Targeted Therapy

Targeted therapy brochureTo help you understand and share this information, you can request our free booklet that summarizes the detailed information in the following sections. (This booklet was produced in May 2018, before the approval of several new targeted therapy drugs. Information about these drugs can be found in this section of the website.)

Targeted therapy is a type of treatment that uses drugs to attack cancer cells, including some kinds of lung cancer cells. As scientists have learned more about the driver mutationsA change to the DNA of cancerous cells that is considered to have been a cause of the development of the cancer and has helped the cancer cell to grow. Different from a passenger mutation in cells that cause cancer, they have been able to develop drugs that directly target some of these mutations. These drugs target specific parts of cells and the signals that proteins send to cells that cause them to grow and divide uncontrollably.

For more information about the driver mutations that can cause lung cancer and biomarker testingTesting for any unique changes to the DNA or other biomarkers found in a person’s cancer. The information is used to identify and create targeted therapies that are designed to work for a specific cancer tumor profile to determine the presence of driver mutations and help make lung cancer treatment decisions, go to Biomarker Testing.

Find out below about what targeted therapies are, what targeted therapy treatment options are available now, and whether targeted therapy might be a good treatment option for you.

What are targeted  therapies?

Targeted therapies may also be called:

  • Biomarker-driven therapies
  • Precision medicines
  • Molecularly targeted drugs or therapies

Targeted therapies are a type of treatment that targets specific molecules that are essential for cancer cells to grow and divide uncontrollably. They differ from standard chemotherapy in that they block the cancer cells' growth and division rather than, as chemotherapy does, kill the cancer cells directlly. Targeted therapies are more precise than chemotherapy drugs and do not affect healthy cells, which chemotherapy drugs do, so a patient is likely to experience fewer side effects with them.1,2

Kinase inhibitors

Kinases are specific proteins that act as enzymes to control cell functions, including cell signaling, growth, and division. There are different types of kinases. The proteins encoded by the ALK, EGFR, ROS1, and NTRK genes are all examples of a type of kinase called a tyrosine kinase. The BRAF gene encodes a different type of kinase, serine/threonine. If a gene has a driver mutation, the kinases can signal the cancer cell to grow and divide.

The five targeted therapy drugs and drug combination  that have been approved so far by the FDA for the treatment of specific driver mutations in lung cancer are all kinase inhibitors, which block the cell functions and keep the cancer from growing and spreading.

Genes with driver mutations in lung cancer for which there are FDA-approved kinase inhibitors on the market are:

  • ALK
  • EGFR sensitizing mutationsMutation in a gene that responds to tyrosine kinase inhibitors; also called non-resistant mutation, including exon 19 deletion and exon 21 (L858R) substitution mutations
  • ROS1
  • BRAF V600E
  • NTRK1

In addition, clinical trials are currently studying promising drugs to target these and other driver mutations.4

Side effects from treatment with targeted therapy kinase inhibitors are common, but just because a side effect is common does not mean that a patient will experience it. Before beginning treatment, the patient should discuss with the healthcare team what side effects might be expected and how to prevent or ease them. The patient should speak with the healthcare team if and when new side effects begin, as treating them early on is often more effective than trying to treat them once they have already become severe; in addition, it needs to be determined whether the side effects are related to treatment or not. What side effects are being experienced may impact future treatment plans. Although most side effects go away when treatment is over, some can last a long time.

Management techniques outlined below for common side effects of each targeted therapy are not all-inclusive; a patient's healthcare team will provide a more extensive set of possible side effects and what can be done for them.

ALK inhibitors

An anaplastic lymphoma kinase (ALK) rearrangement is a fusionA gene made by joining parts of two different genes between two genes: ALK and, most commonly, echinoderm microtubule-associated protein-like 4 (EML4)A gene that when combined with the anaplastic lymphoma kinase (ALK) gene produces an abnormal protein that leads to cancer cell growth. (In fact, the ALK gene rarely fuses to other genes.) The fusion of these two genes produces an abnormal ALK protein that causes cancer cells to grow and spread.

About 7% of patients with lung adenocarcinoma in the US have tumors with an ALK mutation. The fusion between ALK and EML4 is more common among younger patients (median age at diagnosis is 52 years), and nonsmokers or light smokers. It has rarely been found in patients with squamous cell lung cancer.5,6

Approved ALK INHIBITORS

There are currently five FDA-approved ALK targeted therapies, which are also known as anaplastic lymphoma kinase TKIS:

  • Alectinib (Alecensa®): Approved for patients with metastatic ALK-positive NSCLC, as detected by an FDA-approved test7
  • Brigatinib (Alunbrig®): Approved for patients with metastatic ALK-positive NSCLC who have progressed on or who are intolerant to crizotinib (Xalkori®)8
  • Ceritinib (Zykadia®)Approved for patients with metastatic ALK-positive NSCLC, as detected by an FDA-approved test9
  • Crizotinib (Xalkori®): Approved for patients with metastatic NSCLC, as detected by an FDA-approved test10
  • Lorlatinib (Lorbrena®): Approved for patients with metastatic ALK-positive NSCLC whose disease has progressed on crizotinib (Xalkori®) and at least one other ALK inhibitor for metastatic disease or whose disease has progressed on alectinib (Alecensa®) or ceritinb (Zykadia®) as first-line therapy for metastatic disease11

In addition, other ALK inhibitors are currently being studied in clinical trials.4

HOW are aLK inhibitors ADMINISTERED?

All five ALK inhibitors are given until disease progression or unacceptable toxicity.

  • Alectinib (Alecensa®) is given orally by capsule twice daily in a dosage of 600 mg, with food, until disease progression or unacceptable toxicity7
  • Brigatinib (Alunbrig®) is given orally by tablet once daily, with or without food. The dosage is 90 mg for the first 7 days. If 90 mg is tolerated during the first 7 days, the dosage is increased to 180 kg. Administered until disease progression or unacceptable toxicity8
  • Ceritinib (Zykadia®) is given orally by capsule once daily in a dosage of 750 mg, and must be taken at least 1 hour before a meal or at least 2 hours after a meal. Administered until disease progression or unacceptable toxicity9
  • Crizotinib (Xalkori®) is given orally by capsule twice daily in a dosage of 250 mg, with or without food, until disease progression or no longer tolerated10
  • Lorlatinib (Lorbrena®) is given orally by tablet once daily in a dosage of 100 mg, with or without food, until disease proression or unacceptable toxicity11

WHAT ARE THE SIDE EFFECTS OF THE ALK INHIBITORS?

The side effects of the ALK inhibitors differ by drug and by patient.7,8,9,10,11

Some common side effects of ALK inhibitors as a group include:

  • Nausea and vomiting: There are multiple medications available to prevent and treat nausea and vomiting. If one anti-nausea medication doesn't work, a different one or an additional one can be prescribed. Techniques such as distraction, relaxation, and positive imagery can help change the expectation and fear of nausea and vomiting12
  • Diarrhea: Avoidance of certain foods/beverages, such as prune juice, caffeine, dairy, and spicy foods. Eating frequent, small meals. Low-fiber foods. Water and other clear beverages to avoid dehydration13
  • Constipation:  More liquids. More fiber, or fiber supplements. Increased physical activity. Stool softeners or laxatives14
  • Fatigue: Treatment according to the underlying cause(s). If depression, for example, antidepressent medications may help. If anemia, possibly an infusion of red blood cells15,16

In addition, crizotinib (Xalkori®) has unique vision-specific side effects. These include:10

  • Trouble looking at light
  • Blurred vision
  • Double vision
  • Seeing flashes of light
  • New and increased floatersA bit of optical debris (as a dead cell or cell fragment) in the vitreous body or lens that may be perceived as a spot before the eye 

Before treatment, a patient's eyes can be examined by an eye doctor to establish a baseline; regular examinations after that can detect any changes that need to be treated. Over-the-counter drops to keep the eyes moist, good reading lights, wearing regular eyeglasses rather than contact lenses during treatment, and a warm washcloth over the eyes may also be helpful.17

Low testosterone is one source of fatigue in patients being treated with crizotinib (Xalkori®). This can also lead to sexual dysfunction and depression. Researchers have found that hormone replacement therapy is an effective method of managing these side effects.18

Some serious but rare side effects of ALK inhibitors as a group include:

  • Liver problems
  • Breathing problems (pneumonitisInflammation of the lungs that may be caused by disease, infection, radiation therapy, allergy, or irritation of lung tissue by inhaled substance)
  • Abnormal heartbeats

Some side effects can be relieved by reducing the dosage of ALK inhibitors.7,8,9.10,11

Get more tips on managing treatment-related side effects.

EGFR inhibitors

Epidermal growth factor receptor (EGFR) is a protein found in abnormally high levels on the surface of some cancer cells. Driver mutations involving EGFR can lead to uncontrolled cancer cell growth and survival.3

Approximately 15% of patients with lung adenocarcinoma in the US have tumors with an EGFR driver mutation. EGFR mutations are more often found in tumors of female nonsmokers.5,19

► Approved EGFR inhibitors

There are currently five FDA-approved EGFR targeted therapies, which are also known as epidermal growth factor receptor TKIs.

All of these are approved for first-line treatmentThe first treatment given for a disease. It is often part of a standard set of treatments, such as surgery followed by chemotherapy and radiation. When used by itself, first-line treatment is the one accepted as the best treatment. If it doesn't cure the disease or it causes severe side effects, other treatment may be added or used instead; erlotinib (Tarceva®) and osimertinib (Tagrisso®) are also approved for additional treatments:

  • Afatinib (Gilotrif®):20,21  Approved for first-line treatment of patients with metastatic NSCLC whose tumors have EGFR sensitizing (non-resistant) mutations, as detected by an FDA-approved test. (The most common of these are the exon 19 deletion and the exon 21 (L858R) substitution mutations. More rare sensitizing mutations are S768L, L861Q, and G719X.)
  • Dacomitinib (Vizimpro®):22 Approved for first-line treatment of patients with metastatic NSCLC whose tumors have EGFR exon 19 deletion or exon 21 (L858R) substitution mutations, as detected by an FDA-approved test
  • Erlotinib (Tarceva®):23 Approved for the treatment of patients with EGFR-positive metastatic NSCLC. This includes patients whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations, as detected by an FDA-approved test, who are receiving first-line or maintenance treatmentTreatment that is given to help keep cancer from coming back after it has disappeared following the initial therapy. It may include treatment with drugs, vaccines, or antibodies that kill cancer cells, and it may be given for a long time, or second- or subsequent-line treatment after progression following at least one prior chemotherapy regimen
  • Gefitinib (Iressa®):24Approved for the first-line treatment of patients with metastatic NSCLC whose tumors have EGFR exon 19 deletion or exon 21 (L858R) substitution mutations, as detected by an FDA-approved test
  • Osimertinib (Tagrisso®):25 Approved for first-line treatment of patients with metastatic NSCLC whose tumors have EGFR exon 19 deletion or exon 21 L858R substitution mutations, as detected by an FDA-approved test. It is also approved for second-line treatment of patients with metastatic NSCLC whose tumors are (EGFR) T790M-positive, as detected by an FDA-approved test, whose disease has progressed on or after EGFR TKI therapy

In addition, other EGFR inhibitors are currently being studied in clinical trials.

►How are EGFR inhibitors administered?

  • Afatinib (Gilotrif®) is given orally by table once daily in a dosage of 40 mg, 1 hour before or 2 hours after a meal, until disease progression or no longer tolerated20
  • Dacomitinib (Vizimpro®) is orally by tablet once daily in a dosage of 45 mg, with or without food, until disease progression or unacceptable toxicity22
  • Erlotinib (Tarceva®) is given orally by tablet once daily in a dosage of 150 mg, on an empty stomach (at least 1 hour before or 2 hours after the ingestion of food), until disease progression or unacceptable toxicity23
  • Gefinitb (Iressa®) is given orally by tablet once daily in a dosage of 250 mg, with or without food, until disease progression or unaccepable toxicity24
  • Osimertinib (Tagrisso®) is given orally by tablet once daily in a dosage of 80 mg, with or without food, until disease progression or unacceptable toxicity25

What are the side effects of EGFR inhibitors?

A very common side effect of EGFR inhibitors is an acne-like rash on the scalp, face, neck, chest, and upper back. This occurs because normal skin cells have a lot of EGFR, and they must grow quickly to maintain the skin’s surface layer. Drugs that target EGFR also turn off the signal for skin cells to grow normally, and make it harder for them to retain moisture. Depending on their severity, rashes may be treated with cortiocosteroids, as a cream or orally.20,22,23,24,25,26

Other common side effects of EGFR inhibitors as a group include:20,22,23,24,25

  • Itching (PruritusItching of the skin): skin creams with  menthol, topical steriods26
  • Diarrhea: Avoidance of certain foods/beverages, such as prune juice, caffeine, dairy, and spicy foods. Eating frequent, small meals. Low-fiber foods. Water and other clear beverages to avoid dehydration13
  • Mouth sores (StomatitisInflammation or irritation of the mucous membranes in the mouth): To lessen chances of  infection, eating a nutritious diet and maintaining a clean mouth and teeth27
  • Loss of appetite: Exercise before meals, 5 or 6 small meals a day, snacks, eating at times when feel hunger, addition of spices or anything else that makes foods more appealing,  nutritional supplements, appetite stimulants28

Serious but rare side effects that have been seen with one or more of the EGFR inhibitors are:20,22,23,24,25

  • Breathing problems because of interstitial lung diseaseA group of disorders that cause scarring of the lungs, which eventually affects patients' ability to get enough oxygen into their bloodstream and to breathe
  • Liver and kidney damage
  • Eye inflammation
  • Severe skin lesions
  • Bleeding problems
  • Heart issues

Some side effects can be relieved by reducing the dosage of EGFR inhibitors.20.22.23.24.25

Get more tips on managing treatment-related side effects..

ROS1 inhibitors

A ROS1 rearrangement is a fusion between two genes, ROS1 and another gene. As with ALK, the fusion of the two genes produces an abnormal protein that causes cancer cells to grow and spread.29

About 2% of patients with lung adenocarcinoma in the US have tumors with a ROS1 fusion. ROS1 fusions are more commonly found among younger patients (median age at diagnosis is 50 years), females, and never-smokers.5,30

Approved ROS1 inhibitors

There are currently two targeted therapies that has been approved for patients with metastatic NSCLC whose tumors are ROS1-positive:

  • Crizotinib (Xalkori®), a TKI that is also used for patients with ALK-positive tumors10
  • Entrectinib (RozlytrekTM), a TKI that is also used for patients with the NTRK1 mutation31

Other ROS1 inhibitors are currently being studied in clinical trials.4

How are ros1 inhibitors administered?

  • Crizotinib (Xalkori®) is given orally by capsule twice daily in a dosage of 250 mg, with or without food, until disease progression or no longer tolerated10
  • Entrectinib (RozlytrekTM) is given orally by capsule once daily in a dosage of 600 mg, with or without food, until disease progression or unacceptable toxicity31

What are the side effects of ROS1 inhibitors?

Several common side effects of ROS1 inhibitors are:10.31.32

  • Nausea and vomiting: There are multiple medications available to prevent and treat nausea and vomiting. If one anti-nausea medication doesn't work, a different one or an additional one can be prescribed. Techniques such as distraction, relaxation, and positive imagery can help change the expectation and fear of nausea and vomiting12
  • Diarrhea: Avoidance of certain foods/beverages, such as prune juice, caffeine, dairy, and spicy foods. Eating frequent, small meals. Low-fiber foods. Water and other clear beverages to avoid dehydration13
  • Constipation:  More liquids. More fiber, or fiber supplements. Increased physical activity. Stool softeners or laxatives14
  • Fatigue: Treatment according to the underlying cause(s). If depression, for example, antidepressent medications may help. If anemia, possibly infusion of red blood cells15,16

ROS1 inhibitor side effects also include vision-specific side effects. For one or both of the inhibitors, these may include, among others:10,31

  • Trouble looking at light
  • Blurred vision
  • Double vision
  • Seeing flashes of light
  • New and increased floatersA bit of optical debris (as a dead cell or cell fragment) in the vitreous body or lens that may be perceived as a spot before the eye 
  • Blindness
  • Retinal hemorrhaging
  • Cataracts

Before treatment, a patient's eyes can be examined by an eye doctor to establish a baseline; regular examinations after that can detect any changes that need to be treated. Over-the-counter drops to keep the eyes moist, good reading lights, wearing regular eyeglasses rather than contact lenses during treatment, and a warm washcloth over the eyes may also be helpful.17

Low testosterone is one source of fatigue in patients being treated with crizotinib (Xalkori®). This can also lead to sexual dysfunction and depression. Researchers have found that hormone replacement therapy is an effective method of managing these side effects.18

Both drugs may result in some serious but rare side effects.

Some side effects can be relieved by reducing the dosage of crizotinib (Xalkori®).10

Get more tips on managing treatment-related side effects.

BRAF V600E combination inhibitor

Mutations in the BRAF gene occur in about 1%-3% of lung adenocarcinoma patients. BRAF mutations are commonly seen in lung cancer patients who are current or former smokers. The V600E mutation is the most common mutation in the BRAF gene, but other mutations (called non-V600E mutations) can also occur.5,33

Approved BRAF combination inhibitor

There is currently one FDA-approved targeted treatment for patients with metastatic NSCLC with a BRAF V600E mutation as detected by an FDA-approved test. This is a combination treatment of a BRAF kinase inhibitor, dabrafenib (Tafinlar®), with a MEK kinase inhibitor, trametinib (Mekinist®).34,35

► HOW IS IT ADMINISTERED?

Dabrafenib (Tafinlar®) is given orally by capsule twice daily in a dosage of 150 mg approximately 12 hours apart and at least 1 hour before or at least 2 hours after eating. Trametinib (Mekinist®) is given orally as a tablet in a dosage of 2 mg, but just once daily, at least 1 hour before or at least 2 hours after eating.This combination is given until disease recurrence or unacceptable toxicity.34,35

WHAT ARE THE SIDE EFFECTS OF THE BRAF V600E combination INHIBITOR?

Some common side effects and management techniques of the BRAF V600E combination treatment include:34,35

  • Fatigue: Treatment according to the underlying cause(s). If depression, for example, antidepressent medications may help.  If anemia, possibly infusion of red blood cells15,16
  • Nausea and vomiting: There are multiple medications available to prevent and treat nausea and vomiting. If one anti-nausea medication doesn't work, a different one or an additional one can be prescribed. Techniques such as distraction, relaxation, and positive imagery can help change the expectation and fear of nausea and vomting12
  • Diarrhea: Avoidance of certain foods/beverages, such as prune juice, caffeine, dairy, and spicy foods. Eating frequent, small meals. Lower-fiber foods. Water and other clear beverages to avoid dehydration13
  • Dry skin: Avoidance of skin care products with fragrances. Skin products with  menthol or camphor. Topical steroids. Antihistamines26
  • Decreased appetite: Exercise before meals, 5 or 6 small meals a day, snacks, eating at times when feel hunger, addition of spices or anything else that makes foods more appealing,  nutritional supplements, appetite stimulants28

Some rare but serious side effects of the combination inhibitor include cutaneous squamous cell carcinomas. Patients on this combination of drugs should be followed by a dermatologist because of the risk of new skin cancers. Other rare but serious side effects include non-cutaneous malignancies, hemorrhagic events, and cardiomyopathydisease of the heart muscle that makes it harder for the heart to pump blood to the rest of the body. 34.35,36

Some side effects of these two drugs can be relieved by reducing their dosage.34,35

Get more tips on managing treatment-related side effects.

NTRK inhibitors

About 3% of lung adenocarcinoma patients have an NTRK1 gene fusion. NTRK1 fusions are more likely to be seen in patients who are light or never-smokers.5,32

Approved NTRK inhibitors

There are currently two FDA-approved targeted therapy TKIs, larotrectinib (Vitrakvi®) and entrectinib (RozlytrekTM) that are approved for the treatment of patients with solid tumors (e.g., lung, thyroid, colon) whose tumors:31,37

  • have an NTRK gene fusion (including the NTRK1 gene fusion among lung adenocarcinoma patients) without a known acquired resistance mutation,
  • are metastatic or where surgical resection is likely to result in severe morbidity, and
  • have no satisfactory alternative treatments or have progressed following treatment.

Larotrectinib (Vitrakvi®) was the first targeted therapy FDA-approved for cancer patients regardless of the type of solid tumor (e.g., lung, thyroid, colon) at the time is was initially approved. Both larotrectinib (Vitrakvi®) and entrectinib (RozlytrekTM) are sometimes referred to as a tissue-agnostic or tumor-agnostic treatments.

HOW is it administered?

  • Larotrectinib (Vitrakvi®) is given to adults orally as a capsule twice daily in a dosage of 100 mg, with or without food, until disease progression or unacceptable toxicity.37
  • Entrectinib (RozlytrekTM) is given to adults  orally as a capsule once daily, with or without food, until disease progression or unaccptable toxicity.31

what are the side effects of ntrk inhibitors?

Some common side effects of NTRK inhibitors include:31,37

  • Fatigue: Treatment according to the underlying cause(s). If depression, for example, antidepressent medications may help.  If anemia, possibly infusion of red blood cells.15,16
  • Nausea and vomiting: There are multiple medications available to prevent and treat nausea and vomiting. If one anti-nausea medication doesn't work, a different one or an additional one can be prescribed. Techniques such as distraction, relaxation, and positive imagery can help change the expectation and fear of nausea and vomiting12
  • Dizziness: Anti-emetic drugs prescribed for nausea and vomiting, drinking plenty of fluids, and changing position and moving around slowly and carefully38
  • Constipation: More liquids. More fiber, or fiber supplements. Increased physical activity. Stool softeners or laxatives14
  • Diarrhea: Avoidance of certain foods/beverages, such as prune juice, caffeine, dairy, and spicy foods. Eating frequent, small meals. Low-fiber foods. Water and other clear beverages to avoid dehydration13

Some side effects can be relieved by reducing the dosage of larotrectinib (Vitrakvi®).37

Get more tips on managing treatment-related side effects.

Which driver mutations identified in lung cancer are being studied in clinical trials?

Currently clinical trials are open for many drugs that inhibit the effect of mutations seen in NSCLC and SCLC. The targeted treatments are being studied alone, as well as in combination with other targeted agents, immunotherapy, chemotherapy, and radiation therapy. As the number of known driver mutations in lung cancer tumors increases, so does the number of drugs being developed to target them. Patients should discuss with their healthcare team whether participating in a clinical trial might be a good option Drugs that are currently being studied are intended to act against the following driver mutations:46

Driver Mutation Lung Adenocarcinoma Squamous Cell Lung Cancer Small Cell Lung Cancer
TP53 X X X
EGFR X    
KRAS X    
MEK1 (MAP2K1) X X  
RB1 X X X
ALK (fusion) X    
MYC X Rare X
FGFR1 (amp) X X X
RET X    
MET      
    Amplification (de novo) X    
    Amplification (EGFR TKI-resistant) X    
    Exon 14 skipping X X  
PTEN X X X
PIK3CA      
    Mutation X X  
    Amplification X X X
BRAF X    
ROS1 X    
NTRK1 X    
HER2      
    Mutation X    
    Amplification X    
IGR1     X
PARP1   X X
Notch signaling     X

Resistance to tyrosine kinase inhibitors (TKIs)

The biggest challenge of TKIs is that a majority of patients with lung cancer who initially benefit from them eventually develop resistance. Acquired resistanceDisease progression after a complete or partial response to treatment after treatment with a targeted therapy can be defined as disease progression in a patient after initial benefit from a TKI.47

Cancer cells are clever enough to bypass roadblocks to their survival and often further mutate to overcome the effects of targeted therapies. For example, the most common way lung adenocarcinomas become resistant to EGFR inhibitors is by mutating to a drug-resistant state that stops the drugs from working. Another way a tumor can become resistant to EGFR inhibitors is by activating a different signaling pathwayDescribes a group of molecules in a cell that work together to control one or more cell functions, such as cell division or cell death. After the first molecule in a pathway receives a signal, it activates another molecule. This process is repeated until the last molecule is activated and the cell function is carried out. Abnormal activation of signaling pathways can lead to cancer, and drugs are being developed to block these pathways. These drugs may help block cancer cell growth and kill cancer cells in the cell to bypass the pathway that the drug uses to kill the cells. In a small number of cases, the lung adenocarcinoma may transform into small cell lung cancer.47,48,49

Similarly, lung cancers with an ALK or ROS1 rearrangement normally have good responses to ALK or ROS1 inhibitors. However, the majority of patients also eventually become resistant to the effects of the drugs. In many cases, resistance arises because of further mutations.48,50

Doctors and scientists are working to overcome resistance in tumors and to keep the TKIs effective against cancer for longer periods of time. Their approaches include:48

  • Simultaneously prescribing multiple inhibitors, in case a different mutation in the cell has been activated
  • Developing the next generation of inhibitors that will inhibit not only the activity of the mutated gene but also the mutant form it could change into

If a patient’s cancer has grown after treatment with a TKI, a decision needs to be made about the next treatment option. A patient's doctor may recommend that a biopsy be done of one of the tumors that is growing to determine whether there is a new mutation. For example, for EGFR patients, if the (EGFR) T790M mutation is present (it is found in about 50%-60% of patients who have this biopsy), the doctor may recommend the next-generation EGFR inhibitor, osimertinib (Tagrisso®) or a clinical trial.51,52

In addition to osimertinib (Tagrisso®) for EGFR patients, several other next-generation inhibitors have already been approved, including ceritinib (Zykadia®), alectinib (Alecensa®), and brigatinib (Alunbrig®) for ALK-positive NSCLC patients. Scientists are researching approaches to overcome resistance to crizotinib (Xalkori®) in ROS1-positive lung cancer and learning about acquired resistance in BRAF-positive lung cancers.

Finding a clinical trial that might be right for you

If you are considering participating in a clinical trial, start by asking your healthcare team whether there is one that might be a good match for you in your geographic area. In addition, there are several resources to help you find one that may be a good match.

Resources to help you navigate your clinical trials search:

  • LUNGevity Clinical Trial Finder: https://clinicaltrials.lungevity.org
    • Find available clinical trials by type of lung cancer and geographic location
    • Also find information and links to the medical centers at which these clinical trials are taking place
  • EmergingMed: www.emergingmed.com/lcctal/home
    • LUNGevity partners with this free clinical trials matching service to help you with the decision of whether to participate in a clinical trial.
    • EmergingMed helps you identify lung cancer clinical trials for which you may be eligible
    • Clinical trial navigators are available Monday through Friday from 9:00am to 5:00pm ET at 877-769-4834
  • National Cancer Institute (NCI)www.cancer.gov/clinicaltrials/search
  • My Cancer Genomewww.mycancergenome.org
    • My Cancer Genome gives up-to-date information on what mutations make cancers grow and related treatment options, including available clinical trials
  • Lung Cancer Mutation Consortium (LCMC):   www.golcmc.com
    • Composed of 16 leading cancer centers across the country
    • LCMC’s goal is to examine the tumors of patients who have advanced (stage IIIB or IV) non-small cell lung cancer adenocarcinoma, and match those patients to the best possible therapies, including clinical trials
  • Lung Cancer Master Protocol (Lung-MAP)www.lung-map.org
    • For patients with advanced non-small cell lung cancer
    • LUNG-MAP is a collaboration of many research sites across the country. They use a unique approach to match patients to one of several drugs being developed

In addition, if you are interested in a specific drug or other treatment that is being developed, you can often find information about studies for that drug on the website of the company developing it.

Learn more about clinical trials here.


Questions to ask your healthcare team about targeted therapy

Print this list

  1. Why do you recommend a targeted cancer therapy for me?
  2. What mutation do I have?
  3. What kind of targeted cancer therapy will I get?
  4. Will targeted cancer therapy be my only treatment or will it be combined with another treatment?
  5. How often will I take this therapy and for how long?
  6. How and when will I know if the treatment is working?
  7. How often do I need to be seen between treatments for a physical exam and/or lab work?
  8. Can I expect to see changes in my lab results while on this treatment?
  9. Are there any tests or procedures I will need during the treatment?
  10. What side effects can I expect?
  11. What can I do to manage these side effects?
  12. How will this treatment affect my daily life? Will I be able to work, exercise, and perform my usual activities?
  13. What tests will I need after treatment is completed?
  14. Are there any long-term health issues I should expect from treatment with targeted therapy?
  15. How much will my treatment cost?

Updated August 29 2019


References

  1. Abramson RG. Overview of Targeted Therapies for Cancer. My Cancer Genome website. http://www.mycancergenome.org/content/other/molecular-medicine/overview-of-targeted-therapies-for-cancer. Updated May 27, 2019. Accessed July 24, 2019. 
  2. Targeted Cancer Therapies. National Cancer Institute website. https://www.cancer.gov/about-cancer/treatment/types/targeted-therapies/targeted-therapies-fact-sheet. Updated June 25, 2019. Accessed July 24, 2019.
  3. NCI Dictionary of Cancer Terms. National Cancer Institute website. https://www.cancer.gov/publications/dictionaries/cancer-terms. Acccessed July 24, 2019.
  4. ClinicalTrials.gov. US National Institutes of Health website. https.clinicaltrials.gov. Accessed July 24, 2019.
  5. Hirsch FR, Suda K, Wiens J, Bunn PA, Jr. New and emerging targeted treatments in advanced non-small cell lung cancer. Lancet. Sep 3 2016; 388(10048): 1012-1024. Accessed July 24, 2019.
  6. Shaw AT, Solomon B. Anaplastic lymphoma kinase (ALK) fusion oncogene positive non-small cell lung cancer. Uptodate website. https://www.uptodate.com/contents/anaplastic-lymphoma-kinase-alk-fusion-oncogene-positive-non-small-cell-lung-cancer. Updated Jun 21, 2019. Accessed July 24, 2019.
  7. Alecensa® (alectinib) capsules [package insert]. Genentech, Inc. South San Francisco, CA. http://www.gene.com/download/pdf/alecensa_prescribing.pdf. Revised June 2018. Accessed July 24, 2019.
  8. Alunbrig® (brigatinib) tablets [package insert]. ARIAD Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceuticals Company. Cambridge, MA. http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208772lbl.pdf. Revised April 2017. Accessed July 24, 2019.
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