Abstract
9025 Background: Ipilimumab and tremelimumab are human monoclonal antibodies against cytotoxic T-lymphocyte antigen-4 (CTLA-4). Ipilimumab was the first agent to show a statistically significant benefit in overall survival with durable-long-term responses for advanced melanoma patients both in first-and second-line setting. Up to date, there is no proven association between the BRAF-V600E mutation and the disease control rate (DCR) in response to Ipilimumab. Moreover, significantly shorter survival rates have been reported in patients harboring an NRAS mutation than in those without. This retrospective analysis was carried out to assess if BRAF (V600) and NRAS mutation status affects the clinical outcome of Ipilimumab-treated melanoma patients. Methods: This is a retrospective multi-center analysisof 71 patients, with confirmed BRAF and NRAS mutation status, treated with anti-CTLA-4 antibodies from December 2006 until August 2012. The cut-off for the estimation of overall survival was end of November 2012. Results: The median overall survival of BRAFV600/NRAS mutant patients (n=44) was 1,41 years compared with 2.67 years in BRAF/NRAS wild-type patients (n=27). Although this difference was not statistically significant there was a trend for improved survival in wild-type patients. Of the 71 patients analyzed, 56 received chemotherapy prior to Ipilimumab. In the BRAF/NRAS mutant cohort, 12 patients received Ipilimumab following either a BRAF- or a MEK- inhibitor. Of those 12 patients, 8 progressed and were unable to complete Ipilimumab. Of the 4 patients who completed 4 cycles of Ipilimumab, 2 were subsequently treated with a BRAF inhibitor. Furthermore out of the 71 patients, 8 patients received a BRAF or a MEK inhibitor after progression; 5 of them are still alive. Conclusions: This is the first retrospective study to evaluate the association of both BRAF and NRAS mutational status with the overall survival of Ipilimumab-treated patients. There was a trend towards an improved survival in the BRAF/NRAS wild-type subpopulation. Additional patients will be examined to foster these preliminary results.
Highlights
Melanoma has been long considered an immunogenic cancer based on reports of spontaneous regression and some tumor responses after immune-stimulating agent treatment [1,2,3]
Inorder to turn on the immune system against cancer another promishing approach, focused on blocking the negative-regulator of T-cell responses, the cytotoxic T-lymphocyte-associate antigen (CTLA-4), which marked a new era in the treatment of advanced melanoma and oncoimmunotherapy [4]
Tremelimumab failed to significantly improve overall survival (OS) over standard chemotherapy [7]. This was partly explained due to patients’ selection criteria, as patients with LDH levels greater than 2x upper limit of normal (2xULN) were excluded according to the study protocol. Another explanation was the unintended crossover to ipilimumab in the control arm, as crossover to tremelimumab was not allowed within the study protocol
Summary
Melanoma has been long considered an immunogenic cancer based on reports of spontaneous regression and some tumor responses after immune-stimulating agent treatment [1,2,3] Taking this into consideration, multiple efforts in cytokine therapy, tumor vaccines, and adoptive immunotherapy have been pursued to harness the immune response to tackle melanoma but have had slow progress over the decades [1]. Tremelimumab failed to significantly improve OS over standard chemotherapy [7] This was partly explained due to patients’ selection criteria, as patients with LDH levels greater than 2x upper limit of normal (2xULN) were excluded according to the study protocol. Another explanation was the unintended crossover to ipilimumab in the control arm, as crossover to tremelimumab was not allowed within the study protocol
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
