Effect of mutational status on response, PFS, or OS after treatment with IL-2 for metastatic melanoma.

Abstract

8597 Background: High dose IL-2 (HD-IL2) is the only FDA-approved treatment that induces durable complete responses (CR) and survival in patients (pts) with metastatic melanoma (MM), but it does so in only 5-10% of pts. Approximately 80% of melanomas have a mutation in either BRAF or NRAS. It is unknown if these mutations influence clinical responses to HD-IL2. We reviewed the clinical outcomes, pt and tumor characteristics, and mutational status of MM pts treated with HD-IL2. Methods: All pts (n = 209) were treated at the University of Texas MD Anderson Cancer Center (MDACC) or Beth Israel Deaconess Medical Center (BIDMC) from 2004-2009. IL-2 600,000-720,000 U/kg IV was administered every 8 hours for up to 14 doses in 5 days every 3 weeks. Tumor response was assessed by RECIST criteria after 2 cycles unless obvious progression occurred after 1 cycle. For pts with available tumor tissue (n = 64), DNA was isolated and tested for activating BRAF and NRAS mutations by mass-spectroscopy based genotyping. Mutation status was compared to best clinical response, progression free survival (PFS), and overall survival (OS). Results: Mutation results for 64 pts are available: 70% BRAF (45), 11% NRAS (7), and 19% Wild-Type (12) for both (WT/WT). Pts who achieved a CR, partial response (PR), or stable disease (SD) survived longer than pts with PD (median OS not met vs 339 days, p<0.01). There was no correlation between response, PFS, or OS and mutational status of the tumor. Women were more likely to harbor a BRAF mutation than men (91% vs 59%, p<0.01), and the mean age of pts with BRAF mutations tended to be younger (45 vs 52 years, p = 0.05). There was no correlation between the mutational status and ulceration, breslow thickness, or mitotic index of the primary tumor. Conclusions: Mutational status of tumors does not appear to impact response rate, PFS, OS to HD-IL2 for the treatment of MM. BRAF mutations are more likely to occur in females and younger patients. Genotyping of additional specimens is ongoing and will be included in the final analysis of the data. All (n = 64) BRAF (n = 45) NRAS (n = 7) WT/WT (n = 12) OS (median, years) 1.94 1.84 5.34 3.09 PFS (median, days) 57 57 171 48 % Response (CR/PR/SD) 30% 31% 29% 25% No significant financial relationships to disclose.