Targeted Therapies for Lung Cancer

Knowing if you have ALK-positive lung cancer has the most treatment implications for advanced stage lung cancer patients. Patients with advanced-stage ALK-positive lung cancer will likely be prescribed an ALK-inhibitor, also called a tyrosine kinase inhibitor (TKI), at some point in their treatment. These types of drugs work to stop or inhibit cancer growth by targeting the error in the ALK gene.

Some patients with early-stage ALK-positive lung cancer who’ve had surgery may receive an ALK-inhibitor called Alectinib (Alecensa). It can be given with or without chemotherapy.

To learn more about ALK treatment options, visit the ALK Treatment Options page.

For patients with advanced-stage NSCLC with BRAF V600E mutations, two combinations of BRAF and MEK inhibitors are effective as a first-line treatment. These types of targeted therapy work to stop or inhibit cancer growth by targeting the errors in the BRAF and MEK genes:

• Dabrafenib (Taflinar) plus trametinib (Mekinist)
• Encorafenib (Braftovi) plus binimetinib (Mektovi)

Patients whose cancer grows after first-line treatment may receive immunotherapy with or without chemotherapy. 

The standard of care for patients with a different BRAF mutation (non-V600E) is immunotherapy with or without chemotherapy. All BRAF patients should ask their doctors about clinical trials.

EGFR-positive lung cancer has been widely studied, and therefore several treatment options exist. As researchers learn more, treatment recommendations may change. Our EGFR Treatment page explores current treatment options, but each patient's situation is unique. Work closely with your doctor to decide on the most appropriate treatment for your specific type of lung cancer.

• Exon 20 insertion mutations are resistant to standard EGFR tyrosine kinase inhibitors (TKIs), which are drugs that are used to block cancer growth. If you are diagnosed with the EGFR exon 20 mutation, your first-line treatment option will likely include chemotherapy with amivantamab (Rybrevant), a type of targeted drug called a monoclonal antibody. Sunvozertinib (Zegfrovy) is also an FDA-approved treatment for EGFR exon 20 insertion NSCLC post-platinum chemotherapy (approved in July 2025).
• If your cancer grows after treatment, you should get another biopsy to see if a different biomarker has developed. If a new biomarker has been identified, your doctor will recommend a targeted therapy to treat that biomarker. 
• If no new biomarker is found, your doctor may recommend one of the following options: 
  • Chemotherapy alone or with amivantamab (if you haven’t already received it)
  • Chemotherapy with another monoclonal antibody called bevacizumab (Avastin) 
  • Immunotherapy
• All lung cancer patients should ask their doctors if they are eligible to participate in a clinical trial.

Right now, treatment is available for patients who have a type of HER2 mutation called a HER2 exon 20 insertion mutation. Treatment for advanced-stage lung cancer with this mutation is chemotherapy with or without immunotherapy, followed by a targeted therapy (given through IV) called fam-trastuzumab deruxtecan (Enhertu). Some patients may receive a different targeted drug called ado-trastuzumab emtansine (Kadcyla), which is approved for breast cancer but sometimes used in HER2-positive lung cancer. Zongertinib (Hernexeos), is a kinase inhibitor, for adults with unresectable or metastatic NSCLC, whose tumors have HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-approved test, and who have received prior systemic therapy. Sevabertinib (Hyrnuo) is available for the treatment of adult patients with locally advanced or metastatic, nonsquamous NSCLC whose tumors have HER2 (ERBB2) tyrosine kinase domain activating mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy. 

Treatment for advanced-stage HER2 amplification depends on the amount of HER2 in the tumor. Some patients may receive fam-trastuzumab deruxtecan (Enhertu) after prior treatment with chemotherapy (with or without immunotherapy).

Many other HER2-targeted medications are being studied in clinical trials. Ask your doctor if a clinical trial is right for you.

Currently, the standard first-line therapy for a patient with KRAS-positive lung cancer depends on the stage of their cancer. Treatment may include surgery, radiation, chemotherapy, immunotherapy or a combination.

For patients with KRAS G12C, there are currently two approved targeted therapy pills, also called KRAS inhibitors. If a patient’s cancer stops responding to chemotherapy or immunotherapy, or a combination both, targeted drugs sotorasib (Lumakras) or adagrasib (Krazati) may be recommended. 

There are many other medicines being studied in clinical trials to treat KRAS-positive lung cancer. All patients with lung cancer should discuss clinical trials with their doctor. 

For patients whose lung cancer has spread, the standard of care for first-line treatment of MET exon 14 skipping is one of the targeted therapy MET inhibitor drugs: capmatinib (Tabrecta) or tepotinib (Tepmetko). Telisotuzumab vedotin-tllv (Emrelis, AbbVie Inc.) is approved for adults with locally advanced or metastatic, non-squamous non-small cell lung cancer (NSCLC) with high c-Met protein overexpression (50% or greater). Other treatment options may include other MET inhibitors currently being studied in clinical trials, chemotherapy and immunotherapy. Some physicians may recommend immunotherapy and/or chemotherapy before the MET inhibitors. 

If you have MET gene amplification, you may receive immunotherapy with or without chemotherapy. Other lines of treatment may include clinical trials of MET inhibitors.

Much is being studied about MET alterations. All patients with lung cancer should talk to their doctors about clinical trials.

Knowing if you have an NTRK gene fusion is important no matter your stage of lung cancer. However, it has the most treatment implications for stage four patients.

Currently, the approved targeted therapies for NTRK gene fusions in lung cancer are entrectinib (Rozlytrek), larotrectinib (Vitraki) and Augtyro™ (repotrectinib). These drugs are given in pill form and work by directly targeting, or inhibiting, the gene fusion that is making the cancer grow.

Other treatment options for patients with NTRK gene fusions may include clinical trials, chemotherapy or chemotherapy plus immunotherapy.

It is important to know that NTRK gene fusions are different than NTRK mutations. A fusion is when two genes join, and a mutation is a change in the gene sequence. Think of DNA like words in a book, a fusion is two words stuck together, while a mutation is words out of order.

Both fusions and mutations can cause uncontrolled cell growth which can lead to cancer, but currently, only NTRK gene fusions have treatments available. Treatment for NTRK mutations is still being studied in clinical trials. Researchers are also examining if patients who have an NTRK gene fusion who later develop an NTRK mutation are less likely to respond to the NTRK-inhibitor drugs. Talk with your doctor about participating in a clinical trial.

Knowing if you have an NRG1 gene fusion is important no matter your stage of lung cancer. However, it has the most treatment implications for stage four lung cancer. Patients with advanced-stage NSCLC whose cancer continues to grow after other treatments, may be eligible for a targeted medication called zenocutuzumab-zbco (Bizengri). This medication is given through an IV. Other treatment options for NRG1 gene fusions are currently being studied in clinical trials.  

If you do not test positive for a biomarker with an approved targeted therapy, traditional chemotherapy, immunotherapy or a combination of the two may be recommended. Surgery or radiation may also be recommended. It may also be appropriate to enroll in a clinical trial looking at treatments for a number of other markers. 

Not every person is eligible for targeted therapies for lung cancer. However, the only way to find out is through biomarker testing. There are different types of biomarker tests, including next-generation sequencing (NGS), which looks for many biomarkers at one time. All lung cancer patients should talk with their doctor about biomarker testing to make sure patients receive the most appropriate treatment for their specific type of lung cancer. 

Knowing whether your lung cancer has a RET rearrangement is important no matter your stage of lung cancer. However, it has the most treatment implications for advanced-stage lung cancer patients. 

First-line treatment for RET rearrangements for advanced-stage lung cancer patients are specific drugs that target, or inhibit, RET. Currently, selpercatinib (Retevmo) and pralsetinib (Gavreto) are the two FDA-approved RET inhibitors. 

Over time, the cancer may change, and the RET inhibitor may stop working. If this happens, your doctor might recommend clinical trials, chemotherapy or immunotherapy. Some patients may receive chemotherapy with or without immunotherapy first and a RET-inhibitor second.

Knowing if you have ROS1-positive lung cancer is important no matter your stage of lung cancer. However, it has the most treatment implications for patients with advanced-stage lung cancer. Treatment implications tell you what your test results means for your treatment, which therapies are likely to work best for you, and what your care team may recommend next.

Research on ROS1-positive lung cancer, and treatment plans may vary from patient to patient. The treatment a patient receives and the order in which it is given, depends on the type of ROS1 fusion, how well the patient tolerates the medication and if the cancer has spread to the brain. Below is a high-level overview of treatment options for ROS1-positive lung cancer, but your personal treatment plan may be different.