In the phase III PICASSO III trial reported in the Journal of Clinical Oncology, Christopher W. Ryan, MD, of Oregon Health & Science University, and colleagues found that adding palifosfamide to doxorubicin did not prolong progression-free survival among patients with metastatic soft-tissue sarcoma. Palifosfamide is the active metabolite of ifosfamide.
In the double-blind trial, 447 patients with no prior treatment for metastatic disease from 113 sites in 19 countries were randomized between August 2010 and July 2012 to receive palifosfamide at 150 mg/m2 on days 1 to 3 plus doxorubicin at 75 mg/m2 on day 1 (n = 226) or doxorubicin plus placebo (n = 221) once every 21 days for up to 6 cycles. The primary endpoint was progression-free survival on independent radiologic review in the intent-to-treat population.
Survival and Toxicity
The data monitoring committee recommended continuation of the study after each of two interim analyses for progression-free survival. The study database was frozen in March 2013, after the progression-free survival target of 330 events had been reached. The data monitoring committee recommended terminating the study upon review of these data.
Median follow-up was 11.0 months in the palifosfamide/doxorubicin group and 11.5 months in the doxorubicin group. Median progression-free survival was 6.0 months vs 5.2 months (hazard ratio [HR] = 0.86, P = .19). An overall survival analysis performed after 59% of the total targeted overall survival events showed median overall survival of 15.9 months vs 16.9 months (HR = 1.05, P = .74). No additional overall survival data were collected after study termination, and additional planned overall survival analyses were not performed.
The incidence of grade 3 or 4 adverse events was higher in the palifosfamide/doxorubicin group (63.6% vs 50.9%), including higher rates of neutropenia (21.4% vs 12.6%) and anemia (16.8% vs 8.9%). The most common adverse events of any grade were alopecia, nausea, and fatigue in both groups.
The investigators concluded: “No significant difference in [progression-free survival] was observed in patients receiving doxorubicin plus palifosfamide compared with those receiving doxorubicin plus placebo. The observed median [progression-free survival] and overall survival in this large, international study can serve as a benchmark for future studies of doxorubicin in metastatic soft tissue sarcoma.”
The study was supported by ZIOPHARM Oncology. ■