Immunotherapy is changing the landscape of therapy for patients with cancer and is resulting in a new population of cancer survivors for whom survivorship issues will need to be evaluated and addressed.
The basics of immunotherapy, its potential side effects, and the role of navigation in supporting patients and their caregivers were presented by Jennifer Klemp, PhD, MPH, at the East Coast Regional Meeting of the Academy of Oncology Nurse & Patient Navigators.
Cancer immunotherapy is intended to stimulate the T cells to fight cancer. When the immune system detects a threat, T cells recognize the invading bodies by surface proteins called receptors. In the case of a virus, the T-cell receptor attaches itself to the virus and envelops the invading body and destroys it.
“The reason this T cell can do its job is because it recognizes that that virus is not part of our natural flora,” said Dr Klemp, Associate Professor of Medicine, Division of Oncology, University of Kansas Medical Center, Kansas City. “It’s not supposed to be there, and it [the T cell] knows it’s not supposed to be there.”
Cancer cells, however, pose a different problem by avoiding detection by the immune system. They evade T cells by hiding from and suppressing the activity of the T-cell receptors. Once cancer cells evade detection by the T cells, the cancer cells can continue to multiply and spread to other tissues.
How Does Immunotherapy Work?
Immunotherapy drugs called checkpoint inhibitors, such as nivolumab and pembrolizumab, remove the blockade on T-cell receptors, thereby unleashing the T cells that are resident within the tumor microenvironment. This action permits the T cells to destroy the cancer cells.
There are currently several T-cell targets for immunoregulatory antibody therapy for a range of tumor types that includes melanoma, non–small cell lung cancer, urothelial/bladder cancer, gastrointestinal cancer, head and neck cancer, renal cell carcinoma, breast cancer, and hematologic malignancies.
President Jimmy Carter represents one example of the use of immunotherapy for metastatic melanoma. At age 90, he was diagnosed with metastatic melanoma, and tumors were identified on his liver and brain, and he was given weeks to live. His treatment regimen consisted of surgery, stereotactic radiation, and immunotherapy with pembrolizumab.
Once he declared himself cancer free, “everybody calls your cancer center saying, ‘hey, can I have what President Carter had?’ Everybody with metastatic diseases was lighting up your phones,” said Dr Klemp, who is also Director of Cancer Survivorship, University of Kansas Cancer Center.
“When you think about our older cancer population, we don’t include them in clinical trials,” she continued. “We don’t always have the greatest options for them, but this could be a next step, not just for our younger patients or patients who are on a third, fourth, fifth line, but this could be a nice option for our older patients as well.”
Types of Immunotherapy
Several types of immunotherapy exist, with differing mechanisms of action.
Vaccines
Vaccines are designed to stimulate the patient’s immune system to fight against the cancer. Some therapeutic cancer vaccines contain a recombinant protein comprised of a tumor antigen and an immune cell activator. Once administered, antigen-presenting cells (APCs) process the antigen and then express antigenic fragments on their surface for presentation to the patient’s T cells. These activated APCs interact with naive T cells to initiate a T-cell–driven immune response.
Monoclonal Antibodies
Monoclonal antibodies elicit a direct or indirect immune response that leads to cell death. Mechanisms of action include blocking signaling pathways needed for tumor cell growth, triggering an immune-mediated cytotoxic response, or blocking angiogenesis.
Tumor-specific monoclonal antibodies are being used in the treatment of leukemia, and breast, colorectal, and head and neck cancers, demonstrating improvements in overall survival and progression-free survival in randomized, phase 3 clinical trials.
Adoptive T-Cell Therapy
Adoptive T-cell therapy includes chimeric antigen receptor T-cell therapies in which T cells are removed from the patients and genetically engineered to augment T-cell activity. Patients are first treated with lymphodepleting chemotherapy followed by infusion of billions of modified T cells, with the goal of enabling the immune system to attack the tumor with an army instead of on its own.
“If we can give radiation or chemotherapy, that allows the body to become more immunocompromised, and the therapies can be more effective,” said Dr Klemp. “The goal in this case, again, is to compromise the patient, modify the DNA, and hopefully have the patient be able to fight better against the tumor.”
Immune Checkpoint Inhibition
Immune checkpoint inhibition releases the brakes on T cells applied by checkpoint proteins. Nivolumab, for example, is a blocking antibody that binds to a T-cell surface immune checkpoint protein called programmed death-1 (PD-1), preventing its interaction with its inhibitory ligand PD-L1. By this action, the T cells within the tumor are unleashed. Other immune checkpoint inhibitors, such as ipilimumab, increase the number of tumor-reactive T cells available to infiltrate the tumor and are being used in combination with agents such as nivolumab.
Patients whose tumors have high expression for PD-L1 may respond better to immune checkpoint inhibitors. This and other biomarkers could perhaps identify up front the patients more likely to respond to immunotherapy. At present, immunotherapy tends to be administered as second- or third-line therapy, ie, in a heavily pretreated population.
Older patients may have a heightened response to cancer immunotherapy, Dr Klemp explained. In President Carter’s case, instead of first having to use lymphodepleting chemotherapy to make immunotherapy more effective, his advanced age already rendered him immunocompromised. “His age was one of his biggest strengths in the treatment process,” she said.
Immunotherapy can cause a variety of side effects, including fatigue; nausea; mouth sores; diarrhea; hypertension; and fluid buildup, usually in the legs. The side effects of immunotherapy are often greatest with the first cycle and generally become less severe with subsequent treatments.
Role for Navigation
Game-changing immunotherapy means managing disease in a different group of survivors. Nurse navigators have a responsibility to provide education about the side effects of immunotherapy and to give the patients the tools up front to manage side effects should they arise.
“As you think about where we’re going with treatment, how do we expand our role? It is our job to make sure that patients have a good mode of communication, that our teams are aware of these latent long-term effects from their treatment,” Dr Klemp said.
Managing expectations is an important part of education. The growing awareness of the effectiveness of President Carter’s immunotherapy may lead patients to believe that the treatment he received will cure their disease.
Effective communication must also include the caregivers. “As we think about some of our geriatric populations, you better make sure that their caregivers are equally as informed, obviously, as the patient,” she said.
Educational videos specific to the side effects of immunotherapy can be helpful. The University of Kansas Cancer Center has its own YouTube channel that presents not only news but also patient education materials. “That way, it’s your team talking to your patients,” Dr Klemp said. “These are very cheap alternatives to help us extend our reach to our patient populations and their caregivers.”
Treatment options or the aggressiveness of managing side effects may depend on the patient’s life goals, which should be determined in a conversation with the cancer patient, especially if metastatic disease is present. A patient may want to live long enough or have a quality of life high enough to attend a daughter’s wedding or a grandchild’s graduation. Knowing the patient’s goals may also help to know when to consider enrollment into a clinical trial for an investigational therapy.
There are more than 1300 ongoing clinical trials in cancer immunotherapy, an indication of how rapidly the field is moving. The University of Kansas Cancer Center employs a clinical trial navigator to traverse the maze of clinical trials. “That’s an important role because we need to be screening every single patient that walks in our door,” she said. “I know from our own role, having a survivor navigator as well, we see a lot of patients as early as possible, and we encourage them to be part of clinical trials. It’s all of our responsibility to think about this journey that our patients take.”
Many of the immunotherapy agents that are currently reserved for later lines of therapy may be moved up when more clinical trial data become available, Dr Klemp said.
