The combination of the anti-PD-1 molecule pembrolizumab and low-dose ipilimumab (CTLA-4 blockade) showed significant antitumour activity among patients with advanced melanoma who previously failed prior immunotherapy, reveals a new study in Journal of Cinical Oncology.
“Front-line pembrolizumab plus ipilimumab has an incrementally higher response rate than anti-PD-1 alone in patients with melanoma but with severe immune-related toxicity in more than 50% of patients,” said Dr. Jason J. Luke, Director of the Cancer Immunotherapeutics Center and associate professor of medicine at UPMC Hillman Cancer Center and University of Pittsburgh School of Medicine, in a statement.
Ipilimumab in the second-line setting is associated historically with a 13% response rate, although previous studies have suggested an ability of the drug to drive new T cells into the tumour microenvironment.
Dr. Luke and colleagues evaluated the efficacy and safety of 1 mg/kg ipilimumab plus 200 mg pembrolizumab once every 3 weeks for four doses, followed by 200 mg pembrolizumab alone every 3 weeks for up to 2 years, among 70 patients with advanced melanoma who had progressed on immediate prior therapy with an anti-PD-1 antibody alone (n = 60) or anti-PD-1/L1 antibody-based combinations (n = 10).
About 89% had cutaneous melanoma, 29% had BRAF V600 mutations, 49% had M1c or M1d disease and 31% had elevated serum lactate dehydrogenase concentrations. About 76% of patients received four or more doses of pembrolizumab plus low-dose ipilimumab. The other patients received a median two cycles of therapy.
Results showed an overall response rate of 29%, including five (7.2%) complete responses and 15 (21.4%) partial responses.
“These data, in conjunction with the international retrospective study on the same topic, suggest that an anti-CTLA-4 antibody should no longer be given as a monotherapy but rather combined with anti-PD-1 antibody and given as a low dose as a second-line treatment for melanoma,” Dr Luke said.
“Anti-PD-1 antibody with low-dose ipilimumab is now considered a backbone regimen from which to develop combination regimens. We are now investigating the combination of BRAF with and without MEK inhibitors in combination with anti-PD-1 therapy and low-dose ipilimumab for extremely high-risk patients with advanced BRAF-mutant melanoma.” he added.
“Nonetheless, this study provides compelling evidence that the combination of PD-1 and CTLA-4 blockade is a safe and effective treatment approach in the PD-1-refractory patient population,” the authors wrote.