Abstract
Background: Ipilimumab improves survival of patients with metastatic melanoma, many of whom develop brain metastases. Chemotherapy-induced release of tumour antigens might amplify ipilimumab's antitumour activity. We aimed to investigate the efficacy and safety of ipilimumab plus fotemustine in patients with metastatic melanoma with or without asymptomatic brain metastases. Methods: In our open-label, single-arm phase 2 trial, we enrolled patients 18 years or older with measurable, locally advanced, unresectable stage III or stage IV melanoma between July 6, 2010, and April 14, 2011. Eligible patients had a life expectancy of 16 weeks or more and an Eastern Cooperative Oncology Group performance status of 1 or less, and could have received a maximum of one previous line of chemotherapy. Participants received induction treatment of 10 mg/kg intravenous ipilimumab every 3 weeks to a total of four doses, and 100 mg/m 2 intravenous fotemustine weekly for 3 weeks and then every 3 weeks from week 9 to week 24. Patients with a confirmed clinical response were eligible for maintenance treatment from week 24, with ipilimumab every 12 weeks and fotemustine every 3 weeks. The primary endpoint was the proportion of patients with immune-related disease control as established with immune-related response criteria. Analyses were done per protocol. This trial is registered with EudraCT, number 2010-019356-50, and with ClinicalTrials.gov, number NCT01654692. Findings: 86 patients were eligible for treatment, of whom 20 had asymptomatic brain metastases at baseline. 40 patients in the study population achieved disease control (46·5%, 95% CI 35·7-57·6), as did ten with brain metastases (50·0%, 27·2-72·8). 47 patients (55%) had grade 3 or 4 treatment-related adverse events, of which the most common was myelotoxicity (thrombocytopenia in 21 [24%] patients and neutropenia in 16 [19%]). The most common grade 3 or 4 immune-related adverse events were hepatic: 21 patients (24%) had grade 3 or 4 increases in concentrations of alanine aminotransferase or aspartate aminotransferase. Interpretation: The combination of ipilimumab plus fotemustine has clinical activity in patients with metastatic melanoma, including those with brain metastases. Funding: Bristol-Myers Squibb.
| Original language | English |
|---|---|
| Pages (from-to) | 879-886 |
| Number of pages | 8 |
| Journal | The Lancet Oncology |
| Volume | 13 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - Sep 2012 |
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ASJC Scopus subject areas
- Oncology
Cite this
Ipilimumab and fotemustine in patients with advanced melanoma (NIBIT-M1) : An open-label, single-arm phase 2 trial. / Di Giacomo, Anna Maria; Ascierto, Paolo A.; Pilla, Lorenzo; Santinami, Mario; Ferrucci, Pier Francesco; Giannarelli, Diana; Marasco, Antonella; Rivoltini, Licia; Simeone, Ester; Nicoletti, Stefania V L; Fonsatti, Ester; Annesi, Diego; Queirolo, Paola; Testori, Alessandro; Ridolfi, Ruggero; Parmiani, Giorgio; Maio, Michele.
In: The Lancet Oncology, Vol. 13, No. 9, 09.2012, p. 879-886.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Ipilimumab and fotemustine in patients with advanced melanoma (NIBIT-M1)
T2 - An open-label, single-arm phase 2 trial
AU - Di Giacomo, Anna Maria
AU - Ascierto, Paolo A.
AU - Pilla, Lorenzo
AU - Santinami, Mario
AU - Ferrucci, Pier Francesco
AU - Giannarelli, Diana
AU - Marasco, Antonella
AU - Rivoltini, Licia
AU - Simeone, Ester
AU - Nicoletti, Stefania V L
AU - Fonsatti, Ester
AU - Annesi, Diego
AU - Queirolo, Paola
AU - Testori, Alessandro
AU - Ridolfi, Ruggero
AU - Parmiani, Giorgio
AU - Maio, Michele
PY - 2012/9
Y1 - 2012/9
N2 - Background: Ipilimumab improves survival of patients with metastatic melanoma, many of whom develop brain metastases. Chemotherapy-induced release of tumour antigens might amplify ipilimumab's antitumour activity. We aimed to investigate the efficacy and safety of ipilimumab plus fotemustine in patients with metastatic melanoma with or without asymptomatic brain metastases. Methods: In our open-label, single-arm phase 2 trial, we enrolled patients 18 years or older with measurable, locally advanced, unresectable stage III or stage IV melanoma between July 6, 2010, and April 14, 2011. Eligible patients had a life expectancy of 16 weeks or more and an Eastern Cooperative Oncology Group performance status of 1 or less, and could have received a maximum of one previous line of chemotherapy. Participants received induction treatment of 10 mg/kg intravenous ipilimumab every 3 weeks to a total of four doses, and 100 mg/m 2 intravenous fotemustine weekly for 3 weeks and then every 3 weeks from week 9 to week 24. Patients with a confirmed clinical response were eligible for maintenance treatment from week 24, with ipilimumab every 12 weeks and fotemustine every 3 weeks. The primary endpoint was the proportion of patients with immune-related disease control as established with immune-related response criteria. Analyses were done per protocol. This trial is registered with EudraCT, number 2010-019356-50, and with ClinicalTrials.gov, number NCT01654692. Findings: 86 patients were eligible for treatment, of whom 20 had asymptomatic brain metastases at baseline. 40 patients in the study population achieved disease control (46·5%, 95% CI 35·7-57·6), as did ten with brain metastases (50·0%, 27·2-72·8). 47 patients (55%) had grade 3 or 4 treatment-related adverse events, of which the most common was myelotoxicity (thrombocytopenia in 21 [24%] patients and neutropenia in 16 [19%]). The most common grade 3 or 4 immune-related adverse events were hepatic: 21 patients (24%) had grade 3 or 4 increases in concentrations of alanine aminotransferase or aspartate aminotransferase. Interpretation: The combination of ipilimumab plus fotemustine has clinical activity in patients with metastatic melanoma, including those with brain metastases. Funding: Bristol-Myers Squibb.
AB - Background: Ipilimumab improves survival of patients with metastatic melanoma, many of whom develop brain metastases. Chemotherapy-induced release of tumour antigens might amplify ipilimumab's antitumour activity. We aimed to investigate the efficacy and safety of ipilimumab plus fotemustine in patients with metastatic melanoma with or without asymptomatic brain metastases. Methods: In our open-label, single-arm phase 2 trial, we enrolled patients 18 years or older with measurable, locally advanced, unresectable stage III or stage IV melanoma between July 6, 2010, and April 14, 2011. Eligible patients had a life expectancy of 16 weeks or more and an Eastern Cooperative Oncology Group performance status of 1 or less, and could have received a maximum of one previous line of chemotherapy. Participants received induction treatment of 10 mg/kg intravenous ipilimumab every 3 weeks to a total of four doses, and 100 mg/m 2 intravenous fotemustine weekly for 3 weeks and then every 3 weeks from week 9 to week 24. Patients with a confirmed clinical response were eligible for maintenance treatment from week 24, with ipilimumab every 12 weeks and fotemustine every 3 weeks. The primary endpoint was the proportion of patients with immune-related disease control as established with immune-related response criteria. Analyses were done per protocol. This trial is registered with EudraCT, number 2010-019356-50, and with ClinicalTrials.gov, number NCT01654692. Findings: 86 patients were eligible for treatment, of whom 20 had asymptomatic brain metastases at baseline. 40 patients in the study population achieved disease control (46·5%, 95% CI 35·7-57·6), as did ten with brain metastases (50·0%, 27·2-72·8). 47 patients (55%) had grade 3 or 4 treatment-related adverse events, of which the most common was myelotoxicity (thrombocytopenia in 21 [24%] patients and neutropenia in 16 [19%]). The most common grade 3 or 4 immune-related adverse events were hepatic: 21 patients (24%) had grade 3 or 4 increases in concentrations of alanine aminotransferase or aspartate aminotransferase. Interpretation: The combination of ipilimumab plus fotemustine has clinical activity in patients with metastatic melanoma, including those with brain metastases. Funding: Bristol-Myers Squibb.
UR - http://www.scopus.com/inward/record.url?scp=84865567547&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84865567547&partnerID=8YFLogxK
U2 - 10.1016/S1470-2045(12)70324-8
DO - 10.1016/S1470-2045(12)70324-8
M3 - Article
C2 - 22894884
AN - SCOPUS:84865567547
VL - 13
SP - 879
EP - 886
JO - The Lancet Oncology
JF - The Lancet Oncology
SN - 1470-2045
IS - 9
ER -