Effectiveness of Neoadjuvant Nivolumab and Ipilimumab in Resectable Stage III Melanoma
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Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by Nhi Phuong Quynh Le, B.A |
Posted on December 18th, 2024
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For patients with resectable melanoma, nivolumab, a PD-1 inhibitor, and ipilimumab, a CTLA-4 inhibitor, can be used as adjuvant treatments to eliminate residual tumor cells following surgery. Both nivolumab and ipilimumab function by blocking the signals tumor cells use to suppress immune cell activity. A study sponsored by Bristol Myers was conducted to assess whether administering nivolumab and ipilimumab as neoadjuvant therapy before surgery could also be effective.
The phase 3 clinical trial involved 423 participants with a median age of approximately 60 years, all diagnosed with resectable stage III cutaneous or acral melanoma. Ulceration was present in about 30% of the patients, and metastasis had occurred in 10% of participants. Genomic analyses revealed that 45% of patients had no BRAF mutation, less than 45% had a valine-to-glutamate (V600E) mutation at the 600th amino acid, approximately 10% had a valine-to-lysine (V600K) mutation, and the remaining patients had other forms of mutations. The participants were randomly assigned to receive either nivolumab and ipilimumab before surgery or after surgery. The neoadjuvant treatment consisted of two doses administered every 3 weeks, each containing 80 mg of ipilimumab and 240 mg of nivolumab. Patients in the traditional treatment group received 12 cycles of nivolumab alone every 4 weeks. The researchers found that neoadjuvant treatment with nivolumab and ipilimumab reduced the risk of death and disease progression by 68%, extending the average survival by 8 months compared to those receiving nivolumab after surgery. This improved clinical outcome was observed in both BRAF-mutant and BRAF-wild type patients. The researchers hypothesize that the enhanced effectiveness of neoadjuvant treatment may be due to the combination of PD-1 inhibition with ipilimumab or the presence of sufficient tumor antigens before surgery, allowing for a stronger immune response.
The phase 3 clinical trial involved 423 participants with a median age of approximately 60 years, all diagnosed with resectable stage III cutaneous or acral melanoma. Ulceration was present in about 30% of the patients, and metastasis had occurred in 10% of participants. Genomic analyses revealed that 45% of patients had no BRAF mutation, less than 45% had a valine-to-glutamate (V600E) mutation at the 600th amino acid, approximately 10% had a valine-to-lysine (V600K) mutation, and the remaining patients had other forms of mutations. The participants were randomly assigned to receive either nivolumab and ipilimumab before surgery or after surgery. The neoadjuvant treatment consisted of two doses administered every 3 weeks, each containing 80 mg of ipilimumab and 240 mg of nivolumab. Patients in the traditional treatment group received 12 cycles of nivolumab alone every 4 weeks. The researchers found that neoadjuvant treatment with nivolumab and ipilimumab reduced the risk of death and disease progression by 68%, extending the average survival by 8 months compared to those receiving nivolumab after surgery. This improved clinical outcome was observed in both BRAF-mutant and BRAF-wild type patients. The researchers hypothesize that the enhanced effectiveness of neoadjuvant treatment may be due to the combination of PD-1 inhibition with ipilimumab or the presence of sufficient tumor antigens before surgery, allowing for a stronger immune response.