Immunotherapy is a type of treatment that aims to boost the body’s own immune system to fight cancer cells. In the immune system, the white blood cells, called T-cells, are responsible for fighting infections or cancer cells. However, cancerous cells can continue to change and can develop ways to stop or slow the normal T-cell response.1,2
The role of the PD-1 receptor
Researchers have identified pathways where cancer cells suppress the T-cell immune response. One of the pathways that are affected in some lung cancers is the PD-1 receptor and the proteins which bind to the receptor, PD-L1 and PD-L2. When this pathway is affected by the cancer cells, the cancer can grow and spread without being kept in check by T-cells.
The immunotherapy treatments developed to target the PD-1 pathway in non-small cell lung cancer (NSCLC) treatment include Keytruda® (pembrolizumab), Opdivo® (nivolumab), and Libtayo® (cemiplimab).2 Additional immunotherapies approved for the treatment of certain forms of NSCLC include Tecentriq (atezolizumab) and Imfinzi (durvalumab). Atezolizumab and durvalumab target the PD-L1 pathway.
Yervoy® (ipilimumab) is an immunotherapy drug used in combination with nivolumab to treat certain forms of NSCLC. It may be used as a first-line treatment for certain forms of metastatic (has spread to other parts of the body) or recurrent (has returned following treatment) NSCLC that has no EGFR or ALK tumor mutations.
In small cell lung cancer (SCLC), Tecentriq® (atezolizumab) and Imfinzi® (durvalumab) can be used in patients with extensive-stage SCLC as first line-treatment in addition to certain chemotherapy drugs.
How immunotherapies work
Pembrolizumab, nivolumab, atezolizumab, durvalumab, and ipilimumab are monoclonal antibodies. Antibodies are a normal part of the immune system that attach to antigens (such as germs) to mark them for destruction by the immune system. Monoclonal antibodies are created in a laboratory to attach to specific antigens on the surface of cancer cells. Keytruda, Opdivo, and Libtayo target the PD-1 receptor, blocking the binding and activation of PD-L1. Tecentriq and Imfinzi target the PD-L1 pathway, while Yervoy targets the CTLA-4 pathway. By blocking these pathways, the body’s immune system is able to fight the cancer.4
Side effects of immunotherapy agents
Like other treatments for cancer, immunotherapy drugs can cause side effects. The side effects vary by treatment and by patient. In general, immunotherapy agents may cause side effects that are similar to flu-like symptoms, such as fever, chills, nausea and appetite loss. Fatigue is another common side effect. Patients should discuss a comprehensive list of possible side effects of their individual treatment regimen with their doctor.3,4
Research in immunotherapy
Immunotherapy is one of the fastest growing areas of research in cancer treatment. There are several areas of research in immunotherapy, including:5
- Monoclonal antibodies, which target specific tumor antigens
- Checkpoint inhibitors, which target molecules that are involved in the regulation of immune responses
- Therapeutic vaccines, which help the immune system target tumor-specific antigens
- Adoptive T-cell transfer, in which the patient’s T-cells are removed, genetically modified, and then re-introduced into the body
In addition, research continues to identify the patients who will most benefit from immunotherapy agents and at what point during treatment these medications should be given for the best clinical outcome.2