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VEGF level may predict response to ipilimumab


FROM CANCER IMMUNOLOGY RESEARCH


Vitals

Major Finding: 41% of 90 patients with low serum VEGF showed clinical benefit with ipilimumab, compared with 23% of the 69 patients with a high VEGF level.

Data Source: A preliminary study involving 159 patients with advanced melanoma who received 12 weeks of ipilimumab therapy, of whom 33% showed clinical benefit ranging from disease stabilization to complete eradication of the tumor.

Disclosures: This study was supported by the National Institutes of Health. Four of Dr. Yuan’s associates reported receiving support from and serving as consultants for Bristol-Myers Squibb, which developed the monoclonal antibody ipilimumab.

Among patients with advanced melanoma who are being considered for ipilimumab therapy, serum vascular endothelial growth factor level may predict who will respond to the treatment and who will not, according to a report published online Feb. 4 in Cancer Immunology Research.

Only a subset of patients with advanced melanoma benefit from the CTLA-4 blocker ipilimumab, but those who do show marked and durable improvement, so there is "a critical need" to identify biomarkers that predict treatment response, said Dr. Jianda Yuan of the Ludwig Center for Cancer Immunotherapy, Sloan-Kettering Cancer Center, New York, and his associates.

The investigators assessed circulating vascular endothelial growth factor (VEGF) levels before and after ipilimumab therapy in 176 patients aged 16-91 years (mean age, 62) who were treated for advanced melanoma at Sloan-Kettering and at Dana-Farber/Harvard Cancer Center, Boston. A total of 78 patients received 10 mg/kg and 98 received 3 mg/kg every 3 weeks for 12 weeks. Those who showed clinical benefit and no dose-limiting toxicity at 24 weeks could continue receiving the drug until the disease progressed, they died, toxicity occurred, or they withdrew from the study.

One-third of the study participants (53 of the 159 patients evaluable at week 24) showed clinical benefit, including 3 complete responders, 13 partial responders, and 37 with stabilization of their disease, the investigators said (Cancer Immunol. Res 2014 Feb. 4 [doi:10.1158/2326-6066.CIR-13-0163]).

Patients with serum VEGF levels higher than 43 pg/mL were significantly less likely to respond to ipilimumab and had significantly shorter overall survival than those with lower levels, regardless of which dose of the drug they were given. Thirty-seven of the 90 patients with low VEGF (41%) showed clinical benefit with ipilimumab, compared with only 16 of the 69 patients with high VEGF (23%).

The findings of this preliminary research show that prospective studies are warranted to assess whether baseline serum VEGF can serve as a predictive biomarker, Dr. Yuan and his associates said.

This study was supported by the National Institutes of Health. Four of Dr. Yuan’s associates reported receiving support from and serving as consultants for Bristol-Myers Squibb, which developed the monoclonal antibody ipilimumab.