What is the information on Ipilimumab (Yervoy) and Nivolumab (Opdivo)?

From the Guidelines

Yervoy (ipilimumab) and Opdivo (nivolumab) are immunotherapy medications used primarily to treat various types of cancer, with the combination of nivolumab plus ipilimumab being a recommended option for first-line or second- or subsequent-line systemic therapy for unresectable or distant metastatic disease, based on the results from Checkmate-067 and Checkmate-069 1. These drugs work as immune checkpoint inhibitors, helping the body's immune system recognize and attack cancer cells. Yervoy targets a protein called CTLA-4, while Opdivo blocks PD-1 receptors. They are often used in combination therapy for advanced melanoma, renal cell carcinoma, colorectal cancer, and certain lung cancers, as this dual approach can be more effective than either drug alone. Some key points to consider when using these medications include:

• Typical combination dosing involves Opdivo at 3 mg/kg every 2 weeks with Yervoy at 1 mg/kg every 6 weeks, though regimens vary by cancer type.
• Common side effects include fatigue, rash, diarrhea, and nausea, but more serious immune-related adverse effects can occur, affecting organs like the lungs, liver, intestines, or endocrine system.
• Patients receiving these medications require regular monitoring through blood tests and clinical evaluations.
• Treatment duration depends on the specific cancer type and individual response, often continuing until disease progression or unacceptable toxicity occurs.
• The combination of nivolumab plus ipilimumab has been shown to have a high response rate and long duration of response, but also has a higher rate of grade 3-4 treatment-related adverse events compared to single-agent nivolumab or pembrolizumab 1.
• Recent guidelines suggest that nivolumab plus ipilimumab, nivolumab plus relatlimab, single-agent nivolumab, and single-agent pembrolizumab are all reasonable options for therapy in patients with BRAF wild-type unresectable or metastatic melanoma, with the choice of therapy depending on individual patient factors and preferences 1.

From the FDA Drug Label

YERVOY, as a single agent or in combination with nivolumab, is indicated for the treatment of unresectable or metastatic melanoma in adult and pediatric patients 12 years and older. YERVOY, in combination with nivolumab, is indicated for the first-line treatment of adult patients with intermediate or poor risk advanced renal cell carcinoma (RCC). YERVOY, in combination with nivolumab, is indicated for the treatment of adult and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. YERVOY, in combination with nivolumab, is indicated for the treatment of adult patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. YERVOY, in combination with nivolumab, is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test. YERVOY, in combination with nivolumab and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent NSCLC, with no EGFR or ALK genomic tumor aberrations. YERVOY, in combination with nivolumab, is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma. YERVOY, in combination with nivolumab, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).

Yervoy and Opdivo are used in combination for the treatment of various types of cancer, including:

• Melanoma: unresectable or metastatic melanoma in adult and pediatric patients 12 years and older
• Renal cell carcinoma: first-line treatment of adult patients with intermediate or poor risk advanced renal cell carcinoma
• Colorectal cancer: treatment of adult and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer
• Hepatocellular carcinoma: treatment of adult patients with hepatocellular carcinoma who have been previously treated with sorafenib
• Non-small cell lung cancer: first-line treatment of adult patients with metastatic non-small cell lung cancer whose tumors express PD-L1 (≥1%)
• Malignant pleural mesothelioma: first-line treatment of adult patients with unresectable malignant pleural mesothelioma
• Esophageal cancer: first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC) 2

From the Research

Yervoy and Opdivo Overview

• Yervoy (ipilimumab) and Opdivo (nivolumab) are immune checkpoint inhibitors used in combination to treat various types of cancer, including melanoma and non-small cell lung cancer (NSCLC) 3, 4, 5, 6, 7.
• The combination of Yervoy and Opdivo has shown durable and long-term efficacy in patients with advanced NSCLC and tumor PD-L1 expression greater than 1% or less than 1% 3.

Efficacy in Melanoma

• In patients with melanoma brain metastases, the combination of Yervoy and Opdivo has demonstrated a 7-year overall survival rate of 48% compared to 26% with Opdivo alone 7.
• The combination therapy has also shown improved intracranial progression-free survival and overall survival rates compared to Opdivo monotherapy in patients with melanoma brain metastases 7.

Efficacy in NSCLC

• A meta-analysis of randomized controlled trials found that the combination of Yervoy and Opdivo improved progression-free survival in patients with NSCLC compared to Opdivo monotherapy, but was associated with a greater risk of adverse events 4.
• The combination therapy has also shown durable and long-term efficacy in patients with advanced NSCLC and tumor PD-L1 expression greater than 1% or less than 1% 3.

Safety and Tolerability

• The combination of Yervoy and Opdivo has been associated with a higher risk of grade 3-4 adverse events compared to Opdivo monotherapy 4, 7.
• However, the safety results have been consistent with previous analyses, and the combination therapy has been shown to be effective and tolerable in patients with melanoma brain metastases 7.