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NSCLC: advances in treatment
December 14, 2022

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Doctors once thought non-small cell lung cancer (NSCLC) was a disease. Most people received the same treatment—chemotherapy (chemo)—especially when their cancer had spread to other parts of the body.

Now doctors know there are many different types of NSCLC, and “more and more are coming,” says Nathan Pennell, MD, a medical oncologist specializing in breast cancer at Cleveland Clinic’s Taussig Cancer Institute.

This means treatment plans are no longer one size fits all. Instead, treatments such as targeted therapies and immunotherapy are tailored to each person’s tumor.

Targeted therapies

Some cancer cells have changes in genes (also called mutations) that help them grow and spread. The goal of several targeted therapies is to block these changes. The FDA has approved drugs to treat eleven different gene mutations that can cause NSCLC:

  • EGFR
  • ALK
  • BRAF
  • ROS1
  • RET
  • MET
  • KRAS
  • PIK3CA
  • HER2
  • NTRK
  • MEK1

A drug targets the growth of tumors on blood vessels:

The epidermal growth factor receptor – or EGFR – is the most common. It’s a protein on the surface of cells that helps them grow and divide. When you have too much EGFR, your cells grow faster than normal. Drugs called EGFR inhibitors stop this growth.

Karen Reckamp, ​​MD, is co-director of the Lung Cancer and Thoracic Oncology Program at City of Hope in Duarte, CA. She says that targeted therapy has completely changed the way doctors treat lung cancer. Well, before you start treatment for advanced NSCLC, you’ll likely have a genetic test done to determine if you have a mutation that could guide your treatment.

Reckamp says this new approach has changed the game for many people with advanced NSCLC.

“We’re not talking about a cure,” says Reckamp. “But the tumor is shrinking, people are feeling better, going back to work and having a better quality of life.”

Targeted therapies also have disadvantages. Some only work in the small number of people with gene mutations who respond to a specific targeted therapy. About 15% of people with lung cancer have EGFR-positive lung cancer. For other gene changes, the numbers are much smaller.

The drugs also have side effects, such as:

  • skin rash
  • Diarrhea
  • liver damage
  • Bone marrow problems

Reckamp says these aren’t usually as severe as chemotherapy side effects.

“For most people, the side effects are pretty tolerable, and they’re doing pretty well.”

Another problem is that targeted drugs often stop working eventually.

“Cancer cells find ways to survive and overcome the toxic treatments we give them,” says Reckamp. “If that happens, you need to try another treatment.”

Still, she says targeted therapies have greatly improved the odds for people with NSCLC.

“Only with the chemotherapy [extending life] around 1 year was as good as we could get. Now, with these therapies on top of chemotherapy, it is not uncommon for patients to live 2 or even 5 years.”

immunotherapy

Your immune system normally destroys cancer cells. But tumor cells are sneaky and can find ways to bypass your body’s best defenses. If you have NSCLC, some cancer cells can produce a protein called PD-L1. It binds to another protein, PD-1, on key T cells in the immune system. This is called an immune checkpoint, and it tells your T cells to leave the tumor alone.

One way to avoid this is to use drugs called checkpoint inhibitors. They prevent PD-L1 and PD-1 from coming together. This unleashes your immune system so that it can attack cancer cells with full force. But healthy cells get caught in the crossfire.

“Immunotherapy can cause inflammation anywhere in the body from head to toe,” says Reckamp. “If your immune system never shuts down, you can get something that resembles an autoimmune disease like rheumatoid arthritis. Or you may have problems with your thyroid, liver, bladder, kidneys, and heart.

“And that can happen at any time – even after you’ve finished treatment. But most symptoms are well controlled with high-dose steroids.”

Your doctor won’t suggest immunotherapy unless your tumor tests positive for high levels of PD-L1. However, the test is not always accurate, and some tumors that test positive for PD-L1 may not respond to immunotherapy.

Still, Reckamp says that despite the serious side effects and high price, immunotherapy is a better choice than chemotherapy for most people who have it. It may continue to work even after you have stopped taking it.

In the pipeline

Reckamp says to look for improvements in targeted drugs and smarter drugs that can outsmart cancer cells and survive.

“There are many clinical trials focused on overcoming resistance to targeted drugs and immunotherapy and combining that with chemotherapy, not just the length of one [person’s] life, but also the quality,” she says.

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NSCLC: advances in treatment
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