Most targeted drugs work only if you have certain gene mutations, which your doctor can test you for, says Dr. Gheeya. If there are no mutations present, that’s when a person would receive chemo or immunotherapy, he adds. Here are the common mutations that may be treated with targeted therapies for lung cancer.
EGFR Mutations
Epidermal growth factor receptor (EGFR) is a protein found on the surface of cells, and a mutation in the cancer gene can lead to an abnormal protein, causing lung cancer. Some mutations in the EGFR gene can be treated with drugs, such as:
- afatinib (Gilotrif)
- amivantamab (Rybrevant)
- dacomitinib (Vizimpro)
- erlotinib (Tarceva)
- gefitinib (Iressa)
- osimertinib (Tagrisso)
ALK Fusion
About 5 percent of NSCLCs have an alteration in the anaplastic lymphoma kinase (ALK) gene. When mutated, it can cause abnormal cell growth and spread. Drugs that target ALK changes include:
- alectinib (Alecensa)
- brigatinib (Alunbrig)
- ceritinib (Zykadia)
- crizotinib (Xalkori)
- lorlatinib (Lorbrena)
ROS1 Fusions
The ROS1 gene arrangement is related to the ALK gene, and some drugs that work for one also work for the other. In July 2026, the FDA approved a new second-line ROS1 treatment, zidesamtinib, for those with locally advanced or metastatic ROS1 NSCLC who have received a prior ROS1 treatment.
- ceritinib (Zykadia)
- crizotinib (Xalkori)
- entrectinib (Rozlytrek)
- lorlatinib (Lorbrena)
- repotrectinib (Augtyro)
- taletrectinib (Ibtrozi)
- zidesamtinib (Jideytro)
BRAF Mutations
The BRAF gene helps manage important cell functions related to growth. When mutated, it signals cells to divide uncontrollably. Two drug combinations are approved by the U.S. Food and Drug Administration (FDA) to target changes in the BRAF V600E gene:
- dabrafenib (Tafinlar) and trametinib (Mekinist)
- encorafenib (Braftovi) and binimetinib (Mektovi)
KRAS Mutations
The KRAS gene helps regulate cell growth, serving as an on-off switch. Similar to the BRAF mutations, when mutated, KRAS allows cells to grow uncontrollably. KRAS mutations are one of the most common mutations linked to cancer, driving 32 percent of lung cancers. There are several types of KRAS mutations. KRAS G12C can be targeted by FDA-approved agents. Examples include:
- adagrasib (Krazati)
- sotorasib (Lumakras)
MET Alterations
Only around 5 percent of patients who have lung cancer have this gene mutation. For those who do, targeted therapy MET inhibitor drugs, such as capmatinib (Tabrecta) or tepotinib (Tepmetko) may be recommended treatments.
RET Mutations
An error in the RET gene, sometimes called a rearrangement, can be a biomarker for lung cancer, although it appears in only 1 to 2 percent of patients. Patients who have this mutation are often younger and have never smoked. The two FDA-approved RET inhibitors are selpercatinib (Retevmo) and pralsetinib (Gavreto).
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