EGFR-positive lung cancers may be treated by methods tailored to this specific type. Biomarker testing allows oncologists to determine which targeted treatments will work best for a person.

Metastatic EGFR-positive lung cancer is stage 4 as it has spread to distant sites. This type of cancer is mostly adenocarcinoma, a type of non-small cell lung cancer (NSCLC).

Specific treatments are available for people with metastatic EGFR-positive lung cancer. These targeted therapies are more effective and often have fewer side effects. Genetic testing can help determine which types of treatment may be most effective.

At some point, the cancer may start to grow again. Due to this, oncologists generally recommend repeat biomarker testing. There may be a change in the genes of the cancer cell, and a better treatment may be available.

Over 200 mutations can affect the EGFR gene. It’s more common in non-small cell lung cancer.

EGFR mutations are more likely to occur in people who do not smoke, females, and those of Asian ethnicity. Among nonsmokers, EGFR mutations may be present in 36% of NSCLC cases.

The most common EGFR mutations respond to similar treatments. However, around 10% of people with EGFR-positive NSCLC will have a rarer mutation, which may mean that they do not consistently respond to the therapies that doctors use for this type of cancer.

An example of this is EGFR exon 20, which is present in 3% to 4% of NSCLCs. This specific mutation is also more likely in people who do not smoke and in Asian populations.

Advanced EGFR-positive lung cancer has different treatments from other types of NSCLC. Targeted therapies are most often used.

TKIs

An EGFR TKI medication will be part of the treatment for stage 4 NSCLC with an EGFR mutation.

Tyrosine kinase inhibitors (TKIs) are a class of medication that help reduce the activity of the EGFR protein, which promotes cell growth. Blocking this growth signal prevents or slows cancer cell growth.

A variety of TKI medications is available. The EGFR inhibitor a person receives depends on factors such as the oncologist, the specific lung cancer, and treatment goals.

Options may include:

First-generation EGFR-TKI

Second-generation EGFR-TKI

Third-generation EGFR-TKI

EGFR TKI medications may work for months or years. Although these drugs are not a cure, they can help slow or stop the growth of the cancer. Some research suggests that EGFR TKIs could be a better first-line treatment than chemotherapy.

EGFR exon 20

If a person has EGFR exon 20 insertion in their cancer cells as well as changes in the MET gene, which can contribute to resistance against EGFR-TKIs, a MET inhibitor such as capmatinib can be effective in combination with an EGFR-TKI.

TKI and angiogenesis inhibitor combination therapy

Combination therapy involves the use of a TKI alongside an angiogenesis inhibitor. This type of inhibitor reduces blood flow to a tumor, thereby blocking its growth.

Researchers have reported promising results with this combination of medications, suggesting it extends survival. Examples of anti-angiogenesis drugs include bevacizumab (Avastin) or ramucirumab (Cyramza).

Chemotherapy

In the past, chemotherapy was a first-line treatment for advanced stages of cancer. However, targeted therapies may offer better outcomes, especially with certain cancer cell types or when chemotherapy is ineffective.

Following biomarker testing, oncologists can identify which drugs are most likely to work. TKIs are often the best first-line treatment for EGFR-positive lung cancer. However, chemotherapy may still form a part of the treatment.

EGFR exon 20

If a person has the EGFR exon 20 mutation present in their cancer cells, then the first-line treatment is often chemotherapy with amivantamab (a monoclonal antibody) or Sunvozertinib (Zegfrovy) for metastatic NSCLC if platinum-based chemotherapy has not worked.

Radiation therapy

Radiation therapy may play a role when TKIs fail to work for metastatic EGFR-positive lung cancer.

Even when TKIs do work, research suggests that radiation therapy may still be helpful. Radiation therapy could increase the amount of time that the TKI keeps working.

Research is ongoing to better understand EGFR mutations in lung cancer. There are questions about why some do not respond to EGFR TKIs.

However, evidence suggests that most people often tolerate and respond well to osimertinib (Tagrisso). Many people will receive osimertinib as their first treatment.

Similarly, a 2023 systematic review and meta-analysis notes that osimertinib has the fewest side effects and is often a suitable first-line treatment.

While TKIs are a standard treatment for EGFR-positive lung cancer, cancer may develop resistance to these medications. As such, it is important to better understand the potential mechanisms of resistance and develop novel treatments that can target or bypass these resistance mechanisms.

Ongoing studies are also investigating how best to use chemotherapy, radiation therapy, and other medications. These other therapies may still play an important role by helping TKIs work even better.

A person can speak with their healthcare team to see if any clinical trials are taking place that they may want to participate in.

In the advanced stages of metastatic EGFR-positive lung cancer, targeted treatments for EGFR are often used.

Oncologists commonly prescribe TKIs as the first-line treatment, such as osimertinib. Other treatments include chemotherapy, radiation therapy, and anti-angiogenesis inhibitors.

The first steps of treatment are to determine the stage of cancer and carry out biomarker testing. A person’s healthcare team can then use this information to discuss the best options with an individual.