Non-Small Cell Lung Cancer (NSCLC) is a common form of lung cancer. For many years, treatment options were often limited to traditional methods like chemotherapy, radiation, and surgery. However, the landscape of NSCLC treatment has transformed with the emergence of immunotherapy, an innovative strategy that harnesses the body’s own defenses to combat cancer.
Understanding Immunotherapy
The immune system acts as the body’s natural defense mechanism, constantly surveying for foreign invaders such as bacteria and viruses. Specialized immune cells work to identify and eliminate these threats, preventing disease. This protective system also plays a role in preventing the development of cancers by recognizing abnormal cells.
Cancer cells, however, can develop sophisticated ways to evade detection and destruction by these patrolling immune cells. They might disguise themselves as healthy cells, produce signals that suppress immune activity, or even remove the very proteins that immune cells use to recognize them.
Immunotherapy aims to overcome these evasion tactics by enhancing or restoring the immune system’s inherent ability to find and destroy cancer cells, effectively re-educating the body’s defenses to target the cancer.
How Immunotherapy Targets NSCLC
Immunotherapy specifically targets NSCLC by interfering with “checkpoints,” which are regulatory pathways that cancer cells exploit to hide from the immune system. T cells, a type of white blood cell, are designed to identify and eliminate abnormal cells, including cancerous ones.
However, cancer cells can express proteins like Programmed Death-Ligand 1 (PD-L1) on their surface. When PD-L1 on a cancer cell binds to Programmed Death-1 (PD-1) on a T cell, it sends an inhibitory signal that effectively “turns off” the T cell, preventing it from attacking the tumor.
Similarly, another checkpoint protein, Cytotoxic T-Lymphocyte-Associated protein 4 (CTLA-4), can also suppress T-cell activity, primarily by limiting their initial activation and proliferation in lymphoid tissues. Immune checkpoint inhibitors block these interactions. By blocking PD-1 or PD-L1, these drugs prevent the “off” signal, allowing T cells to remain active and destroy NSCLC cells. Blocking CTLA-4 helps to promote the expansion of anti-tumor T cells, further unleashing the immune response against the cancer.
Common Immunotherapy Medications for NSCLC
Several immunotherapy medications are commonly used for NSCLC, primarily falling into the categories of PD-1 or PD-L1 inhibitors.
PD-1 Inhibitors
PD-1 inhibitors, such as nivolumab (Opdivo), pembrolizumab (Keytruda), and cemiplimab (Libtayo), block the PD-1 protein on T cells, preventing cancer cells from deactivating them. This allows the immune system to attack the tumor.
PD-L1 Inhibitors
PD-L1 inhibitors, including atezolizumab (Tecentriq) and durvalumab (Imfinzi), target the PD-L1 protein found on some tumor cells and immune cells, activating the immune response against cancer cells. These medications can be used alone, in combination with chemotherapy, or with other immunotherapies.
CTLA-4 Inhibitors
CTLA-4 inhibitors, such as ipilimumab (Yervoy) and tremelimumab (Imjudo), block the CTLA-4 protein on T cells, which normally acts as a brake on immune activity. CTLA-4 inhibitors are typically used in combination with PD-1 inhibitors for NSCLC to enhance the overall immune response.
What to Expect During Treatment
Patient selection for immunotherapy often involves biomarker testing, particularly for PD-L1 expression on tumor cells. A higher expression of PD-L1 can indicate a greater likelihood of response to certain immunotherapy drugs. However, immunotherapy can also be effective in patients with low or negative PD-L1 expression, sometimes when combined with chemotherapy.
Immunotherapy drugs are administered intravenously. The duration of treatment varies, but for advanced NSCLC, it can sometimes continue for an extended period.
While generally better tolerated than traditional chemotherapy, immunotherapy can cause side effects. Common side effects may include fatigue, skin rashes, itching, diarrhea, and muscle or bone pain. More serious but less frequent side effects can involve inflammation of organs, such as colitis or pneumonitis. These side effects are managed by healthcare providers who monitor patients closely.
In some cases, patients may experience “pseudo-progression,” where imaging initially shows an increase in tumor size or new lesions. This is actually a sign of immune cell infiltration into the tumor, rather than actual cancer growth. True progression, however, is characterized by rapid tumor growth and worsening symptoms.