Immunotherapy represents an innovative approach to cancer treatment, fundamentally shifting how the disease is combated. Rather than directly targeting cancer cells with harsh chemicals, this therapy leverages the body’s own immune system to identify and eliminate malignant cells. This method has become a significant treatment option for various advanced cancers, including Stage 4 lung cancer, offering new possibilities for patients. It stands apart from traditional therapies by focusing on enhancing the natural defenses already present within the body.
What Immunotherapy Is and How It Works
The immune system typically serves as the body’s vigilant protector, designed to recognize and neutralize foreign invaders like bacteria and viruses. It achieves this through specialized cells, such as T-cells, which patrol the body and can distinguish between healthy cells and those that are abnormal or infected. This finely tuned recognition process is a cornerstone of the body’s defense mechanisms.
Cancer cells, however, possess an ability to evade this immune surveillance. They can develop mechanisms to hide from immune cells or send signals that effectively “turn off” the immune response. One common evasion tactic involves exploiting immune checkpoints, which are molecules on immune cells that normally act as “brakes” to prevent the immune system from overreacting and attacking healthy tissues. Cancer cells can manipulate these checkpoints, tricking the immune system into ignoring them.
Immunotherapy works by re-engaging the immune system’s ability to detect and destroy cancer cells. Many immunotherapy drugs, particularly immune checkpoint inhibitors, block these “brake” signals. By doing so, they release the natural immune response against the tumor, allowing T-cells to recognize and attack the cancerous cells more effectively. This process removes the cloaking mechanism cancer cells use, enabling the immune system to resume its intended function of eliminating threats.
Key Immunotherapy Approaches for Lung Cancer
In the context of lung cancer, immune checkpoint inhibitors are the most widely used immunotherapy approach. These therapies target specific proteins that cancer cells or immune cells use to suppress the immune response. By blocking these interactions, the immune system’s anti-tumor activity is unleashed.
One prominent class targets the PD-1 (Programmed Death-1) protein on T-cells or its ligand, PD-L1 (Programmed Death-Ligand 1), found on cancer cells. When PD-1 binds to PD-L1, it inhibits T-cell activity, allowing cancer cells to escape detection. Drugs like pembrolizumab (Keytruda), nivolumab (Opdivo), and cemiplimab (Libtayo) work by blocking the PD-1 protein on immune cells, while atezolizumab (Tecentriq) and durvalumab (Imfinzi) target the PD-L1 protein on cancer cells. These medications prevent the “turn-off” signal, thus activating the T-cells to attack the tumor.
Another approach involves targeting the CTLA-4 (Cytotoxic T-Lymphocyte-Associated Protein 4) checkpoint, which also acts as a brake on T-cell activation. Ipilimumab (Yervoy) is an example of a CTLA-4 inhibitor. This drug blocks CTLA-4, leading to increased T-cell activity and a stronger anti-tumor response. Combining a CTLA-4 inhibitor with a PD-1 inhibitor, such as nivolumab and ipilimumab together, can sometimes provide an even more robust immune activation against the cancer.
Beyond checkpoint inhibitors, other emerging immunotherapy strategies are being explored for lung cancer. Bispecific T-cell engagers, such as tarlatamab (Imdelltra), are engineered antibodies that bring T-cells and cancer cells into close proximity, facilitating the T-cells’ ability to kill the tumor. This specific therapy has been approved for extensive-stage small cell lung cancer. While CAR-T cell therapy, which involves genetically modifying a patient’s T-cells to better recognize and fight cancer, is also under investigation in clinical trials, it is not yet FDA-approved for lung cancer.
Treatment Considerations and Side Effects
Immunotherapy drugs are typically administered intravenously, meaning they are given through a drip into a vein. Patients usually receive these infusions in an outpatient setting, such as a chemotherapy day unit. The frequency of treatments can vary depending on the specific drug and treatment plan, often ranging from every two to six weeks.
While immunotherapy offers significant benefits, it can lead to unique side effects, often referred to as immune-related adverse events (irAEs). These side effects occur because the activated immune system, now uninhibited, can sometimes mistakenly attack healthy tissues and organs in the body. The severity and type of irAEs can vary widely among individuals.
Common side effects include fatigue, skin rashes, and diarrhea. More serious irAEs can involve inflammation of various organs, such as the lungs (pneumonitis), liver (hepatitis), or thyroid gland (thyroiditis). Other potential immune-related toxicities can affect the colon, kidneys, or endocrine glands, leading to conditions like colitis or hypophysitis. Management of these side effects often involves corticosteroids to suppress the immune response and reduce inflammation, or in some cases, temporary cessation of immunotherapy.
Integrating Immunotherapy into Stage 4 Lung Cancer Care
For patients with Stage 4 lung cancer, immunotherapy has become a preferred first-line option, either alone or in combination with chemotherapy, especially for non-small cell lung cancer (NSCLC) and extensive-stage small cell lung cancer (SCLC). The decision to use immunotherapy and the specific regimen chosen are highly individualized, depending on several factors. A significant consideration is biomarker testing, which helps predict how likely a patient is to respond to immunotherapy.
Tests for PD-L1 expression on tumor cells are commonly performed. Higher levels of PD-L1 on cancer cells often correlate with a greater likelihood of response to PD-1/PD-L1 inhibitors. However, immunotherapy can still be effective even with lower PD-L1 levels. Another biomarker under investigation is tumor mutational burden (TMB), which refers to the total number of mutations within a tumor’s DNA. A higher TMB may also suggest a better response to immunotherapy.
Immunotherapy can be used as an initial treatment for Stage 4 lung cancer. It may also be administered after chemotherapy, or in combination with chemotherapy or targeted therapies. For instance, some regimens combine a PD-1 inhibitor with platinum-based chemotherapy. The goal is to maximize the anti-tumor effect while managing potential side effects. These personalized treatment strategies aim to offer the best possible outcomes for patients facing advanced lung cancer.