Low-dose adjuvant ipilimumab improves OS in high-risk melanoma
Adjuvant treatment with ipilimumab significantly improved overall survival (OS) among patients with resected high-risk melanoma compared with high-dose interferon-α2b (HDI*), according to final results of the North American Intergroup E1609** trial presented at ASCO 2019.
“For the first time in the history of melanoma adjuvant therapy, E1609 has demonstrated a significant improvement in the primary endpoint of OS [with ipilimumab 3 mg/kg] against an active control regimen [with HDI, which was] previously shown to have both OS and [relapse-free survival (RFS)] benefits,” said study lead author Dr Ahmad Tarhini from the Department of Hematology and Medical Oncology at Emory University School of Medicine and Winship Cancer Institute of Emory University in Atlanta, Georgia, US.
This phase III trial evaluated patients with resected melanoma (stages IIIB, IIIC, M1a, or M1b) who were randomly assigned to receive adjuvant ipilimumab 3 mg/kg (n=523) or 10 mg/kg (n=511) intravenously Q3W for four cycles (induction phase) followed by every 3 months for four cycles (maintenance phase), or HDI (n=636) intravenously for 4 weeks (induction phase) followed by subcutaneously for up to 48 weeks (maintenance phase). [ASCO 2019, abstract 9504]
In the first-step analysis (ipilimumab 3 mg/kg vs HDI), patients treated with ipilimumab 3 mg/kg had a significantly higher OS rate compared with HDI at 5 years (0.72 percent vs 0.67 percent, hazard ratio [HR], 0.78, 95 percent confidence interval [CI], 0.61–0.99; log-rank p=0.044).
A longer RFS was observed among patients on ipilimumab 3 mg/kg than those on HDI (median, 4.5 vs 2.5 years, HR, 0.85, 95 percent CI, 0.66–1.09; log-rank p=0.065), although this was not statistically significant.
In the second-step analysis (ipilimumab 10 mg/kg vs HDI), those who received ipilimumab 10 mg/kg vs HDI demonstrated a better OS rate at 5-years (0.72 percent vs 0.65 percent, HR, 0.88, 95 percent CI, 0.69–1.12) and longer RFS (median, 3.9 vs 2.4 years, HR, 0.84, 95 percent CI, 0.65–1.09), but these findings did not reach statistical significance.
More patients who received ipilimumab 3 mg/kg completed the entire regimen than those who received ipilimumab 10 mg/kg (38.4 percent vs 21.5 percent).
Treatment-related adverse events (AEs) occurred at a lower rate in the ipilimumab 3 mg/kg vs 10 mg/kg arm (34.9 percent vs 54.1 percent), with all treatment-related AEs leading to treatment discontinuation. Grade 3 or 4 AEs were also less frequent in the ipilimumab 3 mg/kg arm compared with the ipilimumab 10 mg/kg arm (38.2 percent vs 56.7 percent).
“Adjuvant ipilimumab 3 mg/kg is significantly less toxic than ipilimumab 10 mg/kg and at least as effective in terms of RFS and OS outcomes,” Tarhini said.
“The data support the use of ipilimumab 3 mg/kg over HDI based on improved survival and similar RFS, and comparable toxicity. In cases where adjuvant therapy with ipilimumab represents an option, ipilimumab 3 mg/kg has an advantage over [the] approved dosage of ipilimumab 10 mg/kg,” he added.
*HDI: Dosage as per the standard FDA-approved regimen**E1609: A phase III randomized study of adjuvant ipilimumab (3 or 10 mg/kg) versus high-dose interferon-α2b for resected high-risk melanoma