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Efficacy and toxicity of treatment with the anti-CTLA-4 antibody ipilimumab in patients with metastatic melanoma after prior anti-PD-1 therapy

S Bowyer, P Prithviraj, P Lorigan, J Larkin, G McArthur, V Atkinson, M Millward, M Khou, Stefan Diem, S Ramanujam, B Kong, E Liniker, A Guminski, P Parente, M C Andrews, S Parakh, J Cebon, G V Long, M S Carlino & O Klein

abstract

BACKGROUND
Recent phase III clinical trials have established the superiority of the anti-PD-1 antibodies pembrolizumab and nivolumab over the anti-CTLA-4 antibody ipilimumab in the first-line treatment of patients with advanced melanoma. Ipilimumab will be considered for second-line treatment after the failure of anti-PD-1 therapy.

METHODS
We retrospectively identified a cohort of 40 patients with metastatic melanoma who received single-agent anti-PD-1 therapy with pembrolizumab or nivolumab and were treated on progression with ipilimumab at a dose of 3 mg kg(-1) for a maximum of four doses.

RESULTS
Ten percent of patients achieved an objective response to ipilimumab, and an additional 8% experienced prolonged (>6 months) stable disease. Thirty-five percent of patients developed grade 3-5 immune-related toxicity associated with ipilimumab therapy. The most common high-grade immune-related toxicity was diarrhoea. Three patients (7%) developed grade 3-5 pneumonitis leading to death in one patient.

CONCLUSIONS
Ipilimumab therapy can induce responses in patients who fail the anti-PD-1 therapy with response rates comparable to previous reports. There appears to be an increased frequency of high-grade immune-related adverse events including pneumonitis that warrants close surveillance.
   
citation Bowyer S, Prithviraj P, Lorigan P, Larkin J, McArthur G, Atkinson V, Millward M, Khou M, Diem S, Ramanujam S, Kong B, Liniker E, Guminski A, Parente P, Andrews M C, Parakh S, Cebon J, Long G V, Carlino M S, Klein O. Efficacy and toxicity of treatment with the anti-CTLA-4 antibody ipilimumab in patients with metastatic melanoma after prior anti-PD-1 therapy. Br J Cancer 2016; 114:1084-9.
   
type journal paper/review (English)
date of publishing 28-04-2016
journal title Br J Cancer (114/10)
ISSN electronic 1532-1827
pages 1084-9
PubMed 27124339
DOI 10.1038/bjc.2016.107