Adjuvant therapy, administered after primary procedures like surgery, aims to prevent cancer recurrence by addressing microscopic cancer cells that might remain. This strategy is particularly relevant for conditions like renal cell carcinoma (RCC).
Understanding Renal Cell Carcinoma and Adjuvant Therapy
Renal cell carcinoma (RCC) is the most common type of kidney cancer, originating in the lining of the kidney tubules. While surgical removal of the tumor is often the primary treatment, some cancer cells might have spread beyond the kidney but are too small to be detected. This unseen presence can lead to disease recurrence, even years after successful surgery. Approximately 20% of patients who undergo surgery for localized RCC may experience a recurrence.
Adjuvant therapy is a treatment given after the main treatment, typically surgery, with the goal of preventing cancer from returning. Its purpose is to eliminate any residual cancer cells that might still be in the body. This type of therapy is distinct from treatments given before surgery, known as neoadjuvant therapy.
Pembrolizumab: How it Works
Pembrolizumab (Keytruda) is a type of immunotherapy. It harnesses the body’s immune system to identify and fight cancer cells. Unlike traditional chemotherapy, which directly attacks cancer cells, pembrolizumab works to empower the immune system’s T cells.
This medication is an immune checkpoint inhibitor, targeting the programmed cell death-1 (PD-1) receptor on T cells. Cancer cells can often evade immune detection by expressing proteins like PD-L1 and PD-L2, which bind to PD-1 on T cells, effectively “turning off” the immune response. Pembrolizumab blocks this interaction, preventing cancer cells from deactivating the T cells. This blockade releases the natural “brakes” on the immune system, allowing T cells to become active again and destroy cancer cells.
Receiving Adjuvant Pembrolizumab
Adjuvant pembrolizumab is indicated for specific patients with renal cell carcinoma who have undergone nephrectomy. Eligibility typically includes adults with clear cell RCC who are at intermediate-high or high risk of recurrence following nephrectomy, or after nephrectomy and complete removal of metastatic lesions. Risk factors considered include the tumor’s pathological stage, such as pT2 with Grade 4 or sarcomatoid features, pT3, pT4, or N1 disease, and M1 disease with no evidence of disease (M1 NED) after complete resection.
The medication is administered intravenously. The typical dosing schedule involves receiving 200 mg every three weeks or 400 mg every six weeks. Treatment is generally continued for up to one year, or until disease recurrence or unacceptable side effects occur. Regular monitoring by the healthcare team is an important part of the treatment process to assess how the patient is responding and to manage any potential issues.
Managing Treatment and Outcomes
Pembrolizumab, like other immunotherapies, can cause various side effects, ranging from common to more serious immune-related adverse events. Common side effects reported include fatigue, rash, diarrhea, itching, musculoskeletal pain, and hypothyroidism. These are managed with supportive care.
More significant side effects can arise when the immune system, activated by pembrolizumab, mistakenly attacks healthy organs and tissues. These immune-related adverse events may affect various systems, leading to conditions such as inflammation of the lungs (pneumonitis), colon (colitis), liver (hepatitis), kidneys (nephritis), or hormone glands (endocrinopathies). Close monitoring by the medical team is performed to detect these events early, and they are frequently managed with corticosteroids to reduce inflammation. Clinical trials, such as KEYNOTE-564, have demonstrated that adjuvant pembrolizumab significantly improves disease-free survival (DFS) and overall survival (OS) in eligible patients. In the KEYNOTE-564 trial, pembrolizumab showed a 32% reduction in the risk of recurrence or death compared to placebo. Additionally, a 38% reduction in the risk of death was observed, with the estimated overall survival rate at 48 months being 91.2% in the pembrolizumab group versus 86.0% in the placebo group. While these outcomes represent significant progress, individual responses can vary, emphasizing the importance of ongoing follow-up with the medical team.