Pembrolizumab is an immunotherapy drug that harnesses the body’s immune system to fight cancer cells. When used as “adjuvant therapy,” it is administered after a primary treatment, such as surgery, to help reduce the risk of cancer returning. This approach aims to target any remaining cancer cells that might be too small to detect.
Understanding Pembrolizumab
Pembrolizumab, known as Keytruda, is a programmed cell death protein 1 (PD-1) blocking antibody. It functions as an immune checkpoint inhibitor, designed to overcome mechanisms cancer cells use to evade the immune system. Pembrolizumab targets the PD-1 protein on T-cells, preventing it from interacting with its ligand, PD-L1, which can be expressed by cancer cells.
This interaction between PD-1 and PD-L1 typically acts as an “off switch” for T-cells, preventing them from attacking healthy cells. Cancer cells exploit this pathway to hide from the immune system. Pembrolizumab blocks this inhibitory signal, allowing T-cells to reactivate and identify cancer cells as foreign invaders, leading to their destruction.
The Role of Adjuvant Therapy
Adjuvant therapy refers to additional cancer treatment given after the primary treatment, which often involves surgery to remove a tumor. Its main purpose is to eliminate any microscopic cancer cells that may have lingered in the body undetected. Even after a seemingly successful surgery, a small number of cancer cells can remain, potentially leading to a recurrence of the disease.
The goal of adjuvant therapy is to reduce the chance of the cancer coming back by targeting these residual cells before they can grow into new tumors. This preventative measure aims to improve long-term outcomes for patients. This approach recognizes that cancer can be a systemic disease, meaning cells might spread beyond the primary tumor site even if they are not yet visible.
How Adjuvant Pembrolizumab Works
Adjuvant pembrolizumab leverages the immune system to prevent cancer recurrence. After primary treatments like surgery, tiny clusters of cancer cells, known as micrometastases, may persist. These cells are often too small to be detected by imaging scans but have the potential to grow and cause the cancer to return.
The mechanism involves disrupting the PD-1/PD-L1 pathway, which cancer cells commonly use to suppress the immune response. By blocking PD-1 on T-cells, pembrolizumab prevents cancer cells that express PD-L1 from deactivating these immune cells. This allows T-cells to regain their ability to recognize and attack the microscopic cancer cells that remain after the initial tumor removal, thereby lowering the likelihood of disease recurrence.
Cancers Where Adjuvant Pembrolizumab is Used
Adjuvant pembrolizumab has gained approval for use in several types of cancer following primary treatment. One notable application is in certain stages of melanoma, a serious form of skin cancer. It is often used after surgical removal of stage IIB, IIC, or III melanoma.
The therapy is also approved for specific cases of non-small cell lung cancer (NSCLC), including patients with stage IB, II, or IIIA NSCLC who have undergone surgical resection and platinum-based chemotherapy. Additionally, it is utilized in certain patients with renal cell carcinoma after they have had surgery to remove the kidney or the cancerous part of it.
Managing Potential Side Effects
Adjuvant pembrolizumab works by activating the immune system, and its side effects are often described as immune-related adverse events (irAEs). These occur when the immune system attacks healthy tissues. Common irAEs include fatigue, skin rashes, and itching. More serious immune-related reactions can affect organs such as the colon (colitis), lungs (pneumonitis), liver (hepatitis), or endocrine glands like the thyroid or adrenal glands, leading to conditions like hypothyroidism or adrenal insufficiency.
Managing these side effects involves careful monitoring and prompt intervention. Patients are educated to recognize and report any new or worsening symptoms to their healthcare team immediately. Depending on the severity and type of irAE, treatment may involve temporary interruption or discontinuation of pembrolizumab. Corticosteroids are frequently used to suppress the immune response and manage inflammation in affected organs.