Targeted therapies for lung cancer are drugs that target specific parts of lung cancer cells, such as proteins or genes, that help cancers grow and spread. Unlike standard chemotherapy, which destroys both lung cancer cells and healthy cells, targeted therapy only directly attacks cancer cells (but can have some side effects).
Targeted therapies mostly treat non-small-cell lung cancer (NSCLC), which accounts for about 85% of lung cancer cases.
“There are some indications that this could change in the near to middle term, with new types of therapies being developed for subtypes of small-cell lung cancer,” says radiation oncologist Mohamed E. Abazeed, MD, PhD, the co-leader of the Lung Cancer Program at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago, Illinois.
Researchers are investigating targeted therapies for small-cell lung cancer (SCLC), but current options are limited.
How Does Targeted Therapy Work for Lung Cancer?
Targeted therapies for lung cancer go after cancer-causing mutations and other alterations in the DNA of specific genes. These therapies essentially turn off those genes, which halts the growth of your lung cancer.
Targeted therapies for lung cancer are systemic treatments, like chemotherapy. That means they’re carried by your bloodstream to places all over your body, allowing them to reach wherever your lung cancer has spread. While lung cancer can spread anywhere in your body, the most common places are your:
- Liver
- Bones
- Brain
- Adrenal glands
There are a variety of targeted therapies approved to treat lung cancer, and they fight cancer in different ways, including by:
- Disrupting the chemical signals that instruct cancer cells to grow and divide
- Modifying certain proteins within cancer cells to kill those cells
- Cutting off cancer cells’ supply of oxygen and nutrients by blocking the development of new blood vessels
- Prompting your immune system to kill cancer cells
- Delivering toxins to cancer cells, killing them without damaging normal cells
In addition to fighting the cancer, targeted therapy also can help to relieve cancer symptoms while typically causing fewer side effects than chemotherapy. Fewer complications can improve your quality of life when you have advanced lung cancer.
When Is Targeted Therapy Recommended?
Targeted therapies for lung cancer go after specific targets, often referred to as biomarkers, such as gene mutations that drive the growth of lung cancer. An estimated 40% to 50% of patients with NSCLC have such biomarkers, making them eligible for targeted therapy.
“Ideally, we test all lung cancer patients soon after diagnosis to see if they would be a candidate for targeted treatments,” says medical oncologist Melissa Johnson, MD, the director of lung cancer research at the Sarah Cannon Research Institute in Nashville, Tennessee.
Targeted therapy may be recommended for you if:
- Your lung cancer has an identifiable biomarker, or target
- There is a medication available that specifically targets that biomarker
If you don’t have a biomarker that can be treated with targeted therapy, you will undergo a different treatment for your lung cancer, such as chemotherapy or immunotherapy. Your doctor also might combine chemotherapy with immunotherapy to treat your lung cancer.
Doctors typically use targeted therapy for later-stage lung cancer, in which the cancer has spread — or metastasized — to other parts of the body. They’re used on their own or in combination with chemotherapy. Research, however, has led to certain targeted therapies being used effectively in lung cancer’s earlier stages.
“In recent years, there are two drugs in particular — osimertinib for patients with EGFR mutations and alectinib for patients with ALK rearrangements — that have been tested for patients with early-stage lung cancers and approved to be used there with amazing results,” says Johnson.
“This represents an important shift: Targeted therapy is no longer limited to metastatic disease,” Abazeed says.
Your doctor also may recommend targeted therapy if:
- You have had surgery for lung cancer and your cancer has returned.
- You have undergone chemotherapy or other treatments and your cancer has returned or did not respond to those treatments.
- Your cancer has spread to your lymph nodes, which means surgery to remove it is not an option.
Biomarker Testing for Lung Cancer
Certain genes control how your cells work, including how they grow and divide. Changes to those genes — sometimes referred to as mutations or alterations — can derail that process and cause your cells to grow out of control. That’s how cancer develops.
Scientists have identified several genetic changes responsible for lung cancer, and they have developed drugs that specifically target those changes. But not everyone with lung cancer will have a genetic change for which a medication has been developed. To be a candidate for targeted therapy, your doctor will test you for certain biomarkers, which are specific molecules that indicate the presence of a cancer-causing genetic change.
Biomarker testing usually will require a biopsy. This is a procedure in which your doctor takes a small sample of tumor tissue for analysis in a lab. In some cases, however, your doctor may be able to use a type of blood test called a liquid biopsy to see if you have a biomarker.
If you have been diagnosed with lung cancer, it’s recommended that you undergo comprehensive biomarker testing, also referred to as next generation sequencing. Testing can identify many specific genetic mutations, alterations, and proteins in lung cancer-related genes. This can help to determine if your cancer can be treated with targeted therapy.
Biomarker testing also can help your doctor learn:
- How you are likely to respond to certain cancer treatments, including immunotherapy
- Whether you are a candidate for a clinical trial investigating potential lung cancer treatments
- To help predict whether your cancer may return after treatment. This can help to form a treatment plan but can’t tell your doctor whether you will benefit from that treatment.
There are 10 lung cancer-related genes for which treatments have been developed.
- EGFR is a protein found on the surface of cells that helps cells grow. Mutations in the EGFR gene cause the EGFR protein to boost cell growth, potentially leading to lung cancer. About 10% to 15% of lung cancers can be traced to these mutations, which occur mostly in nonsmokers and are more common in Asian populations.
- ALK is a gene that normally gets turned off before you are born. If it gets turned back on, it can partner, or fuse, with other genes to cause lung cancer. It accounts for about 4% of lung cancers, mostly in younger people and nonsmokers.
- ROS1 is a gene involved in many cancers, including some lung cancers. It can fuse with other genes, leading to uncontrolled cell growth and cancer. It accounts for about 1%-2% of lung cancers, mostly in younger people and nonsmokers.
- KRAS is a gene that helps to manage signals involved in cell growth. That signaling goes haywire if this gene develops a mutation called G12C, leading to uncontrolled cell growth and lung cancer. It accounts for about 25% of lung cancers, mostly in former and current smokers.
- BRAF is the name for a gene as well as for a protein that helps manage cell growth. When the BRAF gene develops a mutation, it alters the BRAF protein so that it sends faulty signals that lead to uncontrolled cell growth and lung cancer. About 4% of lung cancers are caused by BRAF mutations, but only one such mutation, called BRAF V600E, can be targeted by medication.
- MET is a gene that can become mutated and cause uncontrolled cell growth and lung cancer. This can happen in two ways: If you have extra copies of MET, called gene amplification, or, more commonly, a mutation that removes, or skips, a part of the MET gene called exon 14. Exon 14 skipping accounts for about 5% of lung cancers, while MET gene amplification is less common..
- RET is a gene that can fuse with another gene, called RET rearrangements, to cause uncontrolled cell growth and lung cancer. This accounts for about 1%-2% of lung cancers, mostly in younger people and nonsmokers. Less commonly, a RET mutation can lead to cancer-causing errors in your DNA.
- NTRK is a gene that can fuse with other genes, leading to uncontrolled cell growth and cancer. Though NTRK fusions account for fewer than 1% of all lung cancer, they can be treated effectively, so everyone with lung cancer should be tested.
- HER2 is a gene that can cause lung cancer if it becomes mutated or if you have too many copies of this gene, which is called gene amplification. Women and nonsmokers are more likely to have a HER2 mutation, which account for about 2% of lung cancer diagnoses.
- NRG1 is a gene that can develop errors that cause parts of a cell’s DNA to fuse together. When that happens, cells can begin to grow abnormally. This may cause lung cancer. Such fusions are rare, accounting for about 0.2% of lung cancers.
Researchers are learning more about the changes that drive cancer. This could lead to more and better targeted therapies in the future.
Types of Targeted Therapies for Lung Cancer
There are two broad classifications of targeted therapies for cancer: small molecule medicines and monoclonal antibodies.
Small molecule medicines are small enough to slip inside cancer cells and destroy them.
Monoclonal antibodies are too big to get into cells. Instead, they attack targets on the outside of cells or around them. Sometimes they're used to launch chemo and radiation straight into tumors. You usually get them through an IV in a vein in your arm at a hospital or clinic. Sometimes they're given as a shot.
The generic names of monoclonal antibodies end in "mab." Bevacizumab (Avastin) is a monoclonal antibody that works by blocking blood vessels that feed tumors.
Targeted therapies for lung cancer are generally put into the following three categories (based on mechanism or the process by which they work in your body):
- Kinase inhibitors block the processes by which cells grow and divide by going after a type of protein called a kinase. These typically come in pill form. They target many gene mutations in lung cancer. For example, ALK, EGFR, MET, NTRK, RET, and ROS1 genes all contain tyrosine kinases, which can be treated with targeted therapies.
- Antibody-drug conjugates (ADCs) use lab-made antibodies that bind to specific proteins on cancer cells to deliver chemotherapy drugs that damage or destroy those cells. They’re usually given in an IV.
- Angiogenesis inhibitors block the formation of new blood vessels, which tumors need in order to grow. They’re made from monoclonal antibodies and are given via an IV.
Targeted therapies for specific biomarkers in lung cancer
The following list describes treatments available for the 10 types of biomarkers for which targeted therapies have been developed and approved by the FDA.
- EFGR inhibitors. These drugs block the signals that the EFGR gene uses to tell cells to grow. It’s typically used in advanced lung cancer. There are many EFGR inhibitors available to treat a variety of EFGR gene mutations. Some of these drugs are used alone, while others may be used in combination with or after chemotherapy. Examples of EFGR inhibitors include afatinib (Gilotrif), dacomitinib (Vizimpro), erlotinib (Tarceva), and gefitinib (Iressa). Osimertinib (Tagrisso) is sometimes used after surgery for early-stage lung cancer.
- ALK inhibitors. These drugs block abnormal protein signals that cause cancer cells to grow and spread. This can happen if you have an ALK gene mutation called a rearrangement. Most of ALK inhibitors are given in advanced lung cancer. But one drug, called alectinib (Alecensa), is given in early-stage lung cancer after the tumor has been surgically removed. Other ALK inhibitors include brigatinib (Alunbrig), ceritinib (Zykadia), and ensartinib (Ensacove).
- ROS1 inhibitors. These drugs can shrink tumors in people with a ROS1 gene mutation called a rearrangement. They are used for advanced lung cancer. These drugs include ceritinib (Zykadia), crizotinib (Xalkori), entrectinib (Rozlytrek), lorlatinib (Lorbrena) repotrectinib (Augtyro), taletrectinib (Ibtrozi), and zidesamtinib (Jideytro).
- KRAS inhibitors. These drugs target a specific KRAS gene mutation called KRAS G12C, which then makes abnormal KRAS proteins that encourage cancer cells to grow and spread. KRAS inhibitors help prevent the growth of cancer cells. These drugs are used in advanced lung cancer and include adagrasib (Krazati) and sotorasib (Lumakras).
- BRAF inhibitors. These drugs are used if you have a mutation in your BRAF gene that causes changes to the BRAF protein, which helps lung cancer to grow. BRAF inhibitors are used in advanced lung cancer. You may take these drugs alone or, if you have the BRAF V600E mutation, in combination with a type of drug called a MEK inhibitor, which blocks the MEK protein, which is involved in cell growth. Examples of BRAF inhibitors include dabrafenib (Tafinlar), encorafenib (Braftovi), and vemurafenib (Zelboraf).
- MET inhibitors. These drugs treat a MET gene mutation called exon 14 skipping mutation, which causes the production of an abnormal MET protein that helps cancer cells grow and spread. Examples of these drugs include: capmatinib (Tabrecta), crizotinib (Xalkori), and tepotinib (Tepmetko). Telisotuzumab vedotin (Emrelis) is an ADC-targeted therapy used if your cancer is caused by having too many copies of the MET gene.
- RET inhibitors. These drugs treat an abnormal protein created when the RET gene becomes rearranged. This protein contributes to the growth of tumor cells. RET inhibitors include cabozantinib (Cometriq, Cabometyx), pralsetinib (Gavreto), and selpercatinib (Retevmo).
- Problems with the NTRK gene can cause it to make abnormal TRK proteins that fuel cell growth and cancer. These drugs shut down those proteins. They include entrectinib (Rozlytrek), larotrectinib (Vitrakyi), and repotrectinib (Augtyro).
- HER2-directed drugs. These drugs are used if you have specific changes in your HER2 gene that boost the growth of cancer cells. They include ado-trastuzumab emtansine (Kadcyla), sevabertinib (Hyrnuo), zenocutuzumab (Bizengri), and zongertinib (Hernexeos).
- Anti-angiogenic therapy (VEGF inhibitors). These drugs starve cancer cells by preventing the growth of new blood vessels that supply cancer cells with nutrients. They do this by disrupting a protein involved in blood vessel formation called vascular endothelial growth factor (VEGF). Examples include bevacizumab (Avastin) and ramucirumab (Cyramza).
- Antibody-drug conjugates (ADCs). These drugs use synthetic antibodies that go after specific proteins on cancer cells. Once they land on the cell, they deliver a dose of chemotherapy to kill the cancer. Drugs in this category include datopotamab deruxtecan (Datroway), fam-trastuzumab deruxtecan (Enhertu), and telisotuzumab vedotin (Emrelis).
What to Expect During Treatment
All lung cancer patients are unique, and doctors tailor each patient’s treatment to their specific needs. This includes the medications you take and how long you take them, as well as any follow-up care and testing to determine if your treatment is working.
While your treatment plan likely will be at least somewhat different from others with lung cancer, there are some things you can expect.
“We will typically monitor patients on targeted therapies every six weeks to three months with computed tomography (CT) scans and sometimes repeat next-generation sequencing (NGS) testing in the bloodstream,” says Johnson, who usually starts with frequent imaging tests before spacing them out at longer intervals.
For some patients, she also uses PET scans. “Sometimes I will alternate CT scan with PET scan to get an alternate look at the metabolic activity of a cancer, meaning where it is active within the body,” she explains.
The type of imaging test, she adds, is also determined by where your lung cancer has spread. PET scans are better able to monitor cancer in your bones, she says, while MRI helps to track lung cancer that’s spread to the brain.
But again, everything depends on the patient: “The way in which I follow patients varies and, honestly, evolves in reaction to the tumor’s behavior,” says Johnson.
Abazeed typically recommends CT scans every three to six months for patients with metastatic lung cancer, in which cancer has spread to other parts of the body. Blood tests also will be done to monitor the health of your other organs and track side effects of treatment.
“Ongoing surveillance is standard,” he says. “Overall, the goal is to ensure the therapy is controlling the cancer and to monitor for side effects.”
How is targeted therapy given?
Most targeted therapy comes in pill or capsule form, which you will take daily. But some of these therapies need to be given via IV infusion.
How long does targeted therapy last?
This depends in large part on the stage of your lung cancer. If you have metastatic lung cancer, you will take your targeted therapy for as long as it continues to work and you can tolerate its side effects.
“This may be months to several years,” says Abazeed.
It works differently for patients with earlier-stage lung cancer who receive targeted therapy after surgery.
“Targeted therapy is usually given for a defined period, often around three years in current practice for certain mutations,” says Abazeed.
Johnson points out that in general, targeted therapy will last longer than chemotherapy.
“Tolerance is better, and the therapies are potently inhibiting the cause, or molecular “driver” of the cancer, meaning the DNA mutation within the tumor. But the time on therapy does vary based on the specific therapy and the mutation.”
What Are the Side Effects of Targeted Therapy?
Each targeted therapy has a risk of side effects, and some side effects are unique to a particular targeted therapy. But targeted therapies for lung cancer do share some side effects. These include:
Your doctor can tell you what to expect based on the targeted therapy you take and its dose. Keep in mind that everyone’s experience is different. Some people have few side effects, while others have a lot. In general, they are less severe than chemotherapy side effects.
What Happens if Targeted Therapy Doesn’t Work?
Targeted therapy doesn't work if you don’t have a specific biomarker that matches with a targeted therapy drug. In such cases, your doctor may recommend other treatment options, such as chemotherapy, immunotherapy, or a clinical trial.
It’s also possible that your lung cancer will develop a resistance to the targeted therapy you take and become less and less effective. This can occur if something changes in the gene or protein being targeted or if your cancer cells begin to grow in new ways that don’t involve the target of your therapy.
“Some of the more recalcitrant cancers can develop resistance within six months of starting therapy, but other patients can remain on targeted therapy for years,” says Johnson.
If resistance does develop, your doctor can test your tumor to determine if another mutation is causing the resistance, says Abazeed. If so, another targeted therapy may help.
“In some cases, a second-generation or alternative targeted therapy can be used,” says Abazeed. “The landscape is evolving rapidly, and new options continue to emerge.”
But if no additional targeted therapy is available, your doctor will discuss other options with you, such as chemotherapy, immunotherapy, or a clinical trial, says Abazeed.
What Are the Benefits and Limitations of Targeted Therapy?
Targeted therapy has its shares of pros and cons.
Pros of targeted therapy include:
- Unlike chemotherapy, targeted therapy does less harm to healthy cells.
- Targeted therapy, in general, has fewer and less severe side effects than chemotherapy.
- Targeted therapy is often more effective than broader treatments like chemotherapy because of its ability to precisely target your cancer.
- Targeted therapy may improve survival rates.
- Targeted therapy can improve the effectiveness of other treatments, such as chemotherapy and immunotherapy, when they’re used together.
Cons of targeted therapy include:
- Targeted therapy does not work for all lung cancers, only those with specific biomarkers.
- Patients can develop resistance to targeted therapy over time, making it less and less effective.
- Targeted therapy drugs can be difficult to develop because of certain characteristics of the target, such as its structure or its function.
- Targeted therapies can be toxic, particularly when taken for longer periods, leading to potentially significant side effects.
- Targeted therapies are very expensive, which limits access to them for many if not most lung cancer patients.
What Are the Costs of Targeted Therapy?
Targeted therapy drugs are expensive. How much you pay out of pocket will depend on your insurance coverage. The prices of targeted therapy drugs do vary considerably. Costs range from just over $50 per pill to nearly $750 per pill. One estimate suggests that it costs $556,720 to treat one person with the EGFR inhibitor osimertinib.
Takeaways
Targeted therapy is highly effective at treating lung cancer, particularly advanced lung cancer that has spread to other parts of the body. However, it only works if your cancer results from specific gene mutations or abnormal proteins for which treatments have been developed. If you have been diagnosed with lung cancer, you should be tested to see if you would benefit from targeted therapy.
Targeted Therapy for Lung Cancer FAQs
Can targeted therapy cure stage IV lung cancer?
In general, targeted therapy does not cure stage IV lung cancer, but it can control the disease for prolonged periods. Some patients experience years of high-quality life with well-controlled cancer. Targeted therapy can cure earlier-stage lung cancer when combined with surgery and radiation.
Is targeted therapy more effective than chemotherapy?
It can be, because it precisely targets the source of your cancer. It also typically has fewer side effects than chemotherapy, making it better for quality of life.
What is the success rate of targeted therapy for lung cancer?
The success rate varies depending on the stage of your cancer, the drugs used to treat it, your overall health, and other factors. Overall, though, targeted therapies are effective at treating lung cancer. Over the 20 years or so since the first targeted therapy was developed, patients went from living just 8 to 10 months with advanced lung cancer to more than 50 months in some cases.
How long can you stay on targeted therapy?
You can remain on targeted therapy for as long it stays effective and you can tolerate the side effects.
