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Biomarker May Predict Response to Ipilimumab in Advanced Melanoma

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Key Points

  • At 24 weeks after starting ipilimumab, 41% of patients with late-stage melanoma and low levels of VEGF experienced clinical benefit vs 23% of patients with higher levels of VEGF.
  • The median overall survival for VEGF-low patients was 12.9 months, compared with 6.6 months for VEGF-high patients.
  • The findings suggest that there is a potential interaction between the biology of angiogenesis and immune-checkpoint blockade.

Among patients with advanced melanoma, presence of higher levels of the protein vascular endothelial growth factor (VEGF) in blood was associated with poor response to treatment with the immunotherapy ipilimumab (Yervoy), according to a study by Yuan et al published in Cancer Immunology Research. The study suggests combining immunotherapy with VEGF inhibitors may be a potential option for these patients.

The immune-checkpoint inhibitor ipilimumab works by boosting the body’s immune system to combat melanoma. VEGF is a protein that promotes angiogenesis, thus providing nutrients to the growing tumor. The study found that among patients who had late-stage melanoma, those who had high levels of VEGF in their blood prior to treatment with ipilimumab had decreased clinical benefit, poor overall survival outcomes, and were 60% more likely to die of their disease, compared with those who had lower levels of VEGF.

“VEGF is known to suppress the maturation of immune cells and their antitumor responses, and evidence points toward an association between high serum VEGF levels and poor prognosis in melanoma patients,” said F. Stephen Hodi, MD, Director of the Melanoma Center at Dana-Farber Cancer Institute. “VEGF has also been shown to be a potential biomarker for other immunotherapies; thus, it seemed logical to test the ability of VEGF to predict responses to ipilimumab.”

According to Dr. Hodi, VEGF may hinder some of the effects of the immune-checkpoint inhibitor. “We are beginning to better define predictive biomarkers for immune-checkpoint blockers, specifically ipilimumab. Our study further suggests that there is a potential interaction existing between the biology of angiogenesis and immune-checkpoint blockade,” he said.

Study Details

The investigators conducted retrospective analyses of blood samples collected from 176 patients with metastatic melanoma, before and after they were treated with ipilimumab, at Dana-Farber/Harvard Cancer Center and Memorial Sloan Kettering Cancer Center. Patients were 16 to 91 years old, and the majority of them had stage IV disease.

VEGF levels in patients’ blood ranged from 0.1 to 894.4 pg/mL. The investigators determined 43 pg/mL to be the cutoff value, and evaluated patient responses to treatment as those whose pretreatment VEGF levels were greater than (VEGF-high) or less than (VEGF-low) the cutoff value.

Outcomes

The investigators found that at 24 weeks after starting ipilimumab treatment, 41% of the VEGF-low patients experienced clinical benefit, including partial or complete treatment responses; only 23% of the VEGF-high patients experienced a clinical benefit.

The median overall survival for VEGF-low patients was 12.9 months, compared with 6.6 months for VEGF-high patients.

The researchers found that while pretreatment VEGF levels had the potential to predict treatment outcomes, changes in VEGF levels during treatment were not linked to treatment outcomes.

“It may be worthwhile to investigate combining immune-checkpoint inhibitors and angiogenesis inhibitors in advanced melanoma with high serum VEGF levels,” said Dr. Hodi. His team has initiated a randomized clinical trial to test ipilimumab in combination with bevacizumab (Avastin), an angiogenesis inhibitor, in patients with advanced melanoma.

Dr. Hodi is the corresponding author for the Cancer Immunology Research article.

This study was funded by the National Institutes of Health.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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