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Adjuvant GM-CSF, peptide vaccination fail to improve survival for advanced melanoma
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Neither a peptide vaccination nor granulocyte-macrophage colony–stimulating factor improved RFS or OS in patients with locally advanced or stage IV melanoma following surgery, according to results from a phase 3 trial of the Eastern Cooperative Oncology Group.
However, results showed GM-CSF may benefit patients with resected visceral metastases.
Early clinical trial data of GM-CSF — a well-tolerated cytokine that increases the number of monocytes/macrophages in patients with cancer — demonstrated benefit as adjuvant therapy for melanoma.
David H. Lawson, MD, professor in the department of hematology and medical oncology at Emory University School of Medicine and a member of the Eastern Cooperative Oncology Group melanoma committee, and colleagues conducted this phase 3 trial to evaluate the effect of GM-CSF and a peptide vaccine on RFS and OS in high-risk patients with completely resected stage III to IV melanoma.
Researchers stratified patients according to HLA-A2 status. HLA-A2–positive patients received GM-CSF, peptide vaccination, both or placebo. HLA-A2–negative patients received GM-CSF or placebo.
A comparison of survival outcomes between GM-CSF and placebo served as the primary outcome. RFS in HLA-A2–positive patients treated with a peptide vaccine vs. placebo served as a secondary outcome.
The investigators enrolled 815 patients between 1999 and 2006. Overall, 53.5% of the patients were HLA-A2–positive.
Researchers observed no significant improvements in OS (HR = 0.94; 95% CI, 0.77-1.15) or RFS (HR = 0.88; 95% CI, 0.74-1.04) among patients assigned GM-CSF (n = 408) compared with patients assigned placebo (n = 407).
Median OS was 69.6 months (95% CI, 53.4-83.5) for the GM-CSF arm compared with 59.3 months (95% CI, 44.4-77.3) in the placebo arm.
Median RFS was 11.4 months (95% CI, 9.4-14.8) with GM-CSF compared with 8.8 months (95% CI, 7.5-11.2) with placebo.
“These results are not statistically significant but leave open the question whether GM-CSF may have smaller benefits,” Lawson and colleagues wrote.
The probability rates for 5-year OS were 52.3% (95% CI, 47.3-57.1) for GM-CSF compared with 49.4% (95% CI, 44.3-54.3) for placebo. The probability rates of 5-year RFS were 31.2% (95% CI, 26.7-35.9) for GM-CSF compared with 27% (95% CI, 22.7-31.5) for placebo.
The researchers identified a trend toward improved OS for GM-CSF–treated patients with resected stage M1b or M1c tumors, or those with visceral metastases (median OS, 72.4 months vs. 37.3 months; P ˂ .001).
OS and RFS did not significantly differ among HLA-A2–positive patients who received a peptide vaccine compared with placebo.
Incidence of treatment-related grade 3 or worse adverse events appeared similar among patients who received GM-CSF vs. placebo and peptide vaccine vs. placebo.
“Although this study did not support the hypothesis that adjuvant GM-CSF could make a significant impact on RFS or OS of the study population, trials that test GM-CSF in patients with resected visceral melanoma metastases are worthy of consideration,” the researchers wrote.
Researchers suggested that patients who may not be able to tolerate or who may be unwilling to use current immunotherapeutic agents in an adjuvant setting because of a borderline performance status or other comorbidities may be the ideal population for such studies.
“GM-CSF may find its greatest use in melanoma in combination with other agents,” they concluded. – by Anthony SanFilippo
Disclosure: Lawson reports honoraria, research funding, and travel accommodations and expenses from Amgen, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Merck and Prometheus Laboratories. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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