Adjuvant nivolumab is a type of immunotherapy used in cancer treatment. Immunotherapy works by harnessing the body’s own immune system to fight cancer cells. Adjuvant therapy refers to additional treatment given after the primary treatment, such as surgery, has removed the visible tumor. The purpose of adjuvant therapy is to reduce the chance of the cancer returning by targeting any remaining cancer cells that might not have been removed by the initial treatment.
Understanding How Nivolumab Works
Nivolumab functions as a programmed death-1 (PD-1) inhibitor, a type of immune checkpoint inhibitor. PD-1 is a protein on the surface of immune cells, specifically T cells. These T cells are white blood cells that help the body fight off diseases.
The PD-1 protein acts as an “immune checkpoint,” putting a brake on the immune system’s activity. Cancer cells can exploit this checkpoint by expressing PD-L1, which binds to PD-1 on T cells. This binding signals T cells to ignore the cancer cells, preventing the immune system from attacking them.
Nivolumab works by blocking the PD-1 protein on T cells. This prevents PD-L1 on cancer cells from binding to PD-1, effectively “releasing the brakes” on the immune system. This allows T cells to recognize and attack cancer cells more effectively, enhancing the body’s anti-tumor response.
Cancers Treated with Adjuvant Nivolumab
Adjuvant nivolumab is approved and commonly used for several types of cancer after primary treatment to lower the risk of recurrence. Its application varies based on the specific cancer type and disease stage.
Melanoma
Adjuvant nivolumab is approved for adult patients with Stage IIB, IIC, or III melanoma who have undergone complete surgical removal. This treatment reduces the risk of melanoma recurrence, especially when the cancer has spread to nearby lymph nodes or has high-risk features. The approval for adjuvant nivolumab in this setting was supported by studies such as the CheckMate-238 trial, which demonstrated improved recurrence-free survival compared to other treatments.
Esophageal or Gastroesophageal Junction (GEJ) Cancer
Nivolumab is used as adjuvant therapy for patients with resected esophageal or GEJ cancer who have residual pathological disease after receiving neoadjuvant chemoradiotherapy and surgery. The CheckMate-577 trial showed that adjuvant nivolumab significantly improved disease-free survival in these patients, effectively doubling the median disease-free survival from about 11 months to 22.4 months compared to placebo. This treatment is relevant for patients who did not achieve a complete pathological response to initial chemoradiotherapy.
Urothelial Carcinoma
Adjuvant nivolumab is indicated for patients with high-risk muscle-invasive urothelial carcinoma (MIUC), including bladder cancer and upper tract urothelial carcinoma, after radical resection. The CheckMate-274 trial demonstrated a significant benefit in disease-free survival with nivolumab compared to placebo in both the overall patient population and those with PD-L1 expression of 1% or greater. This treatment helps reduce the likelihood of cancer returning in patients who have undergone surgery for invasive disease.
Non-Small Cell Lung Cancer (NSCLC)
Nivolumab is used in the perioperative setting for resectable NSCLC. It is approved in combination with platinum-doublet chemotherapy as neoadjuvant treatment, followed by single-agent nivolumab as adjuvant treatment for adults with resectable NSCLC without certain genetic mutations. The CheckMate-77T trial showed that this perioperative approach significantly improved event-free survival compared to chemotherapy alone, with a median event-free survival that was not reached in the nivolumab arm versus 18.4 months in the chemotherapy arm.
What to Expect During Adjuvant Nivolumab Treatment
Adjuvant nivolumab is administered intravenously, directly into a vein through an infusion. Frequency of administration varies, typically every 2 or 4 weeks, and treatment can last up to one year, depending on the cancer type and patient response. This treatment is given in a hospital or clinic setting.
Patients undergoing nivolumab treatment may experience immune-related adverse events (irAEs). These side effects occur because the immune system becomes more active and can sometimes target healthy tissues in addition to cancer cells. Common irAEs include fatigue, skin rash, and diarrhea.
Other potential side effects involve various organ systems, such as inflammation of the thyroid gland (thyroid issues), lungs (pneumonitis), colon (colitis), or liver (hepatitis). Patients might also experience muscle or joint pain, or changes in kidney function. It is important for patients to promptly report any new or worsening symptoms to their healthcare team.
Managing these side effects often involves temporary cessation of nivolumab treatment and the administration of medications like corticosteroids to suppress the overactive immune response. Regular blood tests and clinical assessments are conducted throughout the treatment period to monitor for side effects and evaluate the patient’s response to the therapy. This close monitoring helps ensure that any potential issues are addressed quickly.