Assessment of association between BRAF-V600E mutation status in melanomas and
clinical response to ipilimumab.
Author(s): Shahabi V, Whitney G, Hamid O, Schmidt H, Chasalow SD, Alaparthy S, Jackson JR.
Affiliation(s): Bristol-Myers Squibb Company, Princeton, NJ, USA. vafa.shahabi@bms.com
Publication date & source: 2012, Cancer Immunol Immunother. , 61(5):733-7
Ipilimumab, a fully human monoclonal antibody against cytotoxic T lymphocyte
antigen-4, has demonstrated significant improvement in overall survival in
previously treated advanced melanoma patients. The BRAF inhibitor, vemurafenib,
has shown up to 78% objective response rates in melanoma patients harboring the
BRAF-V600E mutation but not in patients lacking the mutation. As an immune
potentiator, the mechanism of action of ipilimumab may not be dependent of the
activity of the BRAF pathway. To test this, we investigated whether the clinical
activity of ipilimumab would be affected by the BRAF-V600E mutation status of the
tumors. Thus, this retrospective analysis was carried using a set of tumor
biopsies from a completed phase II clinical trial. CA184004 was a randomized,
double-blind, multicenter trial of 82 previously treated or untreated patients
with unresectable stage III/IV melanoma. Patients received ipilimumab 3 or
10 mg/kg every 3 weeks for four doses followed by maintenance dosing in eligible
patients. The BRAF-V600E mutation status for 80 patients was determined in tumor
biopsies by PCR-based assays. Data on disease control were available for 69
patients with evaluated BRAF-V600E mutation status. Rates of objective responses
and stable disease in patients with BRAF-V600E mutation positive tumors (30%)
were comparable to those in patients with the wild-type gene (~33%). Eleven
patients displayed Durable Disease Control (DDC) of which 55% had BRAF-V600E
mutation positive tumors and 45% did not. In the 48 patients showing no DDC, the
mutation frequency was 50%. In this study, no association between BRAF-V600E
mutation status of melanoma tumors and DDC after treatment with ipilimumab was
detected.
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