Yervoy Improves Survival in Stage 3 Melanoma

Adjuvant treatment with recombinant, human monoclonal antibody extended overall survival in patients with melanoma in a recent trial.

A recent study found that adjuvant treatment with Yervoy (ipilimumab) may improve survival in patients with stage 3 melanoma.

Results from the CA184-029 (EORTC 18071) phase 3 trial will be presented at the European Society of Medical Oncology Congress (ESMO).

Melanoma is the most serious and deadly form of skin cancer when it metastasizes to lymph nodes, lungs, brain, or other organs. In stage 3, the cancer has metastasized to the local lymph nodes, but has not spread to distant lymph nodes.

Surgical resection of the primary tumor and local lymph nodes is required for treatment, according to a press release from Bristol-Myers Squibb.

“Despite surgical intervention, most patients with stage III melanoma experience disease recurrence and progress to metastatic disease, reinforcing the unmet need for effective systemic therapies in the adjuvant setting,” said lead author Alexander M.M. Eggermont, MD, PhD. “The impact of Yervoy on overall survival, distant-metastasis free survival, and recurrence-free survival observed in study -029 offers physicians new insights in the treatment of adjuvant melanoma.”

Yervoy is a recombinant, human monoclonal antibody that binds with cytotoxic T-lymphocyte-associated antigen-4, which is a negative regulator of T cell activity, according to Bristol-Myers Squibb.

In the trial, researchers analyzed ipilimumab as an adjuvant treatment for 951 patients with high risk melanoma. Patients were randomized to receive Yervoy or a placebo for 3 years, or until they were disease-free or faced unacceptable toxicity, according to the press release.

It was previously announced that the trial met its primary endpoint, increasing recurrence-free survival, after a follow up of 2.3 years, and received FDA approval. Scientists found in the current follow up of 5.3 years that treatment with Yervoy decreased the relative risk of death among patients by 28%.

At 5 years, the overall survival rate was 11% higher among patients taking ipilimumab compared with those taking the placebo, according to the study. Immune-related adverse events are known to occur in those taking Yervoy. No additional deaths or toxicities were reported after 5 years.

Serious grade 3-4 adverse events included gastrointestinal, hepatic, and endocrine. Gastrointestinal and hepatic events were able to be resolved in 4 to 8 weeks, but endocrine adverse events typically took longer to resolve or required permanent hormonal replacement treatments, according to the study.

“Ipilimumab adjuvant therapy brings a significant improvement of overall survival and has a favorable risk-benefit ratio,” Dr Eggermont said. “It clearly represents a serious option for patients with stage III melanoma.”

Yervoy received FDA approval in 2011 for patients with unresectable or metastatic melanoma, and has received approval in more than 50 other countries. There is currently an ongoing development program investigating Yervoy in multiple other cancers, according to Bristol Myers-Squibb.

“The results from study -029 are important data for the scientific community and underscore our ongoing dedication to improving survival across stages of melanoma,” said Vicki Goodman, MD, development lead, Melanoma and Genitourinary Cancers, Bristol-Myers Squibb. “Yervoy is the first immune checkpoint inhibitor to demonstrate a statistically significant survival benefit for high-risk patients with fully resected stage III melanoma. With further evaluation of our Immuno-Oncology agents and different dosing options, we remain committed to further research across the full continuum of melanoma treatment.”