Ipilimumab plus Sargramostin for Metastatic Melanoma

Chicago—After a year of treatment, 68.9% of patients with metastatic melanoma who took ipilimumab plus sargramostin were alive compared with 52.9% of patients who received ipilimumab alone, according to a multicenter, randomized, phase 2 trial. The median overall survival was 17.5 months in the combination group and 12.7 months in the monotherapy group, which was statistically significant (hazard ratio, 0.64; P=.014).

In addition, adding sargramostin to ipilimumab reduced the incidence of high-grade adverse events and serious gastrointestinal and pulmonary side effects, according to F. Stephen Hodi, MD, the study’s lead author. He presented the results in an oral abstract session at the ASCO meeting. Bristol-Myers Squibb and Sanofi, the marketers of ipilimumab and sargramostin, respectively, supported the study, as did the National Cancer Institute.

In March 2011, the FDA approved ipilimumab to treat late-stage melanoma. Patients who took the fully human monoclonal antibody alone or in combination with an experimental tumor vaccine had an improvement in overall survival compared with those who received only the vaccine. However, 10% to 25% of patients who took ipilimumab had high-grade adverse events.

Sargramostin, a recombinant human granulocyte-macrophage colony-stimulating factor, is FDA approved for several indications, including for bone marrow support following high-dose chemotherapy. Sargramostin helps increase the number and function of white blood cells.

In this study, the authors randomized 245 patients with unresectable stage 3 or 4 disease in a 1:1 ratio to receive ipilimumab administered intravenously plus sargramostin administered subcutaneously or ipilimumab alone. Patients were included if they had received ≤1 prior therapy, no evidence of central nervous system disease, and an Eastern Cooperative Oncology Group performance status score of 0 or 1.

The dosage for sargramostin was 250 mcg once daily on days 1 to 14 of a 21-day cycle. The induction dosage of ipilimumab was 10 mg/kg on day 1 of a 21-day cycle. Patients took that dosage for 4 cycles and then received 10 mg/kg on day 1 of every fourth cycle.

The current FDA-approved dosage of ipilimumab is 3 mg/kg every 3 weeks for a total of 4 doses. Dr. Hodi mentioned that recently accrual for a trial comparing 3 mg/kg and 10 mg/kg of ipilimumab had been completed, although the data had not been analyzed or released.

Patients were enrolled from December 28, 2010, to July 28, 2011. The median follow-up was 13.3 months, and the data was analyzed in March 2013.

The overall response rates were 15.5% in the ipilimumab plus sargramostin group and 14.8% in the ipilimumab alone group. The difference was not statistically significant (P=.88). Two patients, both in the combination group, had a complete response.

After 6 months of treatment, the progression-free survival rates were 29.6% in the ipilimumab group and 34.0% in the ipilimumab plus sargramostin group. The difference was not statistically significant (P=.569). The median progression-free survival in each group was 3.1 months.

Dr. Hodi noted that there were 2 chronic perforations in the ipilimumab plus sargramostin group and 7 chronic perforations in the ipilimumab alone group. He added that there was a statistically significant improvement in high-grade adverse events for patients who took the combination treatment (P=.038), including for treatment-related gastrointestinal and pulmonary adverse events (P=.047 and P=.030, respectively).