Targeted therapy is a type of treatment that uses drugs to attack cancer cells, including some kinds of lung cancer cells.
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As scientists have learned more about the A 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 Testing 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 is targeted therapy?
Targeted therapies may also be called:
- Biomarker-driven therapies
- Precision medicines
- Molecularly targeted drugs or therapies
Targeted therapy is a type of cancer treatment that identifies and attacks specific parts of cancer cells and the signals that proteins send to cancer cells that cause them to grow and divide uncontrollably.1 Targeted therapies are precise; they prevent the growth and spread of the cancer cells only. They do no harm to the body's normal, healthy cells.
Because each targeted therapy works to control a specific driver mutation, a patient may be treated with that targeted therapy only if they have the driver mutation for which the targeted therapy is intended.
Targeted therapies are approved primarily for patients whose lung cancer is Characterized by metastasis, which is the spread of cancer from the primary site, or place where it started, to other places in the body; that is, the cancer has spread from its original site to other places in the body.
Targeted therapies work differently from the other three types of lung cancer drug treatments. To summarize the differences:1
- Targeted therapy: Blocks the cancer cells' growth and division; leaves healthy cells alone
- Standard chemotherapy: Attacks the cancer cells directly, but also attacks healthy cells
- Immunotherapy: Stimulates the body's immune system to attack the cancer cells
- Angiogenesis inhibitor: Stops the formation of new blood vessels to cut off the tumor's blood supply
In addition, except for one medication given intravenously (an infusion through a vein), targeted therapies are administered orally (typically by pill once or twice daily). Other drug treatments (such as chemotherapy and immunotherapy) are most likely to be administered intravenously.
A targeted therapy is given to a patient until The continuation in the growth or spread of cancer—the lung cancer continues to grow and spread—or the side effects of the drug become intolerable.
Types of targeted therapies
Kinases are specific proteins that act as Special proteins that the body produces to control its cells and carry out chemical reactions quickly to control cell functions, including The procss by which a cell responds to substances outside the the cell, growth, and division. There are different types of kinases. The proteins encoded by the ALK, EGFR, MET, NTRK, RET, and ROS1 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.1
The targeted therapy drugs that have been approved so far by the FDA for the treatment of driver mutations in lung cancer are all kinase inhibitors, which block the cell functions and keep the cancer from growing and dividing. Except for the BRAF V600E combination treatment, all of the inhibitors are tyrosine kinase inhibitors (TKIs). Kinase inhibitors are all administered orally.
An antigen is any substance that causes the body to have an immune response against it. Cancer cells have antigens on them that can cause an immune response by antibodies, which are specific to the antigen. While in nature an antibody can only bind to one antigen, bispecific antibodies developed by researchers are able to target two antigens and block signaling functions that allow cancer cells to flourish.1 One such bispecific antibody has been developed for a specific variation of the EGFR gene. This drug is given as an infusion through the vein.
RAS GTPase family inhibitors
In normal cells, the KRAS protein acts like an on/off switch to control signaling pathways that manage cell growth. The KRAS gene controls the production of the KRAS protein. A mutation in the KRAS gene leads to the production of a faulty protein that is always on, or active, resulting in the continuous, out-of-control proliferation of cells and leading to the formation of cancerous tumors. Different KRAS mutations are found in lung cancer. All these mutations lead to an “on” KRAS protein. One inhibitor has been developed to target the most common mutation of the KRAS gene in NSCLC. This drug, a RAS GTPase family inhibitor, is administered orally.44
Where do targeted therapies fit into a treatment plan?
Sometimes, treatment with a targeted therapy will be the only treatment a patient receives. However, a targeted therapy may also be used before, together with, or after other treatments; treatment will depend on when the driver mutation was discovered, the patient's response to treatment, and other individual factors that the doctors consider. The other treatments are most likely to include another targeted therapy, chemotherapy, chemotherapy-immunotherapy, an angiogenesis inhibitor, and/or radiation therapy. In addition, in those cases where a targeted therapy is appropriate and there is more than one approved therapy for a particular driver mutation, doctors again consider factors specific to the patient before prescribing a particular treatment.2
Driver mutations with FDA-approved targeted therapies
Genes with driver mutations for which there are FDA-approved targeted therapies for the treatment of lung cancer are:
- BRAF V600E
- EGFR (including mutations not sensitive to TKIs)
- MET exon 14 skipping
All current FDA-approved targeted therapies treat non-small cell lung cancer (NSCLC). There are as yet no approved targeted therapies for small cell lung cancer.
Clinical trials are currently studying promising drugs to target these and other driver mutations; read more about them later in this section.
An anaplastic lymphoma kinase (ALK) rearrangement is a A gene made by joining parts of two different genes between two genes: ALK and, most commonly, echinoderm microtubule-associated protein-like 4 (EML4). (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 5% of patients with NSCLC in Western populations have tumors with an ALK fusion. The fusion between ALK and EML4 is more common among younger patients (median age at diagnosis is 52 years); nonsmokers or light smokers; and those with lung adenocarcinoma. It has rarely been found in patients with squamous cell lung cancer.3
What are the Approved ALK TKIs?
There are currently five FDA-approved ALK TKIs:
- Alectinib (Alecensa®):4 Approved for patients with metastatic ALK-positive NSCLC, as detected by an FDA-approved test
- Brigatinib (Alunbrig®):5 Approved for adult patients with metastatic ALK-positive NSCLC, as detected by an FDA-approved test
- Ceritinib (Zykadia®):6 Approved for patients with metastatic ALK-positive NSCLC, as detected by an FDA-approved test
- Crizotinib (Xalkori®):7 Approved for patients with metastatic ALK-positive NSCLC, as detected by an FDA-approved test
- Lorlatinib (Lorbrena®):8Approved for adult patients with metastatic ALK-positive NSCLC, as detected by an FDA-approved test
WHAT ARE THE SIDE EFFECTS OF THE ALK TKIs?
Some common side effects of ALK TKIs as a group include:
- Swelling of the hands or feet
- Liver problems
- Inflammation of the lungs that may be caused by disease, infection, radiation therapy, allergy, or irritation of lung tissue by inhaled substance
- Abnormal heartbeats
In addition, crizotinib (Xalkori®) has unique vision-specific side effects. These include:7
- Trouble looking at light
- Blurred vision
- Double vision
- Seeing flashes of light
- New or increased A 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
Low testosterone is one source of fatigue in patients being treated with crizotinib (Xalkori®). This can also lead to sexual dysfunction and depression.9
Mutations in the BRAF V600E gene occur in 1%-3% of lung adenocarcinoma patients. Most of these patients are current or former smokers.10
What is the APPROVED BRAF V600E 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®).11
WHAT ARE THE SIDE EFFECTS OF THE BRAF V600E COMBINATION INHIBITOR?
Side effects of the BRAF V600E combination inhibitor vary by patient.11
Some common side effects of the BRAF V600E combination inhibitor include:
- Dry skin
- Decreased appetite
- Swelling of the hands or feet
- Difficulty breathing
Among the more serious but less common side effects of the BRAF V600E combination inhibitor are:11
- Vision toxicities
- A disease of the heart muscle that makes it more difficult for the heart to pump blood to the rest of the body
- A higher-than-normal amount of glucose in the blood
Approximately 15% of patients with NSCLC in the US and 35% of patients from East Asia have tumors with an EGFR (epidermal growth factor receptor) driver mutation. Regardless of the patient's ethnicity, EGFR driver mutations are more often found in tumors of females and nonsmokers. Most commonly, these patients have lung adenocarcinoma.12,13
What are the approved EGFR drugs?
There are currently six FDA-approved EGFR TKIs. All except mobercertinib (ExkivityTM), which is approved for EGFR exon 20 insertion mutations, are approved for EGFR exon 19 deletion and exon 21 (L858R) substitution mutations. Afatinib (Gilotrif®) and osimertinib (Tagrisso®) have additional indications as well:
- Afatinib (Gilotrif®):14 Approved for The first therapy given for a disesase of patients with metastatic NSCLC whose tumors have EGFR 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. The rarer mutations are S768L, L861Q, and G719X.)
- Dacomitinib (Vizimpro®):15 Approved for first-line treatment of patients with metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations, as detected by an FDA-approved test
- Erlotinib (Tarceva®):16,17 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 Treatment 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. Erlotinib (Tarceva®) is also approved in combination with ramucirumab (Cyramza®), an angiogenesis inhibitor, for the first-line treatment of metastatic NSCLC with EGFR exon 19 deletions or exon 21 (L858R) substitution mutations
- Gefitinib (Iressa®):18 Approved for the first-line treatment of patients with metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations, as detected by an FDA-approved test
- Mobercertinib (ExkivityTM):45 Approved for the treatment of adult patients with locally advanced or metastatic EGFR exon 20 insertion-mutant NSCLC, as detected by an FDA-approved test, and who have received prior platinum-based chemotherapy
- Osimertinib (Tagrisso®):19Approved for first-line treatment of patients with metastatic NSCLC whose tumors have EGFR exon 19 deletions 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, and whose disease has progressed on or after EGFR TKI therapy.
Note: The US FDA granted approval for the use of osimertinib (Tagrisso®) as The additional cancer treatment given after the primary treatment to lower the risk that the cancer will come back after surgical removal of a tumor in adult patients with The extent of a cancer in the body 1B to IIIA NSCLC whose tumors are mostly nonsquamous and have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations, as detected by an FDA-approved test.20
There currently is also one FDA-approved treatment that is not a TKI for the treatment of exon 20 insertion mutations: this treatment is an EGFR bispecific antibody.40
- Amivantamab-vmjw (RybrevantTM):41 Approved for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy
What are the side effects of EGFR Drugs?
Some common side effects of EGFR drugs as a group include:
- Mouth sores
- Loss of appetite
- Inflammation around nails
- A group of disorders that cause scarring of the lungs, which eventually affects the body's ability to get enough oxygen into the bloodstream and to breathe
- Vision toxicities
- Severe skin lesions
Approximately 30% of patients with NSCLC in the US have tumors with KRAS (Kirsten Rat Sarcoma) driver mutation. KRAS mutations are most often found in tumors of smokers. Most commonly, these patients have lung adenocarcinoma.42
What is the approved KRAS inhibitor?
There is currently one FDA-approved inhibitor, specifically for the KRAS G12C mutation. This mutation accounts for approximately 13% of NSCLC cases.44
- Sotorasib (Lumakras™):43 Approved for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy.
What are the side effects of the KRAS inhibitor?
Side effects of the KRAS inhibitor vary by patient.
Some common side effects of KRAS inhibitor include:43
- Musculoskeletal pain
- Liver issues
Among the more serious but less common side effects of the KRAS inhibitors is interstitial lung disease.43
Approximately 3%-4% of NSCLC patients have a mutation that leads to MET (mesenchymal-epithelial transition) exon 14 skipping. Patients with MET-positive lung cancers are most likely to have a smoking history; a minority are never-smokers.21,22
What are the APPROVED MET TKIs?
There are currently two FDA-approved MET TKIs:
- Capmatinib (TabrectaTM):23 Approved for the treatment of adult patients with metastatic NSCLC whose tumors have a mutation that leads to MET exon 14 skipping, as detected by an FDA-approved test
- Tepotinib (Tepmetko®):24 Approved for the treatment of adult patients with metastatic NSCLC whose tumors have a mutation that leads to MET exon 14 skipping
WHAT ARE THE SIDE EFFECTS OF THE MET TKIs?
Some common side effects of the MET TKIs as a group include:
- Swelling of the hands or feet
- Fatigue and weakness
- Musculoskeletal pain
- Shortness of breath
- Loss of appetite
- Liver damage
What are the approved NTRK TKIs?
There are currently two FDA-approved NTRK TKIs:
- Entrectinib (Rozlytrek®):27 Approved for the treatment of adult and pediatric patients 12 years of age and older with An abnormal mass of tissue that usually does not contain cysts or liquid areas. Solid tumors may be benign or malignant that:
- have an NTRK gene fusion with a known Disease progression after a complete or partial response to treatment, or disease progression after six months or more of stable disease, after treatment with a targeted therapy mutation,
- are metastatic or where surgical resection is likely to result in severe Medical problems caused by a treatment, and
- have progressed following treatment or have no satisfactory alternative treatment
- Larotrectinib (Vitrakvi®):28 Approved for the treatment of patients with NTRK solid tumors that:
- have an NTRK gene fusion without a known acquired resistance mutation
- are metastatic or where surgical resection is likely to result in severe morbidity, and
- have progressed following treatment or have no satisfactory alternative therapy
what are the side effects of ntrk TKIs?
Some common side effects of NTRK inhibitors as a group include:
High AST (aspartate aminotransferase) levels, indicating liver issues
High ALT (alanine aminotransferase) levels, indicating liver issues
- Congestive heart failure
- Skeletal fractures
- Central nervous system effects
- Vision disorders
What are the approved RET TKIs?
There are currently two FDA-approved RET TKIs:
- Selpercatinib (RetevmoTM):31 Approved for the treatment of adult patients with metastatic RET fusion-positive NSCLC, as detected by an FDA-approved test
- Pralsetinib (GavretoTM):32 Approved for the treatment of adult patients with metastatic RET fusion-positive NSCLC
WHAT ARE THE SIDE EFFECTS OF THE RET TKIs?
Some common side effects of RET TKIs as a group include:
- High blood pressure
- Dry mouth
- Musculoskeletal pain
- Swelling of the hands or feet
- High AST, indicating liver issues
- High ALT, indicating liver issues
- Other laboratory test abnormalities (eg., increased glucose and decreased calcium)
A ROS1 (receptor tyrosine kinase) 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.
About 1%-2% of patients with NSCLC in the US and 2%-3% in East Asia have tumors with a ROS1 mutation. ROS1 tumors are more commonly found among younger patients (median age at diagnosis is 50 years), females, never-smokers, and patients with lung adenocarcinoma.12,33
What are the APPROVED ROS1 TKIs?
There are currently two FDA-approved ROS1 TKIs:
- Crizotinib (Xalkori®):7 Approved for patients with metastatic NSCLC whose tumors are ROS1-positive, as detected by an FDA-approved test
- Entrectinib (Rozlytrek®):8 Approved for adult patients with metastatic NSCLC whose tumors are ROS1-positive
WHAT ARE THE SIDE EFFECTS OF ROS1 TKIs?
Some common side effects of ROS1 TKIs as a group include:
- Muscle aches
Among the more serious but less common side effects of the ROS1 TKIs as a group are:
- Vision disorders
- Low testosterone
- Skeletal fractures
- Central nervous system effects
Crizotinib (Xalkori®) is also approved for the treatment of metastatic ALK-positive NSCLC; see the earlier section about ALK TKIs for more detail on the rarer eye and testosterone side effects of this drug.
Management of targeted therapy side effects
As seen above, targeted therapies can cause side effects. However, just because a side effect is possible does not mean that a patient will experience it. Before beginning treatment with a targeted therapy, the patient should discuss with the healthcare team what side effects, both common and rare, 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.
Resistance to tyrosine kinase inhibitors (TKIs)
The biggest challenge of TKI targeted therapies is that a majority of patients with lung cancer who initially benefit from them eventually develop resistance. Acquired resistance can be defined as disease progression in a patient after initial benefit from a TKI.34
Cancer cells are adept enough to bypass roadblocks to their survival and often further mutate to overcome the effects of TKIs. Another way a tumor can become resistant to TKIs is by activating a different signaling pathway in the cell to bypass the pathway that the TKI uses to kill the cells. In a small number of cases among EGFR patients, the lung adenocarcinoma may even transform into other histologies, such as SCLC. 34,35,36
- Simultaneously prescribing multiple TKIs, 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
- Prescribing other combination treatments (e.g., a TKI in combination with chemotherapy, immunotherapy, or radiation therapy)
In the meantime, if a patient's cancer has progressed 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 on one of the tumors that is growing to determine whether there is a new mutation, but will consider all of the treatment options mentioned earlier and make a determination based on the patient's particular situation.
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 do the number of drugs being developed to target them. Patients should discuss with their doctors whether participating in a clinical trial might be a good option Read more about resources to help locate clinical trials later in this section.
Targeted therapies drugs that are currently being studied are intended to act against the following driver mutations:39
|Driver Mutation||Lung Adenocarcinoma||Squamous Cell Lung Cancer||Small Cell Lung Cancer|
|Amplification (de novo)||X|
|Amplification (EGFR TKI-resistant)||X|
|Exon 14 skipping||X||X|
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.
People are often surprised that a clinical trial is not the last option one turns to when standard treatments have failed. Today, clinical trials may present the FIRST line of treatment.
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 Genome: www.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 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.
Updated September 16, 2021
- NCI Dictionary of Cancer Terms. National Cancer Institute website. https://www.cancer.gov/publications/dictionaries/cancer-terms. Accessed April 15, 2021.
- NCCN Clinical Practices Guidelines in Oncology: Non-Small Cell Lung Cancer (NSCLC). Version 8.2020. https://www.nccn.org/professionals/physician_gls/pdf/nsclc.pdf. Posted Stepember 15, 2020. Accessed November 16, 2020.
- Solomon B, Lovly C. Anaplastic lymphoma kinase (ALK) fusion oncogene positive non-small cell lung cancer. In: Lilenbaum RC. ed., Uptodate. Waltham, MA: UpToDate, Inc.: 2021. https://www.uptodate.com/contents/anaplastic-lymphoma-kinase-alk-fusion-oncogene-positive-non-small-cell-lung-cancer/print. Updated February 10, 2021. Accessed February 18, 2021.
- Alecensa® (alectinib) capsules [package insert]. Genentech, Inc. South San Francisco, CA. http://www.gene.com/download/pdf/alecensa_prescribing.pdf. Revised January 2021. Accessed February 12, 2021.
- Alunbrig® (brigatinib) tablets [package insert]. ARIAD Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceuticals Company. Cambridge, MA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/208772s008lbl.pdf. Revised May 2020. Accessed November 16, 2020.
- Zykadia® (ceritinib) capsules [package insert]. Novartis. East Hanover, NJ. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/205755s011lbl.pdf. Revised November 2017. Accessed November 16, 2020.
- Xalkori® (crizotinib) capsules [package insert]. Pfizer, Inc. New York, NY. http://labeling.pfizer.com/showlabeling.aspx?id=676. Revised January 2021. Accessed February 12, 2021.
- Lorbrena® (lorlatinib) tablets [package insert]. Pfizer, Inc. New York, NY. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/210868s004lbl.pdf. Revised March 2021. Accessed March 11, 2021
- Crizotinib lowers testosterone in lung cancer patients. The Oncology Nurse website. https://www.theoncologynurse.com/ash-2017-itp?view=article&secid=11001:top-sec-11001artid=14887:top-14887. Posted April 27, 2020. Accessed November 16, 2020.
- Alvarez JG, Otterson GA. Agents to treat BRAF-mutant lung cancer. Drugs Context. 2019;8:21566. Accessed November 16, 2020.
- Tafinlar® (dabrafenib) capsules [package insert]. Novartis Pharmaceuticals Corporation, East Hanover, NJ. https://www.hcp.novartis.com/products/tafinlar-mekinist/. Revised May 2018. Accessed April 16, 2021.
- Hirsch FR, Suda K, Wiens J, Bunn PA Jr. New and emerging targeted treatments in advanced non-small cell lung cancer. Lancet. 2016:388(10048):1012-1024.
- Zhang Y-L, Yuan J-Q, et al. The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Onctotarget. 2016 Nov 29; 7(48): 78985-78993. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346692/. Accessed November 20, 2021.
- Gilotrif® (afatinib) tablets [package insert]. Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, CT. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/201292s014lbl.pdf. Revised January 2018. Accessed November 17, 2020.
- Vizimpro® (dacomitinib) tablets [package insert]. Pfizer Inc. New York, NY. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211288s000lbl.pdf. Revised September 2018. Accessed November 17, 2020.
- Tarceva® (erlotinib) tablets [package insert]. OSI Pharmaceuticals, LLC. Northbrook, IL. https://www.gene.com/download/pdf/tarceva_prescribing.pdf. Revised October 2016. Accessed November 17, 2020.
- Cyramza® (ramurcirumab) injection [package insert]. Eli Lilly and Company, Indianapolis, IN. https://pi.lilly.cm/us/cyramza-pi.pdf. Posted May 2020. Accessed November 17, 2020.
- Iressa® (gefitinib) tablets [package insert]. AstraZeneca Pharmaceuticals LP. Wilmington, DE. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/206995s003lbl.pdf. Revised August 2018. Accessed November 17, 2020.
- Tagrisso® (osimertinib) tablets [package insert]. AstraZeneca Pharmaceuticals LP. Wilmington, DE. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208065s008lbl.pdf. Revised April 2018. Accessed November 17, 2020.
- FDA approves osimertinib as adjuvant therapy for non-small cell lung cancer with EGFR mutations. U.S. Food and Drug Administration website. https://www.fda.gov/drug-approvals-and-databases/fda-approves-osimertinib-adjuvant-therapy-non-small-cell-lung-cancer-egfr-mutations. Posted December 18, 2020. Accessed December 21, 2020.
- MET. My Cancer Genome website. https://mycancergenome.org/content/gene/met/. Copyright 2017. Accessed May 12, 2020.
- Email exchange with Mark Awad, MD, PhD, Dana-Farber Cancer Institute, June 5, 2020.
- TabrectaTM (capmatinib) tablets [package insert]. Novartis Pharmaceuticals Corporation. East Hanover, NJ. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213591s000lbl.pdf. Revised May 2020. Accessed November 17, 2020.
- Tepmetko® (tepotinib) tablets [package insert]. EMD Serono, Inc. Rockland, MA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214096s000lbl.pdf. Posted February 3, 2021. Accessed February 4, 2021.
- NTRK1. My Cancer Genome website. https://mycancergenome.org/content/gene/ntrk1. Published 2017. Accessed November 17, 2020.
- Farago AF, Taylor MS, Doebele RC, et al. Clinicopathologic features of non-small cell lung cancer harboring an NTRK gene fusion. JCO Prec Oncol. 2018;2:PO.18.00037.
- RozlytrekTM (entrectinib) capsules [package insert]. 2019. Genentech USA, Inc. South San Francisco, CA. https://www.gene.com/download/pdf/rozlytrek_prescribing.pdf. Revised August 2019. Accessed November 17, 2020.
- Vitrakvi® (larotrectinib) capsules [package insert]. Loxo Oncology, Inc. Stamford, CT. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211710s000lbl.pdf. Revised November 2018. Accessed November 17, 2020.
- RET. My Cancer Genome website, https://mycancergenome.org/content/gene/ret/. Copyright 2017. Accessed November 17, 2020.
- Lin C, Wang S, Xie W, et al. The RET fusion gene and its correlation with demographic and clinicopathological features of non-small cell lung cancer: a meta-analysis. Cancer Biol Ther. 2015;16(7):1019-1028.
- Gavreto® (pralsetinib) capsules [package insert]. Blueprint Medicines Corporation. Cambridge, MA. https://accessdata.fda.gov/drugsatfda_docs/label/2020/213721s000lbl.pdf. Revised September 2020. Accessed November 17, 2020.
- RetevmoTM (selpercatinib) capsules [package insert]. Lilly USA, LLC, Indianapolis, IN. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213246s000lbl.pdf. Revised May 2020. Accessed November 17, 2020.
- Shaw AT, Ou SH, Bang YJ, et al. Crizotinib in ROS1-rearranged non-small cell lung cancer. The New England journal of medicine. Nov 20 2014;371(21):1963-1971. Accessed November 17, 2020.
- Camidge DR, Pao W, Sequist LV. Acquired resistance to TKIs in solid tumors; learning from lung cancer. Nature Reviews Clinical Oncology, 2014; 11:473-481. http://www.nature.com/nrclinonc/journal/v11/n8/abs/nrclinonc.2014.104.html. Accessed November 17, 2020.
- Schmid S, Fruh M, Peters S. Targeting MET in EGFR resistance in non-small cell lung cancer--ready for daily practice? Lancet Oncol. 2020;21(3):320-322.
- Marcoux N, Gettinger SN, et al. EGFR-Mutant Adenocarcinomas That Transform to Small-Cell Lung Cancer and Other Neuroendocrine Carcinomas: Clinical Outcomes. J Clin Oncol. 2019 Feb 1; 37(4) 278:285. Accessed November 17, 2020.
- Gao J, Li H-R, Jin C, et al. Strategies to overcome acquired resistance to EGFR TKI in the treatment of non-small cell lung cancer. Clin Transl Oncol. 2019;21(10):1287-1301. Accessed November 17, 2020.
- Lovly C. Combating acquired resistance to tyrosine kinase inhibitors in lung cancer. Am Soc Clinic Oncol Educ Book. 2015;e165-e173. Accessed November 17, 2020.
- Tan WL, Jain A, Takano A, et al. Novel therapeutic targets on the horizon for lung cancer. Lancet Oncol. Aug 2016;17(8):e347-362. https://www.thelancet.com/journals/lanoncl/article/PIIS1470-2045(16)30123-1/fulltext. Accessed November 17, 2020.
- Vyse S, Huang PH. Targeting EGFR exon 20 insertion mutations in non-small cell lung cancer. Sig Transduct Target Ther. 4, 5 (2019). https://doi.org/10.1038/s41392-019-0038-9. https://www.nature.com/articles/s41392-019-0038-9. Accessed June 1, 2021.
- RybrevantTM (amivantamab-vmjw) injection [package insert]. Janssen Biotech, Inc, Horsham, PA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761210s000lbl.pdf. Revised May 2021. Accessed May 30, 2021.
- Scheffler M, Ihle M, et al. K-ras mutation subtypes in NSCLC and associated co-occurring mutations in other oncogenic pathways. J Thorac Oncol. 2019;14(4):606-616. https://www.sciencedirect.com/science/article/pii/S1556086418335329. Accessed June 1, 2021.
- LumakrasTM (sotorasib) tablets [package insert]. Amgen, Inc, Thousand Oaks, CA. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214665s000lbl.pdf. Revised May 2021. Accessed May 30, 2021.
- Find the Unseen 13%. Amgen website. https://www.findkrasg12c.com/kras-g12c-inhibition. Posted November 2020. Accessed May 30, 2021.
- FDA approves mobercertinib for EGFR exon 20-positive mNSCLC. Targeted Oncology website. https://www.targetedonc.com/view/fda-approves-mobocertinib-for-egfr-exon-20-positive-mnsclc. Posted September 15, 2021. Accessed September 15, 2021.