Open-label, multicohort, phase 1b clinical trials (enrollment, December 2011-September 2013). Median duration of follow-up was 21 months. The study was performed in academic medical centers in Australia, Canada, France, and the United States. Eligible patients were aged 18 years and older and had advanced or metastatic melanoma. Data were pooled from 655 enrolled patients (135 from a nonrandomized cohort [n = 87 ipilimumab naive; n = 48 ipilimumab treated] and 520 from randomized cohorts [n = 226 ipilimumab naive; n = 294 ipilimumab treated]). Pembrolizumab 10 mg/kg every 2 weeks, 10 mg/kg every 3 weeks, or 2 mg/kg every 3 weeks continued until disease progression, intolerable toxicity, or investigator decision.
Among the 655 patients (median [range] age, 61 [18-94] years; 405 [62%] men), 581 had measurable disease at baseline. An objective response was reported in 194 of 581 patients (33%) and in 60 of 133 treatment-naive patients (45%). Overall, 74% (152/205) of responses were ongoing at the time of data cutoff; 44% (90/205) of patients had response duration for at least 1 year and 79% (162/205) had response duration for at least 6 months. Twelve-month progression-free survival rates were 35% in the total population and 52% among treatment-naive patients. Median overall survival in the total population was 23 months, with a 12-month survival rate of 66%, and a 24-month survival rate of 49%. In treatment-naive patients, median overall survival was 31 months, with a 12-month survival rate of 73%, and a 24-month survival rate of 60%. Ninety-two of 655 patients (14%) experienced at least 1 treatment-related grade 3 or 4 adverse event (AE) and 27 of 655 (4%) patients discontinued treatment because of a treatment-related AE. Treatment-related serious AEs were reported in 59 patients (9%). There were no drug-related deaths.
Among patients with advanced melanoma, pembrolizumab administration was associated with an overall objective response rate of 33%, 12-month progression-free survival rate of 35%, and median overall survival of 23 months; grade 3 or 4 treatment-related AEs occurred in 14%.
Once again it is clear that treatment naive patients do better on anti-PD1 than those who are pretreated...particularly with ipi. Here is a post and link to the report from the Checkmate 064 trial in which folks who got nivo first followed by ipi had slightly more side effects (roughly 50 vs 43%) but they also had objective response rates of 41.2% vs only 20% in the ipi first group!!!!!!!!!!!!!!!! - Sequential nivo then ipi vs Sequential ipi then nivo
Here is a recent report on OS with nivo - Nivolumab shows impressive OS in melanoma
The data here is further out. All patients were "heavily pre-treated", so none were treatment naive, but none had been treated with ipi.
We never can compare apples to apples, can we? But...still....good news overall! Way to go, Ratties! - c