Among patients with advanced melanoma, twice as many survived to 5 years if they received ipilimumab plus dacarbazine than if they received placebo plus dacarbazine as part of a phase III randomized clinical trial, according to a report published online Feb. 23 in the Journal of Clinical Oncology.
The investigators described their analysis as the first examination of long-term survival after a course of ipilimumab therapy, as well as the first analysis of safety outcomes in a small subset of patients who continued to receive ipilimumab as maintenance therapy. They performed this milestone survival analysis “to confirm prior reports of long-term survival in a proportion of patients from nonrandomized phase II studies,” and their findings do in fact confirm those reports, said Dr. Michele Maio of University Hospital of Siena (Italy) and her associates.
The industry-sponsored study (CA184-024) involved 502 adults with treatment-naive unresectable stage III or IV melanoma who were randomly assigned to receive ipilimumab plus dacarbazine (250 patients) or placebo plus dacarbazine (252 patients) for 10 weeks. Those who showed stable disease, a partial response, or a complete response at week 24 were permitted to continue on ipilimumab or placebo as maintenance therapy every 12 weeks thereafter.
At a minimum follow-up of 5 years, 40 patients (18.2%) in the ipilimumab group and 20 (8.8%) in the placebo group were still alive. Five-year survival with ipilimumab was not only double that with placebo, it also was roughly double the historical survival rate of patients with stage IV melanoma, which is approximately 10%, Dr. Maio and her associates reported (J. Clin. Oncol. 2015 Feb. 23 [doi:10.1200/JCO.2014.56.6018]).
With ipilimumab, 3 long-term survivors (7.5%) achieved a complete response, 17 (42.5%) had a partial response, and 11 (27.5%) achieved stable disease. In contrast, with placebo no long-term survivors achieved a complete response, 7 (35%) had a partial response, and 8 (40%) had stable disease.
There were no grade 5 adverse events. Grade 3-4 adverse events were confined to the skin and comprised pruritus and rash. Low-grade adverse events included rash, vitiligo, pruritus, GI problems, and an increased ALT or AST level.
The subset of study participants who used ipilimumab maintenance therapy was small (seven patients) but “provides some insight into the safety profile of ipilimumab during extended treatment.” The only high-grade adverse events were pruritus and rash, which affected only one patient.
“This analysis demonstrates that a proportion of treatment-naive patients with advanced melanoma can achieve durable, long-term survival with ipilimumab therapy,” Dr. Maio and her associates wrote.