Immunotherapy for lung cancer is a new type of treatment that aims to enhance the body’s immune response and stop the lung cancer from evading the immune system.
To help you understand and share this information, click here to download and print a booklet that summarizes the detailed information in the following sections. This booklet was produced in March 2015, before the October 2015 FDA expanded indication for nivolumab (Opdivo®) and approval of pembrolizumab (Keytruda®). For updated information about those two drugs, please see the Immune Checkpoint Inhibitors section below.
Find out more about how the immune system works, how treatments to boost it can help fight lung cancer, and whether participating in a clinical research study using immunotherapy might be a good option for you.
What is the immune system?
The following video explains what the immune system is and what it does.
The immune system is a network of cells, tissues, and organs that work together to protect the body from foreign invaders such as 1or . The key players in defending the body are a specific type of called lymphocytes. There are three types of lymphocytes: , , and .
Lymphocytes grow and develop in the 1, , and . They can also be found in clumps throughout the body, primarily as . (Lymph nodes in the neck are called cervical lymph nodes, and those between the lungs in the middle of the chest are known as mediastinal lymph nodes.) Clumps of lymphoid tissue are also found in the appendix, tonsils, and . The lymphocytes circulate through the body between the organs and nodes via and blood vessels. In this way, the immune system works in a coordinated manner to monitor the body for germs and other abnormal cells.
How does the immune system work?
A key feature of the immune system is its ability to tell the difference between the body's own normal cells, or "self," and cells and other substances that are foreign to the body, or "non-self." Every cell in the body carries a set of distinctiveon its surface. These identifying surface proteins let the immune system know that they are cells that belong to the body. They can be compared to the uniforms a football team wears. In the same way the uniform helps the quarterback know who is on his team, the proteins let the immune system know which cells belong in the body.
Healthy cells display normal proteins on their surface. The immune system has learned to ignore normal proteins.2 If the surface proteins are abnormal, such as when a virus infects cells or when cells become cancerous, they can be recognized by the immune system. Proteins recognized by the immune system are called .
If asubstance—such as a bacteria, virus, or cell—is recognized, the immune system kicks in to try to deal with it. It is the “non-self” antigens on the surface of these cells (the other team’s uniform) that the immune system identifies as abnormal. The immune system is great at recognizing bacteria and virus cells, because they look very different from healthy cells. On the other hand, tumor cells started as healthy cells and can look a lot like healthy cells. As a result, the body may have a harder time recognizing tumor cells as foreign.
In other instances, the immune system may recognize a tumor antigen but may be unable to mount a response strong enough to destroy the tumor. As cancers grow they can evolve ways to escape from attack by the immune system. For these reasons, many people with healthy immune systems still develop cancer and cancer still progresses.3 In many people with cancer, the cancer cells co-exist with immune cells capable of killing the cancer, but the cancer cells hold the immune cells back from working the way they should.1,2
What is the role of the immune system in cancer?
The following video explains how the immune system fights cancer.
The immune system has two responses that work together to detect and destroy cancer cells:and adaptive immune response.
The innate immune response is the first line of defense. The innate immune system’s normal function is to protect the body from initial invasion by bacteria and viruses, such as when bacteria invade broken skin or viruses land in the throat. The system includes natural killer (NK) cells, a type of lymphocyte that patrols the body and is on constant alert, looking for foreign invaders and abnormal cells. If cells from the innate immune system recognize a cancer cell as abnormal, they can attach to it and immediately release toxic chemicals that kill it. NK cells and other cells of the innate immune system do not need to recognize a specific abnormality on a cell to be able to do their job.
If the bacteria, viruses, or cancer cells evade the innate response, then the adaptive immune response becomes active.4 The adaptive immune response recognizes specific abnormalities on cancer cells that make them different from the cells that are naturally found in the body. Though it is more effective than the innate immune response, the adaptive immune response takes longer to become activated. The cells of the adaptive immune response include the other two types of lymphocytes: B cells and T cells.
B cells are like the body's military intelligence system, seeking out their targets and sending defenses to lock onto them. They react to “non-self” antigens by making proteins called. Antibodies are proteins that can attach to foreign and abnormal cells and let the body know that they are dangerous. Antibodies can kill cancer cells in several ways, including binding natural killer (NK) cells to the cancer.
T cells are the major cells the body uses to recognize and destroy abnormal cells. Once a foreign antigen or abnormal cancer protein has been recognized by T cells, the T cells rapidly increase in number. An army of T cells can be formed; these T cells are specifically designed to attack and kill cells that have foreign antigens.
If the immune system recognizes the lung tumor cells and can destroy them, why are lung tumors able to grow? Research has shown that some tumors enable their own growth by turning off the immune response. Immune responses beyond what is normal or necessary can be toxic, so T cells have many normal methods to dampen themselves down and essentially turn themselves off. This may allow the growth and development of tumor cells despite the presence of T cells with the potential to kill cancer cells.
What is immunotherapy?
Biological therapies use substances made from living organisms to treat disease. These substances either already exist in nature or are manmade in a laboratory.
Immunotherapy is considered a type of. It aims to enhance the body’s immune response and stop lung cancers from escaping from the immune system. Immunotherapy is a treatment that strengthens the natural ability of the patient’s immune system to fight cancer. Instead of targeting the person’s cancer cells directly, immunotherapy trains a person’s natural immune system to recognize cancer cells and selectively target and kill them.
Immunotherapies do this in one of two ways: (1) by enabling the immune system to mount or maintain a response or (2) by suppressing factors that prevent the immune response. There are many different types of immunotherapy. Three main types are currently being studied in people with 4: immune checkpoint inhibitors, therapeutic cancer vaccines, and adoptive T cell transfer. Immune checkpoint inhibitors have made the most progress at this time, and the first FDA-approved immunotherapy drugs for lung cancer belong to this group. Immunotherapy is also being studied in .
What types of immunotherapies are being studied for use in lung cancer?
Three main types of immunotherapies are currently being studied in people with non-small cell lung cancer (NSCLC): immune checkpoint inhibitors, cancer vaccines, and adoptive T cell therapy. Immune checkpoint inhibitors have made the most progress at this time. Immunotherapy is also being studied in small cell lung cancer (SCLC), although this research is in earlier phases.6
Below we discuss the three types of immunotherapies currently being studied.
Immune checkpoint inhibitors
The following video provides information on immune checkpoint inhibitors.
What is an immune checkpoint?
Many lung cancers co-exist with T cells capable of killing the cancer cells. However, the immune system has many normal mechanisms for dampening itself down. The immune system has fail-safe mechanisms that are designed to suppress the immune response at appropriate times in order to minimize damage to healthy tissue. These mechanisms are called immune checkpoint pathways. They are essentially the brakes on the immune system.
The challenge is that cancer cells are able to use these immune checkpoint pathways to lessen the immune response at the wrong times. This may allow cancer cells to thrive.5
How do immune checkpoint inhibitors work?
The immune checkpoint inhibitors work by targeting and blocking the fail-safe mechanisms of the immune system. Their goal is to block the immune system from limiting itself, so the original anti-cancer response works better.5
What immune checkpoint inhibitors are FDA-approved?
Platinum-based chemotherapies include carboplatin and cisplatin.
There are three immunotherapy drugs available outside clinical trials for people with lung cancer.
Nivolumab (Opdivo®): Approved for patients with metastatic NSCLC whose lung cancer has progressed on or after platinum-based chemotherapy7
- Pembrolizumab (Keytruda®): Approved for patients with metastatic non-small cell lung cancer (NSCLC) in the following situations8:
- As first-line treatment for patients whose tumors have a high PD-L1 expression Tumor Proportion Score (TPS) greather than or equal to 50% with no EGFR or ALK mutation and no prior systemic chemotherapy treatment for metastatic NSCLC. Approximately 30% of patients with newly diagnosed metastatic NSCLC will have tumors with this high level of PD-L1 expression.
- For patients whose tumor expresses PD-L1 (TPS greater than or equal to 1%) with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK mutations should have disease progression on FDA-approved therapy for these mutations before receiving pembrolizumab.
- Atezolizumab (Tecentriq®): Approved for patients with metastatic NSCLC in the following situations9:
- Their lung cancer has progressed during or after being treated with platinum-containing chemotherapy
- For patients with ALK-positive or EGFR-positive NSCLC, their lung cancer should have progressed on an approved ALK or EGFR inhibitor before they are treated with Tecentriq.
Some of the other drugs being developed include:
|Generic Name||Brand Name (in US)||Types of lung cancer
|Durvalumab (MEDI4736)||To be determined||NSCLC|
|Avelumab (MSB0010718C)||To be determined||NSCLC|
|PDR001||To be determined||NSCLC|
|REGN2810||To be determined||NSCLC|
|Tremelimumab||To be determined||NSCLC|
How are they administered?
Infusion time and schedules may vary depending on the drug.
- Nivolumab (Opdivo) is given intravenously over 60 minutes every 2 weeks.
- Pembrolizumab (Keytruda) is given intravenously over 30 minutes every 3 weeks
- Atezolizumab (Tecentriq) is given intravenously over 60 minutes every 3 weeks
How well do anti-PD-1/anti-pd-l1 drugs work?
Patients whose tumors have high levels of PD-L1 expression are more likely to respond to PD-1/PD-L1 therapies. However, even those with tumors that do not express PD-L1 may respond to these treatments.
In research studies of patients with non-small cell lung cancer that have been published to date, approximately 15%-20% overall have responded to immune checkpoint inhibitors. This includes patients who test negative for PD-1 and PD-L1, as well as those who test positive. In clinical trials, people who tested negative, as well as those who tested positive, have responded to immune checkpoint inhibitors. There are many reasons to think that the response rate will improve as researchers learn how best to use these drugs.
Researchers are looking for many ways to increase the number of people who respond to this treatment. In, they are combining treatments, boosting the immune system, and using other strategies.
How long does it take to see results from therapy with anti-PD-1/anti-pd-l1 drugs?
Of the approximately 15%-20% of patients in clinical trials with immune checkpoint inhibitors who have responded, about half have seen their tumors respond in 6 to 8 weeks. However, another half of the patients may take a much longer time to produce a response, possibly as long as 6 months.7,11,12,13,14,15,16
In a small subset of patients, the tumor on a 17may seem to get worse at first and then get better, or there may seem to be new areas of tumor. Doctors have coined the term pseudoprogression to describe this situation. One theory of why this happens is that, as the lymphocytes come in to attack a tumor, the tumor gets larger, and then, as they kill cancer cells, the tumor gets smaller again. The current thinking is that the tumors get larger because a large number of the patient’s T cells move into the tumor to clean it up. Therefore, some tumors that look larger on and scans are larger because the immune system is attacking the cancer, not because the cancer cells are growing.
In cases like this, the best course of action will likely be based on a number of factors. If the patient’s scan looks worse but the person is feeling fine, the doctor and patient may decide together to do another course of immunotherapy. If the scan looks worse and the person is feeling worse, then it may not make sense to continue with this type of therapy. In this case, the patient may need another kind of therapy to control the symptoms.
What are the side effects of immune checkpoint inhibitors?
The most common side effects seen with nivolumab (Opdivo) are fatigue, dyspnea, musculoskeletal pain, decreased appetite, cough, nausea, and constipation.7
The most common side effects seen with pembrolizumab (Keytruda) are fatigue, rash, joint pain, and cough.8
The most common side effects seen with atezolizumab (Tecentriq) are fatigue, decreased appetite, nausea, and urinary tract infections.9
There currently is no way to predict who will and won’t get these side effects. For more about managing treatment side effects, visit the Survivor Resource Center.
A side effect seen with some immune checkpoint inhibitors in lung cancer is pneumonitis, which is inflammation of the lung tissues that may lead to difficulty breathing if not treated early and correctly.7,8,18
Pneumonitis and some of the other side effects seen with immune checkpoint inhibitors are related to “turning on” the immune system, which then may also attack some healthy cells and cause inflammation. Other examples of this include:
- and renal dysfunction
- Inflammation of the , like the thyroid
Inflammation of the thyroid can cause either high or low thyroid hormone levels (hyperthyroidism or hypothyroidism). Inflammation of the liver can also occur, so liver function tests may be run periodically to check for that.
About half of patients develop some inflammation-related side effects. These are usually easy to manage, but sometimes patients may need to take additional medications, including corticosteroids or thyroid hormone replacement.7,8,9,18 It’s important for patients to let the doctor or nurse know if they are experiencing any problems while on treatment, so they can sort out whether the side effects are related to treatment or not.
It is especially important for patients to be very clear with their doctor about the side effects that they are experiencing, because this may impact future treatment plans.
Some patients experience side effects that are severe enough that they need to stop taking the immunotherapy treatment. In general, based on what has been seen with patients in clinical research studies to date, these kinds of treatments are well tolerated by most patients.6,8,10,13,14,15,16,17,18
Because these drugs have been studied in patients for only a few years, we do not know for certain what the long-term side effects are in patients with profound responses, including remission of cancer. However, doctors have some ideas about what they may be18:
- One potential long-term side effect from immunotherapy may be that, if it affects the endocrine gland, a patient may need thyroid hormone supplementation for the rest of his or her life
- Some patients develop diabetes and need to be on medication
It’s important for patients to tell their doctor if they were ever treated with immunotherapy, even a long time ago, because side effects can show up after long periods of time.
Where do the anti-PD-1/anti-PD-L1 immune checkpoint inhibitors fit in the treatment plan for lung cancer?
Nivolumab (Opdivo) is currently approved for treating patients with 7non-small cell lung cancer who have been or are being treated with platinum-based .
Pembrolizumab (Keytruda) is currently approved for first-line treatment of patients with metastatic non-small cell lung cancer whose tumors express PD-L1 at a high level (Tumor Proportion Score [TPS] greater than or equal to 50%), as determined by an FDA-approved test. It is also approvwed for patients with tumors that express PD-L1 with a TPS of greater than or equal to 1% who have disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK mutations should have disease progession on FDA-approved therapy for these mutations before receiving pembrolizumab.8
Atezolizumab (Tecentriq) is currently approved for patients with metastatic non-small cell lung cancer who have been or are being treated with platinum-based chemotherapy. Patients with EGFR or ALK mutations should have disease progession on FDA-approved therapy for these mutations before receiving atezolizumab.9
In addition, these and other immune checkpoint inhibitors are being studied in patients with 6, , , , or non-small cell lung cancer in clinical trials.
The inhibitors are being studied in non-small cell lung cancer typesand . There are also clinical trials looking at these agents for .
Immune checkpoint inhibitors are being used alone and in combination with other therapies, including chemotherapy,, radiation therapy, another checkpoint antibody, or other immunotherapies.
To find out whether a patient is a candidate for one of the available clinical trials, the patient should ask his or her oncologist what clinical research studies are available locally and what research studies the oncologist recommends. If the oncologist does not have a clinical trial of his or her own available, the doctor may be able to help patients find another place that is enrolling patients in a trial. A patient may have to travel to get to a clinical trial if the immunotherapy is being given by someone other than the primary oncologist.
What patients need to know about themselves:
- The type of treatment for lung cancer they have had so far
- The line of therapy they are looking for
- Patients who have never been treated before should look for a
- Patients who have had prior chemotherapy for metastatic disease may be looking for a
- Patients who have had multiple lines of therapy will want a clinical trial that allows for that situation
Can immune checkpoint inhibitors be used in someone with a pre-existing autoimmune disorder?
Can Immunocompromised Patients be treated with immune checkpoint inhibitors?
- A certain level of white blood cell (WBC) count
- A certain level of lymphocyte count. This treatment is trying to make a person’s lymphocytes more active. Therefore, an extremely low lymphocyte count may mean the immune checkpoint inhibitor would not work, but scientists are still learning about that.
What are other considerations?
Patients who already take daily steroids, like prednisone or dexamethasone, are usually not eligible to participate in immune checkpoint inhibitor clinical research studies. People may be on that type of medication to keep another disease under control, like emphysema or COPD, or to try to control swelling from brain metastasis. However, some studies do allow steroid use if it is taken at a very low and stable dose.
Depending on the clinical trial, being on this kind of immunotherapy may prevent patients from going in additional immunotherapy trials, but that depends on the specific clinical trial. Patients who are doing well afterward should be able to participate in other clinical trials. Patients should talk to their doctor about this before beginning any new clinical research study.6,17
Therapeutic cancer vaccines
What is a therapeutic cancer vaccine?
When most people think of a vaccine, they think of a traditional vaccine given to prevent an infectious disease such as measles or polio. In addition to the traditional vaccines, there are two types of cancer vaccines. A preventive cancer vaccine is given to prevent cancer from developing in healthy people. For example, the hepatitis B vaccine is given to children to protect against a hepatitis B viral infection, which can lead to liver cancer. In contrast, a therapeutic cancer vaccine is given to treat an existing cancer by causing a stronger and faster response from the immune system.19 Most commonly, they are used in patients in remission in an attempt to prevent likely or the cancer from returning.
How do they work?
A therapeutic cancer vaccine is made from a patient’s own tumor cells or from substances taken from the tumor cells. They are designed to work by activating the cells of the immune system to recognize and act against the specific antigen on the tumor cell.19 Because the immune system has special cells for memory, the hope is that the vaccines will also help keep the lung cancer from coming back.3
Therapeutic cancer vaccines being studied in lung cancer include6:
|Generic Name||Brand Name (in US)||Types of lung cancer
|GV1001||To be determined||NSCLC|
|TG4010||To be determined||NSCLC|
|Dribbles (DPV-001)||To be determined||NSCLC|
|CIMAvax-EGF||To be determined||NSCLC|
|INGN||To be determined||SCLC|
For more information about research studies of vaccines in lung cancer, visit the National Cancer Institute Clinical Trials website.
How is a therapeutic cancer vaccine administered?
Therapeutic cancer vaccines are given as an injection either right below the skin’s top layer (intradermally), beneath the skin (subcutaneously), or into the muscle (intramuscularly). Early on in the study, the vaccines are given from one to three times a week. The doses are then spread out to every other week and, eventually, to every other month. The studies range from 1 to 3 years.6
Results of therapeutic cancer vaccine administration
Several studies have suggested that therapeutic cancer vaccines may be most effective when given in combination with other forms of cancer therapy. In addition they may even increase the effectiveness of the other treatments. There is also evidence that when patients have a large amount of disease, the immune system may become overwhelmed. Therefore, surgical removal of the tumor prior to administration of a cancer vaccine may make it easier for the immune system to develop an effective response.18,19 A major question going forward is whether vaccines will make anti-PD-1 immune checkpoint inhibitors more effective.
Where do therapeutic cancer vaccines fit in a lung cancer treatment plan?
Presently therapeutic cancer vaccines are being studied for both small cell and non-small cell lung cancer. They are being investigated as first-line therapy, 6, and . They are being tested alone and in combination with chemotherapy and radiation therapy.
What side effects have been seen in clinical studies?
The most commonly reported side effect of therapeutic cancer vaccines is inflammation at the site of the injection, including redness, pain, swelling, warming of the skin, itchiness, and occasionally a rash. Flu-like symptoms, including fever, chills, weakness, dizziness, nausea or vomiting, muscle ache, fatigue, headache, and occasional breathing difficulties, have also been reported after administration of a therapeutic cancer vaccine.19 For more about managing treatment side effects, visit the Survivor Resource Center.
More serious health problems have been reported in a smaller number of people after receiving a therapeutic cancer vaccine, but these may not have been caused by the vaccine. They include asthma, appendicitis, 19, and certain autoimmune diseases, including arthritis and . Rarely, severe allergic reactions to specific vaccine ingredients have been seen following vaccination.
Adoptive T cell transfer
What is adoptive T cell transfer?
Adoptive T cell transfer is being developed as a new approach to cancer treatment. The goal is to improve the ability of a person’s ownto fight cancer.
A sample of T cells is removed from the patient and then genetically changed in order to make the T cells more active against specific cancer cells. Scientists can change what is on the surface of the T cells. For example, they can add a receptor to the surface of the T cell that will target a specific antigen on a cancer cell. The receptors work like very specific Velcro that allows T cells to stick to cancer cells and kill the cells. The T cells are then returned to the patient and the altered T cells quickly home in on their targets.20
How does adoptive T cell transfer work?
Typically during an immune response, T cells multiply. After the initial response, most of the newly made T cells are eliminated. This keeps the total T cell number in the body at a normal level. The normal level of T cells is usually not high enough to sustain a response strong enough to effectively fight cancer.21
However, there is evidence that T cells have the ability to multiply in abundance when given to someone whose immune system has been weakened. Therefore, in an adoptive T cell transfer, patients are given chemotherapy prior to the adoptive T cell transfer in order to suppress their immune system. Once the chemotherapy is completed and the immune system is weakened, billions of modified T cells are reintroduced into the patient. The goal of the T cell transfer is to enable the immune system to attack the tumors in a large number that is otherwise impossible and in a way that it is incapable of doing on its own.22
A number of phase 1 and 2 clinical trials using adoptive T cell transfer for lung cancer are currently available. Find out what clinical research study options are available.
How are T cells removed from and returned to a patient?
The three ways of performing adoptive T cell transfer are:
- Collecting a sample from the actual tumor and multiplying the T cells in a laboratory
- Taking T cells from the bloodstream through a procedure called and genetically altering them to attack cancer cells that have specific
- Taking T cells from the body and changing them with special receptors, called chimeric antigen receptors (CARs). CARs recognize specific proteins found on the surface of cancer cells. The CAR T cells then bind to the cancer cells that have those proteins and destroy them
After any of these, the T cells are then returned to the patient through an 23.
Results of clinical trials involving T cell transfer
Small clinical trials using adoptive T cell transfer have generated some remarkable responses in patients with acute lymphocytic leukemia and lymphoma. Most patients’ cancers disappeared entirely, and several of these patients have remained cancer-free for extended periods.22,24,25 Whether T cell therapy will eventually prove to be as effective in lung cancer is unknown.
Where does adoptive T cell transfer fit in the treatment plan for non-small cell lung cancer?
Adoptive T cell transfers can be considered only in patients whose tumor expresses one of the antigens being studied. Currently it is being studied by itself, in combination with chemotherapy, and with concurrent administration of interleukin-2. These studies are being conducted in patients who have tumors that have not responded to prior therapies and for whom no alternative treatment is available.6
What side effects have been seen in clinical studies?
Common side effects of adoptive T cell transfer are pain, swelling, soreness, redness, itchiness, and rash at the site of infusion. Flu-like symptoms including fever, chills, weakness, dizziness, nausea or vomiting, muscle or joint aches, fatigue, headache, occasional breathing difficulties, and change in blood pressure may also occur.
In addition to the more common side effects, lowered blood counts can also occur. This leads to a risk of severe or even fatal allergic reaction to T cell transfer.25
A very serious side effect of adoptive T cell therapy is cytokine-release syndrome; this is a rapid and large scale release of 23into the bloodstream. Cytokines are chemical messengers that help the T cells carry out their duties. Too many cytokines can lead to dangerously high fevers and quick drops in blood pressure.
For most patients in clinical trials, side effects have been mild enough to be managed with standard supportive treatments, including steroids. Patients with more severe reactions have been successfully treated with anti-inflammatory drugs like etanercept (Enbrel®) and tocilizumab (Actemra®).24
For more about managing treatment side effects, visit the Survivor Resource Center.
What clinical research study (clinical trial) options are available?
Many clinical trials are ongoing to study these different types of immunotherapy and answer key questions, including:
- Does any one of the immunotherapies work better alone or in combination with other treatments?
- Should immunotherapy be given before or after another treatment?
- When in the treatment of non-small cell lung cancer should the immunotherapy be used?
There are many 6, , and studies currently under way that will add to our understanding of immunotherapies.
If you are considering participating in a clinical trial, start by asking your doctor whether there is one for which you might qualify in your area. In addition, here are several resources to help you find one that may be a good match for you:
- LUNGevity Lung Cancer Clinical Trial Matching Service through Emerging Med: 800-698-0931 http://www.emergingmed.com/networks/LUNGevity/
- National Cancer Institute website: http://www.cancer.gov/clinicaltrials/search
- Coalition of Cancer Cooperative Groups website: http://www.cancertrialshelp.org/cancer-trial-search/
Learn more about clinical trials here.
Questions to ask about clinical trials
- What are the benefits and risks of participating in an immunotherapy clinical trial?
- How will I be monitored while participating in a clinical trial?
- What are my responsibilities during the clinical trial?
- Are there any costs associated with my participation in a clinical trial?
- Where can I learn more about clinical trials?
- Who can I speak with if I have questions during the clinical trial?
- What happens if I decide I do not want to participate in the clinical trial at some point?
Updated November 3, 2016.
- Immune system. National Institute of Allergy and Infectious Diseases website. https://www.niaid.nih.gov/topics/immunesystem/Pages/default.aspx. Updated January 20, 2016. Accessed February 23, 2016.
- Immunotherapy: Using the Immune System to Treat Cancer. National Cancer Institute website. http://www.cancer.gov/research/areas/treatment/immunotherapy-using-immune-system. Updated September 14, 2015. Accessed February 23, 2016.
- Cancer and the Immune System: The Vital Connection. Cancer Research Institute website. http://www.cancerresearch.org/CRI/media/Content/Cancer%20Immunotherapy/Cancer-and-the-Immune-System-The-Vital-Connection.pdf. Published 2003. Accessed February 23, 2016.
- Vansteenkiste JF and Shepherd FA, “Section 50: Immunotherapy and Lung Cancer,” The IASLC Multidisciplinary Approach to Thoracic Oncology, IASLC Press, 2014, pp. 691-704.
- Pardoll D. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012; 12:252-264. doi:10.1.1038/nrc3239. http://www.nature.com/nrc/journal/v12/n4/full/nrc3239.html. Accessed February 22, 2016.
- Clinicaltrials.gov. US National Institutes of Health website. http://clinicaltrials.gov. Accessed February 22, 2016.
- Opdivo® (nivolumab) injection [package insert]. Bristol-Myers Squibb Company. Princeton, NJ; March 2015. http://packageinserts.bms.com/pi/pi_opdivo.pdf. Revised January 2016. Accessed February 22, 2016.
- Keytruda® (pembrolizumab) injection [package insert]. Merck & Co., Inc. Whitehouse Station, NJ; 2014. http://www.merck.com.product/usa/pi_circulars/k/keytruda_pi.pdf. Revised October 2016. Accessed October 26, 2016.
- Tecentriq® (atezolizumab) injection [package insert]. Genentech, Inc., South San Francisco, CA; 2016. https://www.gene.com/download/pdf/tecentriq_prescribing.pdf. October 2016. Accessed October 25, 2016.
- Cancer Immunotherapy: Lung Cancer. Cancer Research Institute website. http://www.cancerresearch.org/cancer-immunotherapy/impacting-all-cancers/lung-cancer. Updated October 2015. Accessed February 23, 2016.
- Yervoy® (ipilimumab) injection [package insert]. Bristol-Myers Squib. Princeton, NY; 2011. http://packageinserts.bms.com/pi/pi_yervoy.pdf. Revised October 2015. Accessed February 23, 2016.
- Chustecka Z. ‘Exciting Times’ With Immunotherapy in Lung Cancer. Medscape Medical News website. http://www.medscape.com/viewarticle/813526. Published October 31, 2013. Accessed February 23, 2016.
- West HJ, Brahmer JR. Nivolumab Continues to Deliver in Lung Cancer [An ASCO Poster Brief]. Medscape Oncology website. http://www.medscape.com/viewarticle/806795. Published June 24, 2013. Accessed February 23, 2016.
Garon E, et al. Pembrolizumab for the treatment of non-small cell lung cancer. New England Journal of Medicine. 372(21): 2018-28. http://nejm.org/doi/full/10.1056/NEJMoa1501824. Published May 21, 2015. Accessed February 23, 2016.
Trial Yields Positive Data on Pembrolizumab for Lung Cancer, Potential Response Biomarker. National Cancer Institute. http://www.cancer.gov/news-events/cancer-currents-blog/2015/pembrolizumab-biomarker. Published April 27, 2015. Accessed February 23, 2016.
Soria JC, et al, “Efficacy and Safety of Pembrolizumab (MK-3475) for Patients with Previously Treated Advanced NSCLC Enrolled in KEYNOTE-001,” presented at 2015 European Cancer Congress (ECC), September 22-29, 2015, Vienna, Austria.
- Helwick C. Strong Showing for Anti-PD-1 Agents in Non-Small Cell Lung Cancer. The ASCO Post website. Volume 5. Issue 11. http://www.ascopost.com/issues/july-10-2014/strong-showing-for-anti-pd-1-agents-in-non-small-cell-lung-cancer/. Published July 10, 2014. Accessed February 23, 2016.
- Harvey RD. Immunological and Clinical Effects of Targeting PD-1 in Lung Cancer. Clinical Pharmacology & Therapeutics. 2014 Aug; 96(2): 214-223. doi:10.1038/clpt.2014.74. http://onlinelibrary.wiley.com/doi/10.1038/clpt.2014.74/full. Published April 1, 2014. Accessed February 23, 2016.
- Chow LQM. Exploring Novel Immune-Related Toxicities and Endpoints with Immune-Checkpoint Inhibitors in Non-Small Cell Lung Cancer. 2013 ASCO Educational Book website. http://meetinglibrary.asco.org/content/181-132. Accessed February 23, 2016.
- Fact Sheet: Cancer Vaccines. National Cancer Institute website. http://www.cancer.gov/cancertopics/factsheet/Therapy/cancer-vaccines. Reviewed December 18, 2015. Accessed February 23, 2016.
- Biological Therapies for Cancer. National Cancer Institute website. http://www.cancer.gov/cancertopics/factsheet/Therapy/biological. Reviewed June 12, 2013. Accessed February 23, 2016.
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