125 days, = 0.09) although this was not statistically significant (Fig. excellent outcomes to pembrolizumab compared to rapid progressors (PFS 45 days; ORR 55% vs. 25%, CBR 80% vs. 25%, median PFS 249 vs. 50 days). Using logistic regression models, PFS to ipilimumab was independently correlated Nafamostat mesylate with response to pembrolizumab Nafamostat mesylate (OR 1.22, 95% CI 1.02C1.51). This study shows that prolonged PFS to ipilimumab predicts excellent outcomes to subsequent pembrolizumab, offering valuable prognostic information for clinicians. = 76) and Vanderbilt University (= 40) were collected. All patients who received at least one dose of both ipilimumab and pembrolizumab were included in the analysis. At the time of analysis, all surviving patients had been followed for a minimum of 80 days after treatment with pembrolizumab. For this study, we included only patients who received therapy sequentially; we did Nafamostat mesylate not include patients treated with combined ipilimumab and nivolumab. Study Design Demographic data including age, sex, site of metastatic disease, and lactate dehydrogenase were recorded. We collected treatment results, including objective response (by RECIST 1.1 criteria), progression-free survival, and overall survival for each Nafamostat mesylate therapy (11). Interval therapy between ipilimumab and pembrolizumab was also recorded. Tumor response was assessed by cross-sectional imaging after four cycles of ipilimumab, unless clinically deterioration necessitated imaging before all cycles were completed. Ipilimumab was administered at the FDA approved dose of 3 mg/kg. Pembrolizumab was administered at 2 mg/kg every 3 weeks as standard therapy or part of an expanded access program, or at various doses (2C10 mg/kg every 2C3 weeks) through clinical trials. Statistics Progression free survival (PFS) was calculated as the time from the first dose of therapy to the date of documented disease progression, and was assessed for ipilimumab and pembrolizumab, respectively. Overall survival (OS) was calculated as the time from therapy start to time of death for any reason. Patients were censored at their last follow-up. Per RECIST 1.1 criteria, complete response was defined as the resolution of all lesions and the absence of new lesions and partial response as a decrease in tumor burden by 30% from the baseline measurements. Objective response rate (ORR) was defined as the rate of complete or partial responses (CR or PR); clinical benefit rate (CBR) was defined as the aggregate of complete and partial responses, and stable disease (SD) lasting at least 3 months (CR + PR + SD). The outcomes to pembrolizumab were assessed in relation to PFS on prior ipilimumab. We assessed PFS to ipilimumab as a continuous variable and correlated with response to pembrolizumab using ordinal logistic regression models, controlled for age, prior therapies, treatment center, metastatic stage, and lactate dehydrogenase (LDH). Ordinal regression models considered progressive disease, Rabbit Polyclonal to OR6Q1 stable disease, and objective response (CR/PR) as ordinal outcomes. We also performed Cox proportional hazards analysis controlling for the same variables to determine whether PFS to ipilimumab predicted PFS to subsequent pembrolizumab. We stratified patients with 90 day PFS and 90 day PFS and compared their response to subsequent anti-PD-1 using chi-square testing, and compared subsequent PFS and OS to anti-PD-1 between these two groups using the log rank test. We performed similar analyses stratifying by more extreme values of ipilimumab PFS: 45 days (rapid progression) compared to ipilimumab PFS of 180 days (prolonged benefit). For proof of concept, we also performed these analyses using cutoffs of 60/120 days and stratifying into tertiles. = 42) and 63% of patients were male (= 73) (Table 1). Ages ranged from 24 to 88 with a mean of 63 years. Some patients (59%, = 69) received no treatment prior to ipilimumab. Table 1 Patient Demographics = 86) had progressive disease as their best response to ipilimumab, 6% (= 7) had a partial response and 18% (= 21) had stable disease. Following treatment with ipilimumab, 67 patients had an interim treatment, whereas the remaining patients were Nafamostat mesylate treated with pembrolizumab immediately after progression on ipilimumab. Of all patients then treated with pembrolizumab, 35% (= 41) had a partial response, 7% (= 8) had a complete response, 14% (= 16) had stable disease, and 44% (= 51) had primary disease progression on pembrolizumab, with a median PFS of 176 days. The median OS from the time of ipilimumab administration was not reached; at the time of analysis 67% of patients remained alive (= 77). The median time between ipilimumab and pembrolizumab initiation was 257 days, and the.
125 days, = 0