Treatment of Metastatic Non-Small-Cell Lung Cancer

Medically Reviewed by Jennifer Robinson, MD on January 11, 2023
5 min read

Once non-small-cell lung cancer (NSCLC) spreads far and wide, treating it is kind of a balancing act. A cure isn't likely, but you can slow it down. So you aim to relieve your symptoms and improve your quality of life with as few side effects as possible.

Newer therapies can help you do just that. And there are a lot more options today than just a few years ago. The number of tumors, where they are, and your overall health all come into play when deciding what to do.

Your doctor will start with a few tests to learn more about your NSCLC and help guide you to the best treatment.

Cancer comes about when a gene change causes a cell to grow and divide out of control. But you have so many genes, it's often hard to know which ones to blame.

With NSCLC though, doctors have tracked down a few of the culprits. When you have one of these known changes, you get targeted therapy. That means you take drugs that attack cancer cells in specific ways based on gene differences.

Your doctor will do a test to look for:

ALK gene change. If you have it, you'll get a drug that helps block it, such as:

  • Alectinib (Alecensa) 
  • Brigatinib (Alunbrig)
  • Ceritinib (Zykadia)
  • Crizotinib (Xalkori)
  • Lorlatinib (Lorbrena)

The most common side effects are minor changes in vision, upset stomach, throwing up, and diarrhea. For most people, these problems fall on the milder side.

EFGR gene change. You get a different set of drugs for this one, such as:

  • Afatinib (Gilotrif)
  • Amivantamab-vmiw (Rybrevant)
  • Dacomitinib (Vizimpro)
  • Erlotinib (Tarceva)
  • Gefitinib (Iressa)
  • Mobocertinib (Exkivity)
  • Necitumumab (Portrazza)
  • Osimertinib (Tagrisso)

They slow down how fast tumors grow and spread. Side effects include skin rash and diarrhea.

BRAF gene change. Two of the main drugs used for this one are dabrafenib (Tafinlar) and trametinib (Mekinist). They work in different ways, but both can be effective. They may cause itching, hair loss, and other issues.

MET gene defect. This non-inherited gene defect can cause something referred to as MET (mesenchymal-epithelial transition) exon 14 or METex14 skipping. Drugs approved for this treatment are capmatinib (Tabrecta) and tepotinib (Tepmetko). They may cause lung or breathing problems as well as liver issues.

NTRK gene defect: There are two drugs to use against a defect in the neurotrophic tyrosine receptor kinase (NTRK).

  • Entrectinib (Rozlytrek)
  • Larotrectinib (Vitrakvi)

They work by blocking the enzyme to help keep the tumor from growing. Common side effects include dizziness, fatigue, nausea, vomiting, constipation, weight gain, and diarrhea.

ROS1 gene change. Four drugs are approved to target the abnormal ROS1 protein.

  • Ceritinib (Zykadia)
  • Crizotinib (Xalkori)
  • Entrectinib (Rozlytrek)
  • Lorlatinib (Lorbrena)

Common side effects of ROS1 inhibitors include dizziness, diarrhea, constipation, fatigue, and changes in vision.

RET (Rearranged during transfection) gene change. There are two drugs now approved for RET-positive NSCLC and both are kinase inhibitors:

  • Pralsetinib (Gavreto)
  • Selpercatinib (Retevmo).

They work to block the enzyme and inhibit tumor growth. Some side effects include lowered white blood cell count, increased liver enzyme and blood sugar levels, as well as diarrhea and dizziness. There’s also the possibility of a decrease of levels of protein and calcium in the blood.

MET (mesenchymal-epithelial transition) gene change. Capmatinib (Tabrecta) is also a kinase inhibitor and is currently the only drug approved to treat this gene mutation. It works to stop growing and spreading to other parts of the body. Common side effects are fatigue, shortness of breath, swelling of limbs, nausea, and loss of appetite. Capmatinib could affect your liver function so your doctor will need to monitor.

KRAS (Kirsten rat sarcoma) gene mutation. This gene helps in the production of the K-Ras protein instructions which helps cells grow and multiply. There are two approved targeted therapies for tumors with any KRAS mutation: adagrasib (Krazati) and sotorasib (Lumakras).

Other gene changes. There's a growing list of gene defects that can cause NSCLC, but not all of them have targeted drugs. That's one reason to look into clinical trials, where researchers test new medicines.

Your doctor will check tumor cells for their level of a protein called PD-L1. If it's high, immunotherapy is often the best place to start. It uses your immune system -- your body's defense against germs -- to attack cancer cells.

You may take cemiplimab (Libtayo), nivolumab (Opdivo), or pembrolizumab (Keytruda). Atezolizumab (Tecentriq) and durvalumab (Imfinzi) may also be given to treat certain types of NSCLC with a high level of PD-L1. These drugs help your immune system find and fight off cancer cells.

Some typical side effects include tiredness, cough, stomach upset, rash, and joint pain.

Chemo is the standard treatment when you don't have a gene change or high PD-L1. It uses drugs to kill cancer cells. Its side effects include hair loss, mouth sores, stomach upset, and more.

There are several chemo drugs used for NSCLC. For the best results, your doctor gives you two at a time. If your body isn't strong enough for two, even one can be helpful. You usually get four to six cycles of chemo, each taking about 3 weeks.

Once you're finished with treatment, you might keep taking what's called a maintenance drug. This is often another chemo medicine. Some research shows that this can slow the cancer down and help you live longer.

Your doctor may also add in some other drugs along with your chemo meds:

  • For NSCLC, you might also take pembrolizumab (Keytruda), the immunotherapy drug. Or you might get bevacizumab (Avastin), another targeted drug. If so, you may keep taking one of these as your maintenance drug.
  • For squamous NSCLC, your doctor might suggest the targeted therapy drug necitumumab (Portrazza).

The brain, bones, and areas around the lungs are the most common places this cancer spreads. You'll get specific care based on where it ends up and what problems it causes.

In your bones, you may get radiation to curb pain. When it causes fluid to build up around your lungs, you might need a thin tube in your chest to drain it more easily.

If it's in just one other place, like your brain or adrenal gland, you might have surgery to remove the tumor.

Sometimes, the first therapy you try doesn't work as well as you'd hope. But you still have options.

If you started with immunotherapy, your doctor may suggest chemo. If you started with one set of chemo drugs, you might try another or add in targeted therapy. It depends on your health, how far the cancer has spread, and what you want from treatment.

This is also why you want to start an approach called palliative care early on. It aims to keep you as comfortable as possible and help you manage stress.