Busulfan/Melphalan Associated With Longer Survival in High-Risk Ewing Sarcoma

CHICAGO-Busulfan/melphalan high-dose chemotherapy consolidation (BuMel) is associated with better survival vs vincristine, actinomycin-D, and ifosfamide (VAI) among patients with localized high-risk Ewing sarcoma, according to findings from the randomized EURO-EWING 99-R2 study, presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 3–7 in Chicago (abstract 11000).

“BuMel conferred improvement in EFS [event-free survival] and OS [overall survival] with acceptable toxicity for patients with localized Ewing sarcoma and poor histological response to chemotherapy or large tumor volume unresected,” reported lead study author Jeremy Whelan, MD, of the University College London Hospitals in London. “It should be considered as a standard of care for this group of patients with localized high-risk Ewing sarcoma and no contraindication to BuMel.”

The study randomly assigned 216 eligible patients to undergo VAI (n = 107) or BuMel (n = 109). Concerns about busulfan’s interaction with radiation limited the number of patients who were eligible for this study, Whelan said. “Some patients requiring radiation therapy to the primary site were excluded to avoid excess organ toxicity,” he explained.

Study recruitment was “prolonged” (2000–2013), Whelan noted. “Approximately half of eligible patients participated in the randomized trial,” he said.

In the intent-to-treat population, BuMel’s 3-year EFS was superior to VAI (67% vs 53%; hazard ratio [HR], 0.64 [95% CI, 0.43–0.94]; P = .024). The results were stable in per-protocol analyses excluding patients with major treatment modification (HR, 0.55 [95% CI, 0.36–0.85]; P = .007) and patients with major treatment modification plus ineligible patients (HR, 0.57 [95% CI, 0.37–0.88]; P = .01). Subgroup analyses revealed no major heterogeneity of BuMel associations.

BuMel was also associated with better 3-year OS (78% vs 70%; HR, 0.60 [95% CI, 0.39–0.92]; P = .019).

Acute toxicities were “expected and manageable in most cases,” Whelan noted, adding that data about long-term toxicities are not yet available. BuMel was associated with increased acute gastrointestinal tract toxicity, liver toxicity, and infection.