University of Washington/Seattle Cancer Care Alliance Experience with Single Agent Ipilimumab in Advanced Unresectable/Metastatic Melanoma

Abstract

Background: Ipilimumab immunotherapy was the first treatment ever to be associatedwith improved survival in a phase III clinical trial of patients with metastatic melanoma and was approved by the US Food and Drug Administration (FDA) in 2011. However, the response rates with ipilimumab are low (~10%) and toxicities considerable. The optimal dose and schedule still remain unclear and there is an unmet need to identify predictors of clinical benefit. To gain further insight into some of these questions, we performed this retrospective study of metastatic melanoma patients treated at the Seattle Cancer Care Alliance (SCCA). Methods:We performed a chart review on 126 patients with metastatic melanoma treatedwith single agent ipilmumab from 2006 to 2012 at the SCCA. These patients hadreceived ipilimumab at either the investigational 10 mg/kg dose (with maintenance scheduling) or the 3 mg/kg dose (without maintenance, similar to the FDA approveddose). Efficacy and safety outcomes and baseline characteristics were subjected to univariate analysis. Efficacy endpoints included overall survival (OS), progression free survival (PFS), objective response rate (ORR) and Duration of Clinical Benefit (DCB)defined as the time from Ipilimumab initiation until documented progression or change in therapy (for non-trial patients). Immune-related adverse events (IRAEs), absolute 4 lymphocyte count (ALC), concordance of disease response by metastatic site, and use of radiation therapy (RT) were also analyzed. Results:The median age was 57.7 yrs. The 3 mg/kg (N=83; 65.8%) and 10 mg/kg (N=42; 33%) cohorts matched well for standard prognostic criteria. The efficacy endpoints, including OS, PFS, DCB, and ORR (see table 2) were not significantly different for the 3 mg/kg and 10 mg/kg cohorts. However, grade III/IV IRAEs were more frequent in the 10 mg/kg group (33% vs 17%, p=0.04). There was a significant correlation between efficacy outcomes anddevelopment of IRAEs (see figure 2). Baseline ALC or changes in ALC at 7 weeks post-therapy and concurrent RT administration did not significantly correlate with improved outcomes. Conclusions: Our data supports the currently FDA approveddose of 3mg/kg. The development of IRAEs was significantly associated with clinical benefit and further confirmation of this association is warranted.