Renal cell carcinoma (RCC) is a common type of kidney cancer in adults, originating in the tiny tubes within the kidney. Following primary treatments, typically surgery, adjuvant therapy is often employed to help prevent the cancer from returning. Pembrolizumab is a notable therapy used in this adjuvant setting for certain individuals with RCC.
Understanding Renal Cell Carcinoma and Adjuvant Treatment
Renal cell carcinoma (RCC) is the most prevalent form of kidney cancer, with clear cell renal cell carcinoma (ccRCC) being its most common subtype, accounting for approximately 70% to 85% of cases. This cancer develops in the small tubules of the kidneys, which are essential for filtering blood and producing urine. While RCC usually manifests as a single tumor, some individuals may develop multiple tumors or have the disease affect both kidneys.
Surgery, specifically the removal of the affected kidney (nephrectomy), is a common primary treatment for localized RCC. Even when all visible cancer is successfully removed, microscopic cancer cells may remain, undetectable by current imaging methods. These lingering cells pose a risk for the cancer to recur.
Adjuvant therapy is an additional treatment administered after initial primary therapy, such as surgery. Its objective is to eradicate these microscopic cancer cells and reduce the likelihood of the cancer returning. This preventative measure aims to improve long-term outcomes. Adjuvant therapies can encompass various treatments, including chemotherapy, radiation, targeted therapy, and immunotherapy.
Pembrolizumab’s Mechanism of Action
Pembrolizumab is a type of immunotherapy, specifically a monoclonal antibody, known as an immune checkpoint inhibitor. Its function involves interacting with the body’s immune system to enhance its ability to fight cancer. The drug targets a specific protein called programmed cell death-1 (PD-1), which is found on the surface of immune cells known as T-cells.
Normally, PD-1 acts as a regulatory switch on T-cells. When PD-1 binds to another protein called PD-L1 (or PD-L2), which can be present on cancer cells, it sends an “off” signal to the T-cell, effectively preventing it from recognizing and attacking the cancer. Cancer cells often exploit this pathway to evade detection and destruction by the immune system.
Pembrolizumab works by blocking this interaction. It binds to the PD-1 protein on T-cells, preventing PD-L1 on cancer cells from attaching to it. This action essentially “unblocks” the T-cells, allowing them to remain active and recognize the cancer cells as foreign threats. By disrupting this immune checkpoint, pembrolizumab helps to restore the immune system’s natural capacity to identify and eliminate tumor cells.
What to Expect with Adjuvant Pembrolizumab
The use of adjuvant pembrolizumab for renal cell carcinoma is supported by clinical evidence, particularly from the KEYNOTE-564 trial. This study demonstrated that pembrolizumab significantly improved disease-free survival (the time a person lives without the cancer returning) and, with longer follow-up, overall survival in patients with clear cell RCC who had a higher risk of recurrence after kidney removal surgery. Based on these findings, pembrolizumab received approval in 2021 for this adjuvant treatment setting.
The treatment is administered intravenously (into a vein) and typically involves a dose of 200 mg every three weeks, or 400 mg every six weeks. The treatment course usually continues for up to one year, or approximately 17 cycles, unless disease recurrence or unacceptable side effects occur.
Individuals receiving pembrolizumab may experience various side effects, many of which are related to the immune system becoming more active. These are known as immune-related adverse events and can differ from the side effects commonly associated with traditional chemotherapy. Common side effects include fatigue, skin rash, and diarrhea.
More serious immune-related adverse events can affect different organ systems. These may include inflammation of the lungs (pneumonitis), intestines (colitis), liver (hepatitis), or kidneys (nephritis). Hormone glands, such as the thyroid, pituitary, and adrenal glands, can also be affected, potentially leading to conditions like hypothyroidism or adrenal insufficiency. These more significant side effects can be severe and may require immediate medical attention, sometimes even after treatment has concluded.
Careful monitoring is a component of treatment with adjuvant pembrolizumab to identify and manage any potential side effects. Healthcare providers will regularly evaluate liver enzyme levels, kidney function (creatinine), and thyroid hormone levels through blood tests. Prompt management, which may involve the use of corticosteroids, is often necessary to control immune-related adverse events. Patients are typically eligible for this treatment if they have histologically confirmed clear cell RCC with intermediate-high or high risk of recurrence following nephrectomy, or after nephrectomy and complete removal of metastatic lesions. Treatment initiation usually occurs within 12 weeks of the complete surgical resection.