Pembrolizumab effective, well-tolerated in advanced melanoma patients

Apr 30 2015

By Shreeya Nanda, Senior medwireNews Reporter

Compared with ipilimumab, treatment with pembrolizumab not only significantly improves outcomes, but also results in fewer high-grade adverse events in patients with advanced melanoma, a phase III trial shows.

Indeed, the interim overall survival (OS) results favouring pembrolizumab resulted in early trial closure to allow ipilimumab-treated patients the option of receiving the programmed cell death (PD)-1 inhibitor instead, say Caroline Robert (Gustave Roussy and Paris-Sud University, France) and colleagues.

The phase III KEYNOTE-006 trial comparing PD-1 inhibition with the cytotoxic T-lymphocyte–

associated protein-4 blockade agent ipilimumab included 834 patients with unresectable stage III or IV disease who had received no more than one systemic treatment.

The estimated 6-month progression-free survival rate was 47.3% for the 279 patients randomly assigned to receive pembrolizumab 10 mg/kg every 2 weeks, 46.4% for the 277 patients given pembrolizumab 10 mg/kg every 3 weeks and 26.5% for the 278 patients treated with four doses of ipilimumab 3 mg/kg every 3 weeks.

Pembrolizumab, irrespective of dosing frequency, reduced the risk of disease progression by 42% compared with ipilimumab.

Treatment with pembrolizumab also significantly extended OS, with estimated 1-year OS rates of 74.1% and 68.4% for patients receiving pembrolizumab every 2 weeks and every 3 weeks, respectively, versus 58.2% for ipilimumab-treated patients, with the 2-week and 3-week regimens reducing the risk of death by 37% and 31%, respectively.

And patients given pembrolizumab also had a significantly higher response rate than those treated with ipilimumab, at, respectively, 33.7% and 32.9% for the 2- and 3- week regimens versus 11.9%. Moreover, at the time of analysis, responses were ongoing in 89.4%, 96.7% and 87.9% of patients in the pembrolizumab every 2 weeks, pembrolizumab every 3 weeks and ipilimumab groups, respectively.

“There were no apparent differences in efficacy between the two pembrolizumab regimens tested in this study, neither of which is the dose that is approved in the United States (2 mg per kilogram every 3 weeks)”, notes the team in The New England Journal of Medicine.

Treatment-related adverse events of grade 3 or higher occurred in 13.3%, 10.1% and 19.9% of patients receiving the 2- and 3-week regimens of pembrolizumab and ipilimumab, respectively.

Colitis was the most frequently observed adverse event of special interest of grade 3 or higher in the pembrolizumab-treated patients, at 1.4% and 2.5% in the 2-week and 3-week treatment arms, respectively. This was also the case in the ipilimumab group, with an incidence of 7.0%.

Robert et al point out that pembrolizumab treatment resulted in less high-grade toxicity than ipilimumab despite a three-times longer duration of exposure.

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