Nearly twice as many patients with metastatic melanoma who received a combination of ipilimumab and dacarbazine were alive after four years, suggesting that ipilimumab has long-term survival benefits.
Nearly twice as many patients with metastatic melanoma who received a combination of ipilimumab (Yervoy) and dacarbazine were alive after four years compared with patients who received dacarbazine alone, suggesting that ipilimumab has long-term survival benefits and that the combination could serve as an effective treatment regimen.
The results of the long-term follow-up were presented at the European Society for Medical Oncology (ESMO) 2012 Congress in Vienna, Austria.
Ipilimumab, which is administered intravenously, is a monoclonal antibody that blocks the cytotoxic T-lymphocyte antigen (CTLA-4) molecule. CTLA-4 is implicated in suppressing antitumor immune responses. Dacarbazine is a triazene derivative with antineoplastic activity. Both drugs are approved to treat metastatic melanoma.
The follow-up was part of the CA184-024 trial, a phase III double-blind study in which patients with metastatic melanoma who were treatment-naïve were randomized to receive either ipilimumab 10 mg/kg plus dacarbazine 850 mg/m2 (n=250) or a placebo plus dacarbazine 850 mg/m2 (n=252) given at weeks 1, 4, 7, and 10, followed by dacarbazine alone every 3 weeks through week 22. Patients who achieved stable disease or better received either ipilimumab or a placebo every 12 weeks as maintenance therapy.1
Patients in the ipilimumab arm of the study had an overall survival rate of 19.0% after 4 years (95% confidence interval [CI], 14.2—24.2) compared with 9.6% among patients in the control arm (95% CI, 6.1–13.5). The median overall survival in the ipilimumab arm was 11.2 months (95% CI, 9.4–13.6) compared with 9.1 months in the control arm (95% CI, 7.8–10.5). The study includes survival data collected through April 2012.
In a statement, manufacturer Bristol-Myers Squibb noted that the dosage of ipilimumab in this study differs from the approved 3 mg/kg dosage approved by the FDA. However, the company stated that a phase III clinical trial comparing the two dose levels is being conducted. Additionally, the combination of ipilimumab and dacarbazine is not yet a FDA-approved regimen.
In another study presented at the ESMO Congress, five-year overall survival rates for three different completed phase II trials of ipilimumab were reported. The three studies included in the analysis were CA184-008, a single-arm study of the 10 mg/kg dose of ipilimumab in previously treated patients; CA184-022, a dose-ranging study of ipilimumab at 0.3, 3, or 10 mg/kg in previously treated patients; and CA184-007, a study of ipilimumab at 10 mg/kg with or without prophylactic budesonide in treatment-naïve and previously treated patients.2
The five-year overall survival rates among all three studies were 12% to 28% in previously treated patients and 38% to 50% in treatment-naïve patients. Across the studies, the researchers found that five-year overall survival rates were similar to those observed at four years, suggesting that certain populations who receive certain dosages of ipilimumab are likely to achieve a significant survival benefit with ipilimumab as a monotherapy.
“Metastatic melanoma is one of the most aggressive forms of cancer with a historical five-year survival rate of less than ten percent in patients with distant metastasis. Results from these investigational studies showed a prolonged survival benefit with Yervoy at four and five years for some patients,” said Celeste Lebbe, MD, professor of Dermatology at Hôpital Saint-Louis in Paris, France and lead author of the five-year survival study in a statement. “These results add to the growing body of long-term survival data seen in some patients treated with Yervoy and further our understanding of the potential of this immunotherapy in the treatment of metastatic melanoma.”