Eribulin Improves Overall Survival vs Dacarbazine in Advanced Liposarcoma or Leiomyosarcoma
In a phase III trial reported in The Lancet, Schöffski et al found that eribulin improved overall survival vs dacarbazine in patients with advanced or metastatic soft-tissue sarcoma who had received at least two prior systemic treatments for advanced disease. Outcome in the subgroup with liposarcoma led to U.S. Food and Drug Administration (FDA) approval of eribulin for patients with unresectable or metastatic liposarcoma who had received an anthracycline-containing regimen.
Study Details
In this open-label trial, 452 patients aged ≥ 18 years from 110 sites in 22 countries with intermediate- or high-grade advanced liposarcoma or leiomyosarcoma were randomized between March 2011 and May 2013 to receive eribulin at 1.4 mg/m² intravenously (IV) on days 1 and 8 (n = 228) or dacarbazine at 850 mg/m², 1,000 mg/m², or 1,200 mg/m² IV according to center and clinician discretion on day 1 every 21 days until disease progression. The primary endpoint was overall survival in the intent-to-treat population.
In the entire patient population, median age was 56 years (range = 24–83 years), 67% were female, 73% were white, Eastern Cooperative Oncology Group (ECOG) performance status was 0 for 44% and 1 for 53%, and 47% had received at least two prior systemic therapies. Geographic region was the United States or Canada for 38% in both groups; western Europe, Australia, or Israel for 46% to 47%; and eastern Europe, Latin America, or Asia for 15% in both. Diagnosis was leiomyosarcoma for 152 patients in the eribulin group (67%) and 145 in the dacarbazine group (65%) and liposarcoma for 75 (33%) and 78 (35%), respectively.
Among patients with liposarcoma, median age was 55 years (range = 32–83 years); 62% were male; 72% were white; ECOG performance status was 0 for 41% and 1 for 53%; 44% had received at least two prior therapies; and histologic subtypes were dedifferentiated in 45%, myxoid/round cell in 37%, and pleomorphic in 18%.
Overall Survival
Among all patients, median overall survival was 13.5 months (95% confidence interval [CI] = 10.9–15.6 months) in the eribulin group vs 11.5 months (95% CI = 9.6–13.0 months) in the dacarbazine group (hazard ratio [HR] = 0.77, P = .0169). Median progression-free survival was 2.6 months (95% CI = 1.9–2.8 months) vs 2.6 months (95% CI = 1.8–2.7 months; HR = 0.88, P = .23).
Subgroup analysis showed that a significant effect of eribulin on overall survival was limited to patients with liposarcoma; among these patients, median overall survival was 15.6 months (95% CI = 10.2–18.6 months) vs 8.4 months (95% CI = 5.2–10.1 months), with a hazard ratio of 0.51 (95% CI = 0.35–0.75). The authors noted that “[the] study was not powered to draw definitive conclusions from such subgroup analyses. Among patients with leiomyosarcoma, median overall survival was 12.7 months (95% CI = 9.8–14.8 months) vs 13.0 months (95% CI = 11.3–15.1 months), with a hazard ratio of 0.93 (95% CI = 0.71–1.20).
Use of post-study chemotherapy was similar in the two groups (69% vs 63%), except for greater use of dacarbazine in the eribulin group (34% vs 8%), as was post-study use of surgery (16% vs 17%) and radiotherapy (23% vs 20%).
Adverse Events
Grade ≥ 3 adverse events were more common in the eribulin group (67% vs 56%), including neutropenia (35% vs 16%) and leukopenia (10% vs 5%). Grade ≥ 3 anemia (12% vs 7%) and thrombocytopenia (15% vs < 1%) were more common in the dacarbazine group. Adverse events led to dose interruption in 33% vs 32% of patients, dose reduction in 26% vs 14%, and treatment discontinuation in 8% vs 5%.
A total of 13 patients died of treatment-emergent adverse events, including 10 (4%) in the eribulin group and 3 (1%) in the dacarbazine group. Of them, one death in the eribulin group, due to neutropenic sepsis, was considered possibly related to study treatment by the investigators. Another death in the eribulin group, due to septic shock, was considered possibly related to treatment by the trial sponsor but not by the investigators.
The investigators concluded: “Overall survival was improved in patients assigned to eribulin compared with those assigned to an active control, suggesting that eribulin could be a treatment option for advanced soft-tissue sarcoma.”
The study was funded by Eisai.
Patrick Schöffski, MD, of the University Hospitals Leuven, Leuven Cancer Institute, is the corresponding author of The Lancet article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
