Expert Q&A: Immunotherapy for Metastatic Lung Cancer

This year, more than 228,000 people in the United States will learn they have lung cancer, and more than 142,000 will die from this disease. Just a few years ago, the outlook for metastatic lung cancer was grim. Once the cancer had spread outside the lungs, only about 5% of people survived for 5 years.

But thanks in large part to new immunotherapy drugs like atezolizumab (Tecentriq), durvalumab (Imfinzi), nivolumab (Opdivo), and pembrolizumab (Keytruda), people with metastatic lung cancer are living longer than ever before.

Julie Brahmer, MD, a lung cancer expert at the Johns Hopkins Kimmel Cancer Center, explains how immunotherapy works and how it has improved the outlook for people with metastatic lung cancer.

WebMD: How is immunotherapy being used to treat metastatic lung cancer?

Brahmer: Immunotherapy is approved for the first-line treatment of patients with metastatic lung cancer who have high levels of PDL-1. PDL-1 is a protein some lung cancers release to prevent the immune system from attacking them. The higher the PDL-1 level is, the more likely the cancer will respond or shrink from immunotherapy.

Today, doctors are combining immunotherapy drugs with chemotherapy to see if we can increase the chance of tumor shrinkage and long-term cancer control. That has expanded the use of immunotherapy to metastatic lung cancer patients with lower levels of PDL-1, or no PDL-1 on their cancer.

WebMD: How does immunotherapy work compared to older cancer treatments like chemotherapy and radiation?

Brahmer: Chemotherapy and radiation act directly on the cancer, either by damaging the DNA of cancer cells or by preventing them from dividing. Immunotherapy uses your own immune system to treat the cancer.

Our bodies have a pathway that prevents our immune system from attacking healthy cells. Some cancers use that pathway to prevent the immune system from attacking them. Immunotherapy drugs block this pathway and allow the immune system to attack the cancer. It's like taking the brakes off your immune system.

WebMD: How significantly does immunotherapy help prolong people's lives?

Brahmer: People with metastatic lung cancer have an average survival time of 12 months. Immunotherapy doubles the survival time to just over 2 years.

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While it's not common, some patients with metastatic lung cancer can be cured, or their cancer can be very well-controlled for a long period of time. Being diagnosed with stage IV lung cancer is no longer a death sentence. We just have to figure out how to refine therapies to increase the chance of that being true for each individual patient.

WebMD: How does this treatment affect people's quality of life?

Brahmer: Compared to chemotherapy, there are a lot fewer side effects and an improved quality of life with immunotherapy. The side effects are completely different, but in general, immunotherapy is easier to tolerate.

WebMD: What are the side effects from immunotherapy?

Brahmer: The most common side effect is fatigue. The next most common side effects are rash, itching, and diarrhea, which we can give steroids to treat. When you start combining immunotherapy drugs to increase the chance of the immune system attacking the cancer, then we see higher rates of side effects. With immunotherapy, some of the side effects can be long-lasting. For example, if your immune system attacks your thyroid gland, more than likely you'll need to be on thyroid hormone long-term. There are also increased side effects if you add immunotherapy drugs to chemotherapy.

The interesting thing is, if patients have these kinds of side effects and they have to stop taking the immunotherapy drug, their disease can still respond. Your immune system can develop memory and continue to keep the cancer under control, even if you're no longer receiving the drug.

WebMD: Are there any reasons why people with advanced lung cancer shouldn't get this treatment?

Brahmer: Patients who have an active autoimmune disease like lupus, rheumatoid arthritis, or multiple sclerosis may not be able to take immunotherapy drugs. It really depends on how bad their autoimmune disease is, and what medicine they're on to control it. You have to have a discussion with your doctor about the pros and cons of these drugs, and the risks of flaring your autoimmune disease.

Someone who has had a liver, heart, or lung transplant can't take immunotherapy drugs. Because we're stimulating the immune system, there's a higher chance of organ rejection. Someone with a kidney transplant should have a conversation with their doctor about whether they're willing to go back on dialysis, and the other risks involved.

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In patients who have mutations like EGFR or ALK in their cancer, the likelihood of responding to immunotherapy drugs is relatively low. We prefer to use drugs that target those mutations first, and save immunotherapy, either in combination with chemotherapy or by itself, for down the road.

WebMD: How much does immunotherapy cost, and does insurance cover it?

Brahmer: Medicare and standard health insurance should cover the cost, because immunotherapy is FDA-approved for metastatic lung cancer. The cost really depends on your copay and what your insurance covers. Someone who has a high copay may pay thousands of dollars. And someone who doesn't have insurance may not be able to afford these drugs.

WebMD: What happens if the drug stops working? Are there other treatments?

Brahmer: What drug you take next depends on what you've received before. Right now, we often use chemotherapy in that situation, but clinical trials are looking at combinations of immunotherapy or other ways to get around treatment resistance. If treatment has stopped working for you, I'd highly encourage you to join a clinical trial that's testing combinations of different drugs.

WebMD Feature Reviewed by Michael W. Smith, MD on September 23, 2019

Sources

SOURCES:

American Cancer Society: "Key statistics for lung cancer."

Julie Brahmer, MD, lung cancer expert, Johns Hopkins Kimmel Cancer Center.

The ASCO Post: "WCLC 2019: Pooled analysis of CheckMate 017 and 057: 5-year outcomes with nivolumab vs docetaxel in previously treated NSCLC."

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