Nivolumab is a type of immunotherapy that has emerged as a treatment option for certain cancers, including bladder cancer. This medication works by engaging the body’s own immune system to target and fight cancer cells. This article explores how nivolumab functions, when it is used for bladder cancer, and what patients might experience during treatment.
Understanding How Nivolumab Works
Nivolumab is classified as an immune checkpoint inhibitor, targeting the programmed death-1 (PD-1) receptor. This receptor is found on the surface of T cells, a type of white blood cell that identifies and destroys abnormal cells, including cancer cells. Under normal circumstances, the PD-1 pathway helps prevent the immune system from overreacting and attacking healthy tissues.
Cancer cells exploit this natural mechanism by expressing ligands like PD-L1 and PD-L2 on their surface. When these ligands bind to the PD-1 receptor on T cells, they send an inhibitory signal, “turning off” the T cells, allowing cancer cells to evade immune detection and destruction. Nivolumab intervenes by binding to the PD-1 receptor itself, blocking the interaction between PD-1 and its ligands. This blockade lifts the inhibitory signal, thereby reactivating the T cells.
With the inhibitory signal removed, T cells can regain their ability to recognize and attack cancer cells more effectively. This process allows the immune system to mount a stronger and more sustained anti-tumor response. Nivolumab “releases the brakes” on the immune system, enabling it to function more effectively against various cancers, including urothelial carcinoma, the most common type of bladder cancer.
When Nivolumab is Used for Bladder Cancer
Nivolumab (Opdivo) is approved by the U.S. Food and Drug Administration (FDA) for specific types of bladder cancer. It is indicated for patients with locally advanced or metastatic urothelial carcinoma. This includes individuals whose disease has progressed during or following platinum-containing chemotherapy. It is also approved for patients who experienced disease progression within 12 months of receiving platinum-containing chemotherapy as neoadjuvant (before surgery) or adjuvant (after surgery) treatment.
Nivolumab also has FDA approval for the adjuvant treatment of patients with urothelial carcinoma at high risk of recurrence after radical resection, regardless of prior neoadjuvant chemotherapy, nodal involvement, or PD-L1 status. More recently, in March 2024, nivolumab received approval for first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma when used in combination with cisplatin and gemcitabine chemotherapy.
Nivolumab is administered intravenously. The frequency of treatment varies depending on the specific indication and whether it is used as a single agent or in combination with other therapies. For adjuvant treatment of urothelial carcinoma, a typical dosage is 240 mg every 2 weeks or 480 mg every 4 weeks. When used in combination with chemotherapy for first-line treatment, a common regimen is 360 mg every 3 weeks for up to six cycles, followed by single-agent nivolumab at 240 mg every 2 weeks or 480 mg every 4 weeks until disease progression, unacceptable toxicity, or a maximum of two years from the first dose.
Patient Experience and Managing Treatment
Patients undergoing nivolumab treatment may experience various side effects. These are referred to as immune-related adverse events (irAEs). Common irAEs include fatigue, skin rash, and diarrhea. Other potential side effects involve the endocrine system, including thyroid issues like hypothyroidism or hyperthyroidism.
More serious irAEs can affect various organs. These may include pneumonitis (inflammation of the lungs), colitis (inflammation of the colon), hepatitis (inflammation of the liver), and nephritis (inflammation of the kidneys). Patients might also experience endocrinopathies or musculoskeletal pain. Adrenal insufficiency and autoimmune diabetes mellitus are rarer but possible.
Medical teams monitor patients for these side effects. Management involves corticosteroids to suppress the immune response and alleviate symptoms. A maculopapular rash, a type of skin reaction, has been observed in approximately 13% to 16% of nivolumab users. The goal of treatment is to control the disease. For patients with high-risk urothelial carcinoma, adjuvant nivolumab has been shown to reduce the risk of disease recurrence or death.