The addition of palifosfamide to doxorubicin did not improve PFS in patients with metastatic soft tissue sarcoma, according to results of the randomized controlled phase 3 PICASSO III trial.
“Treatment of the diverse group of mesenchymal neoplasms known as soft tissue sarcomas remains challenging, with few effective treatments for metastatic disease,” Christopher W. Ryan, MD, clinical researcher at Oregon Health & Science University, and colleagues wrote. “More than 40 years after the first reports of activity in sarcoma, doxorubicin is still the standard first-line treatment for most patients.”
A phase 2 trial of doxorubicin in combination with palifosfamide (Zymafos, Ziopharm Oncology) improved PFS compared with single-agent doxorubicin.
Ryan and colleagues randomly assigned 447 patients with metastatic soft tissue sarcoma to 21-day cycles of IV doxorubicin (75 mg/m2 on day 1) plus IV palifosfamide (150 mg/m2 on days 1-2; n = 226) or plus placebo (n = 221). Treatment continued for up to six cycles.
PFS served as the primary endpoint. Secondary endpoints included OS, overall response rate and safety.
Median follow-up was 11 months for patients assigned palifosfamide and 11.5 months for patients assigned placebo.
The researchers observed no significant PFS differences with doxorubicin plus palifosfamide or plus placebo (median, 6 months vs. 5.2 months; HR = 0.86; 95% CI, 0.68-1.08).
Patients assigned placebo achieved a slightly longer OS than those assigned palifosfamide (median, 16.9 months vs. 15.9 months; HR = 1.05; 95% CI, 0.79-1.39).
Patients assigned palifosfamide had better response rates (P = 0.47); however, median duration of response did not differ between groups (median, 4.3 months vs. 4.6 months).
Palifosfamide treatment resulted in a higher incidence of grade 3 or grade 4 adverse events (63.6% vs. 50.9%; P = .0075), including a significantly higher rate of febrile neutropenia (21.4% vs. 12.6%; P = .015).
The data-monitoring committee recommended the study’s early termination. Palifosfamide is no longer being developed as a treatment for patients with metastatic soft tissue sarcoma, according to a press release from the drug’s manufacturer.
“This phase 3 trial was unable to confirm the results of a previous, nonblinded, randomized phase 2 trial that had shown a longer-duration PFS for doxorubicin plus palifosfamide compared with doxorubicin alone,” Ryan and colleagues wrote. “This study represents one of the largest international efforts among sarcoma centers to date. The median PFS of 5.2 months and OS of nearly 17 months with doxorubicin should serve as a reference in the design of future studies in the first-line treatment of metastatic soft tissue sarcoma." – by Cameron Kelsall
Disclosure: Ryan reports consultant roles with Eisai, EMD Serono, Exelixis, Janssen Oncology, Karyopharm Therapeutics, Onyx and Pfizer, as well as institutional research funding from multiple pharmaceutical companies, including Ziopharm Oncology. Please see the full study for a list of all other researchers’ relevant financial disclosures.