MedicalResearch.com Interview with:
Dr Paolo A Ascierto MD
Melanoma Cancer Immunotherapy and Innovative Therapy Unit
Istituto Nazionale Tumori Fondazione
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Although IPI was approved for the treatment of melanoma at dosage of 3 mg/kg, a dose-ranging phase 2 trial suggested longer overall survival (OS) but more treatment-related adverse events with ipilimumab 10 mg/kg vs 3 mg/kg. However, the study MDX010-020 (randomized phase III study which compared ipilimumab 3 mg/kg + gp100 vaccination and ipilimumab 3mg/kg + placebo vs gp100 vaccination + placebo) performed as second line treatment of advanced melanoma patients, showed an OS curve similar to that of the study CA184-169 (randomized phase III study which compared dacarbazine + ipilimumab 10 mg/kg to dacarbazine + placebo) as first line treatment of metastatic melanoma.
For this reason FDA approved ipilimumab at dosage of 3 mg/kg as first and second line treatment for advanced melanoma, but asked for a randomized phase III study of comparison of ipilimumab at the different dosage in order to explore if there was a difference in the outcome of patients with different dosages.
MedicalResearch.com: What should readers take away from your report?
Response: The results showed that the dosage can make the difference in reaching a long term benefit. The ipilimumab at dosage of 10 mg/kg showed a better survival rate at 1-, 2-, and 3- years of that reached with the lower dosage: 54,3%, 38,5%, and 31,2% in the 10 mg/kg group and 47,6%, 31,0%, and 23,2% in the 3 mg/kg group respectively.
No differences were observed in terms of responses or PFS, while ipilimumab 10 mg/kg confirmed to be associated with higher rates of treatment-related adverse events.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: The combination of ipilimumab/nivolumab or anti-PD-1s treatment alone (nivolumab, pembrolizumab) showed to be superior to the treatment with ipilimumab monotherapy. The results from the 169 study won’t affect the first line treatment of advanced melanoma. However, ipilimumab 10 mg/kg could have a role in patients refractory to previous immunotherapy. This should be explored in future studies.
Another comment regarding the dosage of ipilimumab in the combination with nivolumab. In melanoma, it seems that ipilimumab 3 mg/kg is the best dosage. However, considering the higher rate of adverse events, there are some trials ongoing which are exploring a schedule with lower dosage of ipilimumab. After the result of 169 study where it was clear that higher dosage of ipilimumab is better, the strategy to reduce ipilimumab dosage in the combination could reduce side effect but also efficacy.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Ipilimumab 10 mg/kg versus ipilimumab 3 mg/kg in patients with unresectable or metastatic melanoma: a randomised, double-blind, multicentre, phase 3 trial
Ascierto, Paolo A et al.
The Lancet Oncology , Volume 0 , Issue 0 , 27 March 2017
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