The investigational agent ipilimumab is showing promise as a therapy for both treatment-naïve and previously treated patients with late-stage melanoma, according to phase 2 results released here at the 33rd Congress of the European Society for Medical Oncology (ESMO).
Ipilimumab is a fully human, anticytotoxic T-lymphocyte antigen-4 (CTLA-4) monoclonal antibody that has shown durable responses in previously treated patients with advanced melanoma.
Ruggero Ridolfi, MD, with the Istituto Scientifico Romagnolo per lo Studio e la Cura del Tumori (IRST) in Meldova, Italy, presented results in 115 patients who received ipilimumab, 10 mg, kg every three weeks for four weeks. Subjects were then eligible to receive maintenance dosing every 12 weeks starting at week 24.
After the initial four weeks of ipilimumab therapy, patients were randomized to prophylactic budesonide or placebo.
All participants in the trial had unresectable stage III or IV melanoma and were treatment- naïve or had been previously treated with systemic anticancer therapy.
The primary endpoint was the rate of grade 2 or greater diarrhea before week 24.
Grade 2 or greater diarrhea rates were similar in treatment-naïve and previously treated groups. Thus, the rate of grade 2 or greater diarrhea in treatment-naïve patients assigned to ipilimumab plus placebo was 31.3% and 38.1% for the group who got ipilimumab plus budesonide. Previously treated patients had Grade 2 or greater diarrhea rates of 40.0% and 29.7% in the two groups, respectively.
The best overall response rate (BORR), a secondary endpoint, did not differ appreciably in patients who did or did not receive prior therapy. That is, treatment- naïve patients assigned to ipilimumab plus placebo had a 15.6% BORR versus 9.5% in treatment-naïve patients who received ipilimumab plus budesonide.
The BORR in previously treated patients was 16.0% and 13.5% for the two treatment groups, respectively.
The median overall survival rate has not yet been reached in treatment-naïve patients but was 14.8 months in ipilimumab plus placebo cohort and 8.5 months in the ipilimumab plus budesonide cohort.
Elsewhere at the meeting, investigators reported that 10 mg/kg is the optimal ipilimumab dose. The results are drawn from a phase 2 study that examined doses of 10 mg/kg, 3 mg/kg, and 0.3 mg/kg in patients with unresectable stage III or IV melanoma who had relapsed, failed to demonstrate a response after at least 12 weeks’ treatment with an earlier treatment regimen, or were unable to tolerate prior therapies.
In another phase 2 study, ipilimumab, at a dose of 10 mg/kg, showed clinical activity in patients with advanced melanoma who had progressed on prior therapies.
Written by Jill Stein
Jill Stein is a Paris-based freelance medical writer.
jillstein03(at)gmail.com