Dermopathic Institute of the Immaculate IDI IRCCS

Rome, Italy

Dermopathic Institute of the Immaculate IDI IRCCS

Rome, Italy

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Ascierto P.A.,Instituto Nazionale Tumori Fondazione G Pascale | Simeone E.,Instituto Nazionale Tumori Fondazione G Pascale | Sileni V.C.,Veneto Institute of Oncology IOV IRCCS | Pigozzo J.,Veneto Institute of Oncology IOV IRCCS | And 17 more authors.
Journal of Translational Medicine | Year: 2014

Background: Ipilimumab 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).Methods: Ipilimumab 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.Results: Of 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.Conclusions: Outside 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. © 2014 Ascierto et al.; licensee BioMed Central Ltd.


Ascierto P.A.,Instituto Nazionale Tumori Fondazione G Pascale | Simeone E.,Instituto Nazionale Tumori Fondazione G Pascale | Sileni V.C.,Veneto Institute of Oncology IOV IRCCS | Vecchio M.D.,Italian National Cancer Institute | And 17 more authors.
Cancer Investigation | Year: 2014

Of 93 patients with pretreated, BRAFV600 mutation-positive advanced melanoma who received vemurafenib or dabrafenib before (n = 45) or after (n = 48) treatment with ipilimumab 3 mg/kg, median overall survival (mOS) from first treatment was 9.9 and 14.5 months, respectively. Among patients treated with a BRAF inhibitor first, mOS from the end of BRAF inhibition was 1.2 months for those who did not complete ipilimumab treatment as per protocol, compared with 12.7 months for those who did (p < .001). Prospective, randomized studies are required to determine the optimal sequencing of ipilimumab and BRAF inhibitors in patients with BRAF-mutated metastatic melanoma. Copyright © 2014 Informa Healthcare USA, Inc.


Sileni V.C.,Oncology Institute of Veneto IRCCS | Pigozzo J.,Oncology Institute of Veneto IRCCS | Ascierto P.A.,Instituto Nazionale Tumori Fondazione G Pascale | Grimaldi A.M.,Instituto Nazionale Tumori Fondazione G Pascale | And 18 more authors.
Journal of Experimental and Clinical Cancer Research | Year: 2014

Background: Elderly patients with metastatic melanoma have different disease characteristics and a poorer prognosis than younger patients. Data from clinical trials and expanded access programmes (EAPs) suggest ipilimumab confers a consistent survival benefit and has a similar safety profile across different age groups of patients with metastatic melanoma. Here we report the efficacy and safety of ipilimumab 3 mg/kg in elderly patients enrolled in an EAP in Italy. Methods. Patients aged > 70 years with pretreated melanoma received ipilimumab 3 mg/kg every 3 weeks for four doses through an EAP. Tumour response was evaluated at baseline and after completion of induction therapy using immune-related response criteria and patients were monitored throughout the treatment period for adverse events (AEs), including immune-related AEs. Results: The immune-related disease control rate among 188 evaluable patients was 38%, including four patients with an immune-related complete response, 24 with an immune-related partial response and 44 with immune-related stable disease. Median progression-free survival (PFS) was 4.0 months and the 1-and 2-year PFS rates were 21% and 12%, respectively. Median overall survival (OS) was 8.9 months; 1-and 2-year OS rates were 38% and 22%, respectively. The safety profile of ipilimumab was consistent with that observed in the general population of the Italian EAP and treatment-related AEs generally resolved within a median of 2 weeks with treatment as per protocol-specific guidelines. Conclusions: These results suggest ipilimumab is a feasible treatment option in elderly patients with metastatic melanoma. Ipilimumab treatment was generally well tolerated and resulted in clinical benefit and extended survival in elderly patients treated at centres in Italy. © 2014 Chiarion Sileni et al.; licensee BioMed Central Ltd.


Chiarion-Sileni V.,Veneto Institute of Oncology IOV IRCCS | Pigozzo J.,Veneto Institute of Oncology IOV IRCCS | Ascierto P.A.,Instituto Nazionale Tumori Fondazione G Pascale | Simeone E.,Instituto Nazionale Tumori Fondazione G Pascale | And 14 more authors.
British Journal of Cancer | Year: 2014

Background:Retreatment with ipilimumab has been shown to re-establish disease control in some patients with disease progression. Here, we report the efficacy and safety of retreatment with ipilimumab 3 mg kg-1 among patients participating in an expanded access programme in Italy.Methods:Patients who achieved disease control during induction therapy were retreated with ipilimumab upon progression (3 mg kg-1 every 3 weeks for up to four doses), providing they had not experienced toxicity that precluded further dosing. Tumour assessments were conducted after retreatment, and patients were monitored throughout for adverse events.Results:Of 855 patients treated with ipilimumab, 51 were retreated upon disease progression. Of these, 28 (55%) regained disease control upon retreatment and 42% were alive 2 years after the first induction dose of ipilimumab; median overall survival was 21 months. Eleven patients (22%) had a treatment-related adverse event of any grade during retreatment. These were generally mild-to-moderate and resolved within a median of 4 days. No new types of toxicity were reported.Conclusions:For patients who meet predefined criteria, retreatment with ipilimumab is generally well tolerated and can translate into clinical benefit. This strategy should be compared with other therapeutic options in randomised controlled trials. © 2014 Cancer Research UK.


Queirolo P.,IST Instituto Nazionale Per la Ricerca Sul Cancro | Spagnolo F.,IST Instituto Nazionale Per la Ricerca Sul Cancro | Ascierto P.A.,Italian National Cancer Institute | Simeone E.,Italian National Cancer Institute | And 15 more authors.
Journal of Neuro-Oncology | Year: 2014

Patients with melanoma brain metastases have a poor prognosis and historically have been excluded from clinical trials. The Expanded Access Program (EAP) provided an opportunity to evaluate the feasibility of ipilimumab (3 mg/kg every 3 weeks for four doses) in patients with stage 3 (unresectable) or 4 melanoma and asymptomatic brain metastases, who had failed or did not tolerate previous treatments and had no other therapeutic option available. Tumor assessments were conducted at baseline and week 12 using immune-related response criteria and patients were monitored for adverse events (AEs). Of 855 patients participating in the EAP in Italy, 146 had asymptomatic brain metastases. With a median follow-up of 4 months, the global disease control rate was 27 %, including 4 patients with a complete response and 13 with a partial response. Median progression-free survival and overall survival were 2.8 and 4.3 months, respectively and approximately one-fifth of patients were alive 1 year after starting ipilimumab. In total, 29 % of patients reported a treatment-related AE of any grade, which were grade 3/4 in 6 % of patients. AEs were generally reversible with treatment as per protocol-specific guidelines. Ipilimumab shows durable benefits in some patients with advanced melanoma metastatic to the brain, with safety results consistent with those previously reported in clinical trials. © 2014 Springer Science+Business Media.


Del Vecchio M.,Fondazione IRCCS Instituto Nazionale Dei Tumori | Di Guardo L.,Fondazione IRCCS Instituto Nazionale Dei Tumori | Ascierto P.A.,Instituto Nazionale Tumori Fondazione G Pascale | Grimaldi A.M.,Instituto Nazionale Tumori Fondazione G Pascale | And 15 more authors.
European Journal of Cancer | Year: 2014

Background Mucosal melanoma is an extremely rare and aggressive malignancy that often remains undetected until it reaches an advanced stage, when effective treatment options are limited. The activity and safety of ipilimumab were assessed in an Expanded Access Programme (EAP) that included patients with metastatic, mucosal melanoma. Methods Ipilimumab was available upon physician request for patients aged ≥16 years with stage III (unresectable) or IV skin, ocular or mucosal melanoma, who had failed or did not tolerate previous treatments and had no other therapeutic option 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 using immune-related response criteria. Patients were monitored for adverse events (AEs), including immune-related AEs, within 3 to 4 days of each scheduled visit. Results Of 855 patients participating in the EAP in Italy, 71 (8%) had metastatic, mucosal melanoma. With a median follow-up of 21.8 months, the response rate was 12% and the immune-related disease control rate was 36%. Median progression-free survival and overall survival were 4.3 and 6.4 months, respectively. In total, 34% of patients reported treatment-related AEs of any grade, which were grade 3 or 4 in 9% of patients. AEs were generally manageable as per protocol-specific guidelines. Conclusion/interpretation Ipilimumab may be a feasible treatment option in pretreated patients with metastatic mucosal melanoma, and warrants further investigation in prospective clinical trials. © 2013 Elsevier Ltd. All rights reserved.


Picardi A.,Italian National Institute of Health | Bartone P.T.,National Defense University | Querci R.,ASL Citta di Milan | Bitetti D.,Dermopathic Institute of the Immaculate IDI IRCCS | And 9 more authors.
Rivista di Psichiatria | Year: 2012

Studies have shown that psychological hardiness is an important stress resilience resource for individuals. The 15-item Dispositional Resilience Scale (DRS-15) is a short, reliable and valid self-report instrument to measure hardiness that is not available in Italian. The present study was undertaken to create an Italian version of the DRS-15, and evaluate its psychometric properties and validity in the Italian context. An Italian version was produced using multiple independent bilingual translators. This version was administered to a non-clinical sample of adults (N=150), along with measures of psychological well-being (PWB-18) and health. A sub-sample (N=66) completed the DRS-15 again one month later. Results showed good reliability in terms of internal consistency and test-retest stability. With regard to the subscales, stability was high for all three subscales, whereas two subscales (Commitment and Control) showed marginal internal consistency. DRS-15 total and subscale scores showed a theoretically meaningful pattern of correlations with PWB-18 subscales, supporting the validity of the Italian DRS. Also, multiple regression analysis revealed a correlation between DRS-15 scores and self-rated general health, even after controlling for age and sex. The new Italian DRS-15 provides a valid, reliable and easy to use tool for assessing stress resilience in clinical and research settings.


Simeone E.,Instituto Nazionale Tumori Fondazione G Pascale | Gentilcore G.,Instituto Nazionale Tumori Fondazione G Pascale | Giannarelli D.,Regina Elena Cancer Institute | Grimaldi A.M.,Instituto Nazionale Tumori Fondazione G Pascale | And 20 more authors.
Cancer Immunology, Immunotherapy | Year: 2014

Background: Ipilimumab can induce durable disease control and long-term survival in patients with metastatic melanoma. Identification of a biomarker that correlates with clinical benefit and potentially provides an early marker of response is an active area of research. Patients and methods: Ipilimumab was available upon physician request for patients aged ≥16 years with stage III (unresectable) or IV cutaneous, ocular or mucosal melanoma, who had failed or did not tolerate previous treatments and had no other therapeutic option available. Patients received ipilimumab 3 mg/kg every 3 weeks for four doses. Tumour assessments were conducted at baseline, Week 12 and Week 24 using immune-related response criteria. Patients were monitored continuously for adverse events (AEs), including immune-related AEs. Candidate immunological markers were evaluated in peripheral blood and sera samples collected at baseline and Weeks 4, 7, 10 and 12. Results: Among 95 patients treated with ipilimumab 3 mg/kg, the immune-related disease control rate at Week 24 was 38 %. With a median follow-up of 24 months, median overall survival was 9.6 months. Both disease control and survival were significantly associated with decreasing levels of lactate dehydrogenase, C-reactive protein and FoxP3/regulatory T cells, and increasing absolute lymphocyte count, between baseline and the end of dosing (Week 12). Conclusion: Ipilimumab is a feasible treatment option for heavily pretreated patients with metastatic melanoma. Changes in some immunological markers between baseline and the fourth ipilimumab infusion appear to be associated with disease control and survival, but verification in prospective clinical trials is required. © 2014 Springer-Verlag.


Maio M.,University of Siena | Danielli R.,University of Siena | Chiarion-Sileni V.,Veneto Oncology Institute IRCCS | Pigozzo J.,Veneto Oncology Institute IRCCS | And 14 more authors.
Annals of Oncology | Year: 2013

Background: Patients with advanced uveal melanoma have a poor prognosis and limited treatment options. Ipilimumab is approved for pre-treated adult patients with advanced melanoma. However, because previous clinical trials with ipilimumab have excluded patients with uveal melanoma, data in this patient population are limited. Patients and methods: Pre-treated patients with advanced uveal melanoma received ipilimumab 3 mg/kg through an expanded access programme, every 3 weeks for four doses. Tumour assessments were conducted at baseline and after completion of treatment and patients were monitored throughout for adverse events. Results: Among 82 assessable patients, 4 (5%) had an immune-related objective response and 24 (29%) had immunerelated stable disease lasting ≥3 months for an immune-related disease control rate of 34%. With a median follow-up of 5.6 months, median overall survival (OS) was 6.0 months and median progression-free survival (PFS) was 3.6 months. The 1-year rates of OS and PFS were 31% and 11%, respectively. The safety profile of ipilimumab was similar to that in patients with cutaneous melanoma. Conclusions: These data suggest ipilimumab 3 mg/kg is a feasible option in pre-treated patients with metastatic uveal melanoma. Evidence of disease control and a 1-year survival rate of 31% indicate the need for further investigation in randomised, controlled trials to determine the optimal timing and use of ipilimumab in this patient population. © The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology All rights reserved.


PubMed | Instituto Nazionale Tumori Fondazione G Pascale, Regina Elena Cancer Institute, Italian National Cancer Institute, University of Rome La Sapienza and 7 more.
Type: Journal Article | Journal: European journal of cancer (Oxford, England : 1990) | Year: 2013

Mucosal melanoma is an extremely rare and aggressive malignancy that often remains undetected until it reaches an advanced stage, when effective treatment options are limited. The activity and safety of ipilimumab were assessed in an Expanded Access Programme (EAP) that included patients with metastatic, mucosal melanoma.Ipilimumab was available upon physician request for patients aged 16years with stage III (unresectable) or IV skin, ocular or mucosal melanoma, who had failed or did not tolerate previous treatments and had no other therapeutic option available. Patients received ipilimumab 3mg/kg every 3weeks 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 using immune-related response criteria. Patients were monitored for adverse events (AEs), including immune-related AEs, within 3 to 4days of each scheduled visit.Of 855 patients participating in the EAP in Italy, 71 (8%) had metastatic, mucosal melanoma. With a median follow-up of 21.8months, the response rate was 12% and the immune-related disease control rate was 36%. Median progression-free survival and overall survival were 4.3 and 6.4months, respectively. In total, 34% of patients reported treatment-related AEs of any grade, which were grade 3 or 4 in 9% of patients. AEs were generally manageable as per protocol-specific guidelines.Ipilimumab may be a feasible treatment option in pretreated patients with metastatic mucosal melanoma, and warrants further investigation in prospective clinical trials.

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