a way to create pictures of organs and tissues inside the body. A small amount of a radioactive sugar substance is injected into the patient’s body. This sugar substance is taken up by cells that use the most energy. Because cancer tends to use energy actively, it absorbs more of the radioactive substance. A scanner then detects this substance to produce images of the inside of the body.
Magnetic resonance imaging (MRI) scan: An MRI also produces images that allow doctors to see the location of a lung tumour and/or lung cancer metastases and measure the tumour’s size. An MRI uses magnetic fields, not x-rays, to produce detailed images of the body. A special dye called a contrast medium is given before the scan to create a clearer picture. This dye can be injected into a patient’s vein or given as a pill or liquid to swallow. However, MRI scanning does not work well to take pictures of parts of the body that are moving, like your lungs, which move with each breath you take. For that reason, MRI is rarely used to look at the lungs. It may be helpful to find lung cancer that has spread to the brain or bones.
Bone scan: A bone scan uses a radioactive tracer to look at the inside of the bones. The tracer is injected into a patient’s vein. It collects in areas of the bone and is detected by a special camera. Healthy bone appears lighter to the camera, and areas of injury, such as those caused by cancer, stand out on the image. PET scans (see above) have been replacing bone scans to find NSCLC that has spread to the bones.
The procedures that doctors use to collect tissue to diagnose lung cancer and plan treatment are listed below:
Biopsy: A biopsy is the removal of a small amount of tissue for examination under a microscope. It is helpful to have a larger tumour sample to determine the subtype of NSCLC and do additional molecular testing (see below). If not enough of the tumour is removed to do these tests, another biopsy may be needed. After the biopsy, a pathologist analyzes the sample(s). A pathologist is a doctor who specializes in interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease.
Bronchoscopy: In a bronchoscopy, the doctor passes a thin, flexible tube with a light on the end into the mouth or nose, down through the main windpipe, and into the breathing passages of the lungs. A surgeon or a pulmonologist may perform this procedure. A pulmonologist is a medical doctor who specializes in the diagnosis and treatment of lung disease. The tube lets the doctor see inside the lungs. Tiny tools inside the tube can take samples of fluid or tissue so the pathologist can examine them. Patients are given mild anaesthesia during a bronchoscopy. Anaesthesia is medication to block the awareness of pain.
Needle aspiration/core biopsy: After numbing the skin, a special type of radiologist, called an interventional radiologist, removes a sample of the lung tumour for testing. This can be done with a smaller needle or a larger needle depending on how large a sample is needed. The doctor uses the needle to remove a sample of tissue for testing. Often, the radiologist uses a chest CT scan or special x-ray machine called a fluoroscope to guide the needle. In general, a core biopsy provides a larger amount of tissue than a needle aspiration. As explained above, doctors have learned that more tissue is needed in NSCLC for diagnosis and molecular testing.
Thoracentesis: After numbing the skin on the chest, a needle is inserted through the chest wall and into the space between the lung and the wall of the chest where fluid can collect. The fluid is removed and checked for cancer cells by the pathologist.
Thoracoscopy: This procedure is performed in the operating room, and the patient receives general anaesthesia. Through a small cut in the skin of the chest wall, a surgeon can insert a special instrument and a small video camera to assist in the examination of the inside of the chest. Patients need general anaesthesia for this procedure, but recovery time may be shorter with a thoracoscopy because of the smaller incisions that are used. This procedure may be referred to as video-assisted thoracoscopic surgery or VATS.
Mediastinoscopy: This is a surgical procedure performed in the operating room, and the patient receives general anaesthesia. A surgeon examines and takes a sample of the lymph nodes in the centre of the chest underneath the breastbone by making a small incision at the top of the breastbone. This procedure also requires general anaesthesia and is done in an operating room.
Thoracotomy: This procedure is performed in an operating room, and the patient receives general anaesthesia. A surgeon then makes an incision in the chest, examines the lung directly, and takes tissue samples for testing. A thoracotomy is the procedure surgeons most often use to completely remove a lung tumour.
Molecular testing of the tumour
Your doctor may recommend running tests on a tumour sample to identify specific genes, proteins, and other factors unique to the tumour.
There are several genes that may have changes, called mutations, in a lung tumour that can help cancer grow and spread. These mutations are found in the tumour and not in healthy cells in the body. This means that they are not inherited or passed down to your children.
Genetic mutations that are known to contribute to lung cancer growth often occur on 1 or more of several genes, including EGFR, ALK, KRAS, BRAF, HER2, ROS1, RET, MET, and TRK. Testing the tumour for some of these genes is now common for later-stage NSCLC. Testing for these genes may also be done for earlier stages of the disease.
Results from these tests can help determine if you can receive targeted therapy, which can be directed at specific mutations. Mutations for which targeted therapies exist are much more likely to occur in people with the adenocarcinoma type of NSCLC and who never smoked. The stage of NSCLC is also important for determining if you can receive targeted therapy.
Your doctor may also recommend PD-L1 testing. PD-L1 is a protein found on the surface of some cancer cells and some of the body’s immune cells. This protein stops the body’s immune cells from destroying cancer. Knowing if the tumour has PD-L1 helps your doctor decide if certain types of immunotherapy may be helpful. These types of immunotherapy block PD-L1 and allow the immune system to target cancer.
After diagnostic tests are done, your doctor will review all of the results with you. If the diagnosis is cancer, these results also help the doctor describe cancer.
In cancer care, different types of doctors often work together to create a patient’s overall treatment plan that combines different types of treatments. This is called a multidisciplinary team. Cancer care teams include a variety of other health care professionals, such as physician assistants, nurse practitioners, oncology nurses, social workers, pharmacists, counsellors, dietitians, and others.
There are 5 main ways to treat Lung Cancer
The goal of surgery is to completely remove the lung tumour and the nearby lymph nodes in the chest. The tumour must be removed with a surrounding border or margin of healthy lung tissue. A “negative margin” means that when the pathologist examined the lung or a piece of lung that was removed by the surgeon, no cancer was found in the healthy tissue surrounding the tumour. A surgical oncologist is a doctor who specializes in treating cancer using surgery. A thoracic surgeon is specially trained to perform lung cancer surgery.
The following types of surgery may be used for NSCLC:
Lobectomy. The lungs have 5 lobes, 3 in the right lung and 2 in the left lung. A lobectomy is the removal of an entire lobe of the lung. It is currently thought to be the most effective type of surgery, even when the lung tumour is very small.
A wedge resection. If the surgeon cannot remove an entire lobe of the lung, the surgeon can remove the tumour, surrounded by a margin of the healthy lung.
Segmentectomy. This is another way to remove cancer when an entire lobe of the lung cannot be removed. In a segmentectomy, the surgeon removes the portion of the lung where cancer developed.
Pneumonectomy. If the tumour is close to the centre of the chest, the surgeon may have to remove the entire lung.
The time it takes to recover from lung surgery depends on how much of the lung is removed and the health of the patient before surgery. Before surgery, talk with your health care team about the possible side effects from the specific surgery you will have.
Additional treatments can be given before and after your surgery to help lower the risk of recurrence.
Neoadjuvant therapy, also known as induction therapy, is a therapy given before your surgery. In addition to treating the primary tumour and lowering your risk of recurrence, this type of therapy is also used to help reduce the extent of surgery.
More commonly, you will receive adjuvant therapy. Adjuvant therapy is a treatment that is given after surgery. It is intended to get rid of any lung cancer cells that may still be in the body after surgery. This helps lower the risk of recurrence, though there is always some risk that cancer will come back.
Radiation therapy is the use of high energy x-rays or other particles to destroy cancer cells. If you need radiation therapy, you will see a specialist called a radiation oncologist. A radiation oncologist is a doctor who specializes in giving radiation therapy to treat cancer. The most common type of radiation treatment is called external-beam radiation therapy, which is radiation given from a machine outside the body. A radiation therapy regimen, or schedule, usually consists of a specific number of treatments given over a set period of time. This can vary from just a few days of treatment to several weeks.
Like surgery, radiation therapy cannot be used to treat widespread cancer. Radiation therapy only destroys cancer cells directly in the path of the radiation beam. It also damages the healthy cells in its path. For this reason, it cannot be used to treat large areas of the body.
Sometimes, CT scans (see Diagnosis) are used to plan out exactly where to direct the radiation beam to lower the risk of damaging healthy parts of the body. This is called intensity-modulated radiation therapy (IMRT) or stereotactic body radiation therapy (SBRT). It is not an option for all patients, but it may be used for early-stage disease and small tumours when surgery is not an option.
Some people with Stage I NSCLC or people who cannot have surgery may be treated with radiation therapy as an alternative treatment to surgery.
Side effects of radiation therapy
People with lung cancer who receive radiation therapy often experience fatigue and loss of appetite. If radiation therapy is given to the neck or centre of the chest, side effects can include a sore throat and difficulty swallowing. Patients may also notice skin irritation, similar to a sunburn, where radiation therapy was directed. Most side effects go away soon after treatment is finished.
If the radiation therapy irritates or inflames the lung, patients may develop a cough, fever, or shortness of breath months and sometimes years after the radiation therapy ends. About 15% of patients develop this condition, called radiation pneumonitis. If it is mild, radiation pneumonitis does not need treatment and goes away on its own. If it is severe, a patient may need treatment for radiation pneumonitis with steroid medications, such as prednisone (Rayos).
Radiation therapy may also cause permanent scarring of the lung tissue near where the original tumour was located. The scarring does not usually cause symptoms. However, severe scarring can cause a permanent cough and shortness of breath. For this reason, radiation oncologists carefully plan the treatments using CT scans of the chest to lessen the amount of healthy lung tissue exposed to radiation (see above).
Chemotherapy is the use of drugs to destroy cancer cells, usually by keeping the cancer cells from growing, dividing, and making more cells. It has been shown to improve both the length and quality of life for people with lung cancer of all stages.
A chemotherapy regimen, or schedule, usually consists of a specific number of cycles given over a set period of time. The type of lung cancer you have, such as adenocarcinoma or squamous cell carcinoma, affects which drugs are recommended for chemotherapy.
Common drugs used to treat lung cancer include either 2 or 3 drugs given together or 1 drug given by itself. Some common drugs include:
Carboplatin or cisplatin (both are available as generic drugs)
- Docetaxel (Taxotere)
- Gemcitabine (Gemzar)
- Nab-paclitaxel (Abraxane)
- Paclitaxel (Taxol)
- Pemetrexed (Alimta)
- Vinorelbine (Navelbine)
Chemotherapy may also damage healthy cells in the body, including blood cells, skin cells, and nerve cells. The side effects of chemotherapy depend on the person and the dose used, but they can include fatigue, low numbers of blood cells, risk of infection, mouth sores, nausea and vomiting, loss of appetite, diarrhoea, numbness and tingling in the hands and feet, and hair loss. Some lung cancer chemotherapy treatments do not cause significant hair loss.
Your medical oncologist can often prescribe drugs to help relieve many of these side effects. Hormone injections may be used to prevent white blood cell counts from becoming too low. Nausea and vomiting are also often avoidable. Learn more about preventing nausea and vomiting caused by cancer treatment. In many cases, side effects usually go away after treatment is finished.
Targeted therapy is a treatment that targets cancer’s specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. This type of treatment blocks the growth and spread of cancer cells and limits damage to healthy cells.
Not all tumours have the same targets. To find the most effective treatment, your doctor may run tests to identify the genes, proteins, and other factors in the tumour. For some lung cancers, abnormal proteins are found in unusually large amounts in the cancer cells. This helps doctors better match each patient with the most effective treatment whenever possible. In addition, research studies continue to find out more about specific molecular targets and new treatments directed at them.
Targeted therapy for NSCLC includes:
Epidermal growth factor receptor (EGFR) inhibitors. Researchers have found that drugs that block EGFR may be effective for stopping or slowing the growth of lung cancer when the cancer cells have EGFR mutations. This medication is a pill that can be taken by mouth. The side effects of EGFR inhibitors often include a rash that looks like acne and diarrhoea.
Osimertinib (Tagrisso) is a first treatment option for some people with NSCLC whose tumours have EGFR mutations. Osimertinib is also approved for the treatment of metastatic NSCLC with an EGFR mutation when other drugs listed above no longer work.
Erlotinib (Tarceva) has been shown to work better than chemotherapy if lung cancer has a mutation in the EGFRgene. It is an option for patients with locally advanced and metastatic NSCLC. This medication is a pill that can be taken by mouth. The side effects of erlotinib include a rash that looks like acne and diarrhoea.
Afatinib (Gilotrif) is an initial treatment option for NSCLC. It may also be an option for patients who have already received other treatments for squamous NSCLC. It is a type of drug called a tyrosine kinase inhibitor (TKI).
Dacomitinib (Vizimpro) is approved as an initial treatment for NSCLC that has an EGFR mutation. However, it is not frequently used.
Gefitinib (Iressa) is a first-generation EFGR inhibitor that is not widely used in the United States. It is more commonly used in Asia and some other parts of the world.
Anaplastic lymphoma kinase (ALK) inhibitors. ALK is a protein that is a part of the cell growth process. When present, this mutation helps cancer cells grow. ALK inhibitors help stop this process. Mutations in the ALK gene are found in about 5% of people with NSCLC. The following drugs are currently available to target this genetic change:
- Alectinib (Alecensa)
- Brigatinib (Alunbrig)
- Cretinib (Zykadia)
- Crizotinib (Xalkori)
- Lorlatinib (Lorbrena)
Drugs targeting ROS1 genetic changes.
Rare mutations to the ROS1 gene can cause problems with cell growth and cell differentiation, the process by which cells change from one type of cell into another. Drugs targeting changes to the ROS1 gene include:
- Crizotinib (Xalkori)
- Entrectinib (Rozlytrek)
Drugs targeting NTRK fusion. This type of genetic change is found in a range of cancers, including lung cancer, and causes cancer cell growth. Larotrectinib (Vitrakvi) is used to treat NTRK fusion for people with NSCLC.
Drugs targeting BRAF V600E mutations. The BRAF gene makes a protein that is involved in cell growth and can cause cancer cells to grow and spread. A BRAF V600E mutation can be targeted with a combination of dabrafenib (Tafinlar) and tremetinib (Mekinist).
Drugs targeting MET Exon 14 Skipping. MET Exon 14 Skipping is a genetic mutation found in over 3% of NSCLC. Capmatinib (Tabrecta) has been approved to target this genetic change.
Drugs targeting RET fusion. Up to 2% of all NSCLC cases are RET fusion-positive. Selpercatinib (LOXO-292) is approved to treat these genetic changes involving RET, which lead to uncontrolled cell growth.
Anti-angiogenesis therapy. Anti-angiogenesis therapy is focused on stopping angiogenesis, which is the process of making new blood vessels. Because a tumour needs the nutrients delivered by blood vessels to grow and spread, the goal of anti-angiogenesis therapies is to “starve” the tumour. The following anti-angiogenic drugs may be options for lung cancer:
Bevacizumab (Avastin, Mvasi) is an anti-angiogenic drug given along with chemotherapy for lung cancer. It may also be used along with chemotherapy and the immunotherapy drug atezolizumab (Tecentriq; see below) for metastatic NSCLC.
The risk of serious bleeding for patients taking bevacizumab is about 2%. However, it is more common for patients with squamous cell carcinoma, so bevacizumab is not recommended for patients with this type of NSCLC.
Ramucirumab (Cyramza) is approved for NSCLC along with the chemotherapy drug docetaxel.
Ramucirumab (Cyramza) is also approved in combination with the targeted therapy drug erlotinib as a first-line treatment of NSCLC for people with an EGFR mutation.
Treatment with targeted therapy for NSCLC is changing rapidly due to the pace of scientific research. New targeted therapies are being studied in clinical trials now. Talk with your doctor about additional options that may be available to you.
Side effects of targeted therapy depend on the drug(s) you’ve been prescribed. Talk with your doctor about possible side effects for a specific medication and how they can be managed.
Immunotherapy also called biologic therapy, is designed to boost the body’s natural defences to fight cancer. It uses materials made either by the body or in a laboratory to improve, target, or restore immune system function.
For example, the PD-1 pathway may be very important in the immune system’s ability to control cancer growth. Blocking this pathway with PD-1 and PD-L1 antibodies has stopped or slowed the growth of NSCLC for some patients. The following immunotherapy drugs block this pathway:
- Atezolizumab (Tecentriq)
- Durvalumab (Imfinzi)
- Nivolumab (Opdivo)
- Pembrolizumab (Keytruda)
Another immune pathway that may be targeted is the CTLA-4 pathway. In lung cancer, this pathway is often blocked in combination with a drug blocking the PD-1 pathway. The FDA has approved the combination of the anti-CTLA-4 antibody ipilimumab (Yervoy) and nivolumab as a first-line treatment for people with metastatic NSCLC who have levels of PD-L1 greater than or equal to 1%. This combination can also be used with chemotherapy for people with metastatic or recurrent NSCLC with no EGFR or ALK mutations.
For most people with advanced NSCLC that cannot be treated with targeted therapy (see above), immunotherapy or immunotherapy plus chemotherapy is often the preferred initial treatment.
Different types of immunotherapy can cause different side effects but, in general, severe side effects are less common than with chemotherapy. Common side effects include skin reactions, flu-like symptoms, diarrhoea, lung inflammation-causing shortness of breath, and weight changes. Talk with your doctor about possible side effects for the immunotherapy recommended for you.
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