Immunotherapy in Lung Cancer, with Julie Brahmer, MD

April 28, 2015
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Today’s podcast is about new advances in immunotherapy for treating lung cancer, including the recent FDA approval of nivolumab to treat advanced squamous non-small cell lung cancer (NSCLC).



ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world's leading professional organization for doctors that care for people with cancer.

Today's podcast is about new advances in immunotherapy for treating lung cancer; including the recent FDA approval of nivolumab, to treat squamous non-small cell lung cancer. This podcast will be led by Dr. Julie Brahmer, Associate Professor of Oncology and Director of the Thoracic Oncology Program at The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, and clinical researcher for the lung cancer portion of the phase I trial for nivolumab.

ASCO would like to thank Dr. Brahmer for discussing this topic.

Dr. Brahmer: Hello. This is Doctor Julie Brahmer. I am a thoracic oncologist at Johns Hopkins, and I'm the Director of Thoracic Oncology here at The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.

Today, I'm going to talk with you about the immune system and lung cancer. Certainly, the field of immunotherapy has greatly changed over the past several years. By immunotherapy, I mean a type of treatment that uses the immune system to treat cancer, as well as other diseases.

I began my research career developing therapies for lung cancer. And about six years ago, I was approached to help develop some immune therapies called checkpoint inhibitors. Checkpoint inhibitors are antibodies that have been developed to block checkpoint pathways. And checkpoint pathways are those pathways that our normal immune system uses to control its response to infections or other things. The immune system uses these pathways typically to prevent immune diseases such as lupus or rheumatoid arthritis, but it also uses it to prevent overactive immune systems. But we know now that lung cancer and other cancers use these type of pathways to prevent the immune system from recognizing that the cancer is there, and prevent the immune system from attacking it. And these antibodies allow the brakes to be taken off the immune system or the cancer shield to be brought down in order for the immune system to work again against the cancer.

Certainly, we're very excited about a lot of this data that's coming out. Six years ago, when we started presenting some of this data most people were not enthusiastic and did not think this type of therapy would be applicable to larger groups of patients outside of patients with melanoma and kidney cancer. But as the data has come out across multiple different immune type of treatments that it consistently works in lung cancer, I think a lot of the skeptics are now more open to using this type of therapy. And particularly now, with the FDA approval of nivolumab, this is very exciting to finally have cracked that door open for patients with lung cancer, and giving them an option for a new type of treatment.

Nivolumab—which is the most recent antibody to be approved for use and the first antibody to be approved for use for lung cancer—is an checkpoint inhibitor. Nivolumab is an antibody that blocks the receptor on the T cell and this receptor's name is called the PD-1 receptor. PD stands for “Programmed Death 1,” and the PD-1 receptor on the T cell binds with ligand on a cancer cell. When that system binds together, that causes the T cells to go away, become inactive, and no longer able to attack the cancer. When antibodies, such as nivolumab, come in and block the ability of the cancer or the lung cancer to interact with the T cells and cause them to go away and become inactive by blocking that pathway, the T cells remain active, and able to recognize the cancers there, and be able to kill it. Certainly, we now know that compared to chemotherapy for squamous cell lung cancer patients, the nivolumab will improve survival, and particularly those patients who respond, that response is much longer lasting than we think than chemotherapy is, and resulting in the improved survival. We will hear more data about this hopefully this year, and again we hope to broaden this type of therapy and other therapies to all lung cancer patients.

I think certainly compared to other types of treatment options, immunotherapy is much different than what we consider for patients with lung cancer. Certainly it's different than chemotherapy, it's different than the tyrosine kinase inhibitors such as erlotinib or Tarceva or crizotinib and Xalkori. The hope is that this type of therapy, such as nivolumab, maybe, we hope that it's less toxic. Again, we have to see. And certainly, because it works differently, it will have different side effects, where with chemotherapy we expect potential nausea, potential drop in white blood cell count, potential hair loss. For nivolumab and drugs like that, we don't expect those type of side effects. The type of side effects patients can get with immune type of therapy is any immune type of side effects. So anything that ends in -itis, this type of antibody can cause, so inflammation of anything. Overall, the most common side effect for most patients is fatigue, but again, most of my patients say that it's not like the fatigue that you experience with chemotherapy. We know that some patients do extremely well with chemotherapy, but some patients do struggle with fatigue on chemotherapy. And in general, the immune type of therapies don't cause as much fatigue.

Because of these side effects relating to the immune system, we do follow various different laboratory values while a patient is on this type of therapy, and we also ask them a lot of questions. We follow patients' thyroid function because the immune system can attack the thyroid gland and cause low thyroid hormone levels, so we do follow that. We also ask patients about the amount of bowel movements that they have every day, because diarrhea can be caused by these type of antibodies, and this type of diarrhea is called colitis, or inflammation of the colon. We do keep a close eye on patients' bowel movements, so if we're asking about how many bowel movements do you have a day, and what potential side effects these are, we certainly want to know this type of information. We also ask about pain in the joints, we also ask about fevers, we ask about shortness of breath, things like that. Typically, though, in general, severe side effects are not that common.

However, if a patient does have very high inflammation, we do say that the patients may need to go on steroids, this is typically prednisone, and we also stop the drug. A lot of patients are concerned when we have to stop the antibody, but we do explain to everyone that when we stop an antibody like this, the effects of the antibody can last for weeks to months and not to worry that if it's working on the cancer, it should continue to work on the cancer even though we stopped the drug. We have not yet found that going on steroids causes any change in response to the treatment or cancer response to the treatment but definitely the steroids can decrease the amount of inflammation that occurs. But again, we typically don't start the steroids until a patient has had significant side effects, and again, that is much rarer compared to patient side effects on chemotherapy. Again, the nice thing about these sort of antibodies compared to the tyrosine kinase inhibitors, such as erlotinib or crizotinib, is that this type of antibody does not need to be taken every day for it to work.

Nivolumab is given by vein—so it's not a pill—once every two weeks. And again, in general, this is relatively easy to tolerate. I think that this type of therapy in general is going to revolutionize cancer therapy, but most of us want to try to raise the bar and make this type of therapy more applicable to patients with either other types of cancer or other types of lung cancer as well. Again we're hoping we see data for patients with non-squamous cell histology or adenocarcinoma as well as for patients with small cell lung cancer. We hope to have some of this data come out over the next year. We're hoping to see this information but right now the FDA has approved this type of therapy for patients with squamous cell lung cancer in the second line setting, and what that means is in the second line setting it means that patients with squamous cell lung cancer with metastatic disease have received the first type of chemotherapy and if their disease progresses or gets worse on the first type of therapy then they're eligible to get this type of therapy, the immune therapy. We remain very excited but while it helps a lot of patients with lung cancer, we want to make this more applicable to more patients with lung cancer and that's why a lot of us are very interested in doing clinical trials to try to improve on what we now know and use the power of drugs like nivolumab but improve on it.

ASCO: Thank you Dr. Brahmer. More information on lung cancer and immunotherapy can be found at And for more expert interviews and stories from people living with cancer, visit the Cancer.Net Blog at

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