Clinical experience with ipilimumab 3mg/kg: real-world efficacy and safety data from an expanded access programme cohort.

Paolo A Ascierto ,Lorenza Di Guardo,Carolina Cimminiello,Michele Guida,Ester Simeone,Paolo Marchetti,Jacopo Pigozzo,Francesco Cognetti,Maresa Altomonte,Riccardo Marconcini,Massimo Aglietta,Mario Mandalà,Michele Maio,Paola Queirolo,Gaetana Rinaldi,Ruggero Ridolfi,Michele Del Vecchio,Alessandro Testori,Vanna Chiarion-Sileni ,Maria Grazia Bernengo

doi:10.1186/1479-5876-12-116

Abstract

BackgroundIpilimumab improves survival in patients with advanced melanoma. The activity and safety of ipilimumab outside of a clinical trial was assessed in an expanded access programme (EAP).MethodsIpilimumab was available upon physician request for patients aged 16 or over with pretreated stage III (unresectable)/IV melanoma, for whom no other therapeutic option was available. Patients received ipilimumab 3 mg/kg every 3 weeks for four doses. Patients with stable disease or an objective response to ipilimumab were eligible for retreatment upon disease progression. Tumour assessments were conducted at baseline and week 12. Patients were monitored for adverse events (AEs) within 3 to 4 days of each scheduled visit.ResultsOf 855 patients participating in the EAP in Italy, 833 were evaluable for response. Of these, 13% had an objective immune response, and the immune-related disease control rate was 34%. Median progression-free survival and overall survival were 3.7 and 7.2 months, respectively. Efficacy was independent of BRAF and NRAS mutational status. Overall, 33% of patients reported an immune-related AE (irAE). The frequency of irAEs was not associated with response to ipilimumab.ConclusionsOutside of a clinical trial setting, ipilimumab is a feasible treatment option in patients with pretreated metastatic melanoma, regardless of BRAF and NRAS mutational status. Data from this large cohort of patients support clinical trial evidence that ipilimumab can induce durable disease control and long-term survival in patients who have failed to respond to prior treatment.

Highlights

Ipilimumab is a monoclonal antibody that blocks cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), a negative regulator of T-cell activation, thereby augmenting proliferation and infiltration into tumours, leading to tumour cell death [1]
We describe the safety and efficacy of ipilimumab 3 mg/kg in patients enrolled in an expanded access programme (EAP) in Italy
Patients Between June 2010 and January 2012, 855 patients with cutaneous (n = 631), mucosal (n = 71), and ocular (n = 83) melanoma were treated with ipilimumab 3 mg/kg at one of 55 Italian centres in the EAP

Summary

Introduction

Ipilimumab is a monoclonal antibody that blocks cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), a negative regulator of T-cell activation, thereby augmenting proliferation and infiltration into tumours, leading to tumour cell death [1]. Mutations in the genes encoding the protein kinases BRAF and NRAS are found in around 40% to 50%, and 20% of patients with cutaneous melanoma, respectively [8,9,10]. Agents approved to treat these subpopulations include the BRAF inhibitors vemurafenib and dabrafenib, and the MEK inhibitor trametinib, which are indicated for adult patients with BRAFV600 mutation-positive advanced melanoma [11,12,13]. Other inhibitors of mutated MEK and/or NRAS are in advanced clinical development [14]. Responses to these agents may be short-lived due to the development of resistance and there is still a need to explore new therapeutic options [8]. The activity and safety of ipilimumab outside of a clinical trial was assessed in an expanded access programme (EAP)

Methods

Results

Conclusion