Not all that long ago, chemotherapy was the only option to treat most advanced (metastatic) cancers. Because these drugs work by destroying rapidly dividing cells, they harm some healthy cells — such as hair follicles — as well as cancer cells. In the past two decades, cancer treatment has been transformed by targeted drugs and the emergence of immunotherapy. Targeted drugs are designed to home in on specific genes or proteins that are altered or overexpressed on cancer cells. Immunotherapy has been very successful for certain types of advanced cancers, such as lung, bladder, and skin cancers.
One form of immunotherapy is called an immune checkpoint inhibitor. It takes the brakes off immune cells, unlocking their ability to detect altered proteins on cancer cells in order to attack and kill these cells. These drugs include programmed death (PD-1)-inhibitors and PD-L1-inhibitors (such as pembrolizumab, atezolizumab, nivolumab), and cytotoxic T-lymphocyte antigen (CTLA)-4 inhibitors (ipilimumab).
The speed of FDA approvals for these drugs has outstripped the general understanding of their effects, and side effects, raising many questions for people who have cancer — and even for many physicians. If you're receiving immune checkpoint inhibitors, or wondering about them as part of cancer therapy, here are some facts you should know.
Does immunotherapy benefit all patients?
Immunotherapy benefits some, but not all, cancer patients. It seems to work better for certain cancers — for example, cancers with higher levels of PD-L1 protein or a massive number of gene mutations due to DNA repair defects. However, there are many exceptions, and we do not fully understand how best to select patients who will benefit.
How long does immunotherapy last?
Cancer cells adapt, building resistance to targeted therapies. When a tumor responds to immunotherapy, the remission tends to last a long time (a year or more), unlike a response to chemotherapy (weeks or months). Also, with immunotherapy, tumors initially may swell as immune cells engage with the cancer cells, then later shrink as cancer cells die. The early swelling is called psuedoprogression.
What about side effects?
All drugs have side effects, including the immunotherapy drugs discussed here. Understanding the information below can help if you or a loved one does experience side effects.
Does immunotherapy have serious side effects?
Immunotherapy with PD1/PD-L1 inhibitors is generally well tolerated, but serious side effects may occur. This happens in about 20% of people given PD1/PD-L1-inhibitors. It occurs in 40% to 60% of people given a combination of PD1-inhibitor and CTLA4-inhibitor immunotherapies.
Most side effects appear around two to three months after therapy starts. However, close monitoring, early recognition, and prompt therapy can help control side effects. Because immunotherapy drugs unleash immune cells, inflammation may occur in organs such as the colon (causing diarrhea), lungs (causing coughing or shortness of breath), skin (causing rash), liver (causing an elevation of liver enzymes in blood), thyroid gland (causing generally low, but sometimes high, thyroid hormone levels), and other areas of the body.
How are side effects of immunotherapy managed?
Severe side effects are controlled by stopping the immunotherapy and starting corticosteroids (such as prednisone), which are tapered slowly over a period of weeks. If you've had immunotherapy at any time in the past, report any new symptom to your treating oncologist before self-medicating with drugs purchased over the counter. For example, if you have diarrhea, taking loperamide (Imodium) may arrest the symptom. But it won't address the root cause, which is inflammation of the large intestine. Uncontrolled inflammation of the intestine may lead to rupture of the intestinal wall, which can be life-threatening. Similarly, if you have a cough, consuming cough suppressants allows lung inflammation to continue and become potentially life-threatening.
Do antibiotics affect how well immunotherapy works?
As we are beginning to better understand the immune system, an important nugget of emerging information is that antibiotics may reduce the ability of immunotherapy to kill cancer by killing harmless bacteria that live in the gut. People taking immune checkpoint inhibitors who receive antibiotics are less likely to benefit from immunotherapy than those who do not. Hence, it appears important to avoid unnecessary antibiotics for minor infections, which may be prescribed for patients visiting the ER for fever, cough, or other symptoms suggestive of infections. Check with your cancer team about this.
What do healthcare professionals need to know when I'm sick?
If you go to urgent care or the emergency room, tell health professionals about your cancer treatment. What type of cancer was diagnosed? When and where were you treated? What type of immunotherapy and other therapies did you receive? Also, ask your primary care doctor to include important information like this in your medical records. Remind health care providers about it if you're sick. You can use health apps to log the information, so you'll always have it handy if you need it.
To learn more about immunotherapy or join a clinical trial, talk to your cancer care team. You can also search for clinical trials on the National Cancer Institute website, or call 1-800-422-6237.
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