A phase II study of eribulin in recurrent or refractory osteosarcoma: A report from the Children's Oncology Group

Abstract

Background Patients with recurrent or refractory osteosarcoma have a poor prognosis with less than 30% surviving two years. Eribulin is a synthetic analog of halichondrin B, has a novel mechanism of action when compared with other microtubule inhibitors, and may have antitumor activity in osteosarcoma. Methods A prospective study was designed to assess the disease control success at four months and objective response rates in patients with recurrent or refractory osteosarcoma treated with eribulin. Eligible patients were between 12 and 50 years of age, had measurable tumor, and met standard organ function requirements. Patients were given eribulin 1.4 mg/m2/dose on days 1 and 8 of each 3‐week cycle for up to 24 months if there was no progressive disease. Response to therapy was assessed using RECIST 1.1 criteria after cycles 2 and 5 and every fourth cycle thereafter. Results Nineteen patients enrolled on the AOST1322 study. The median age of enrollment was 16 years (range, 12–25 years). Twelve patients were male and seven female. Eribulin was well tolerated, with neutropenia identified as the most common toxicity. The median progression‐free survival was 38 days and no patients reached the four‐month time point without progression. No objective responses were seen in any patient. Conclusion This study rapidly assessed the clinical activity of a novel agent in this patient population. Eribulin was well tolerated, but there were no patients who demonstrated objective response, and all patients had progression prior to four months.

A phase 1 study of eribulin mesylate (E7389), a novel microtubule‐targeting chemotherapeutic agent, in children with refractory or recurrent solid tumors: A Children's Oncology Group Phase 1 Consortium study (ADVL1314)

“…Eribulin was given at 1.4 mg/m 2 /dose on days 1 and 8 of a 21‐day cycle and was well tolerated, but failed to show activity in patients with recurrent osteosarcoma. No patient demonstrated objective response and all patients had progression prior to 4 months . Consistent with these data, none of our nine subjects with osteosarcoma achieved any observable benefit.…”

“…No patient demonstrated objective response and all patients had progression prior to 4 months . Consistent with these data, none of our nine subjects with osteosarcoma achieved any observable benefit.…”

Provocative questions in osteosarcoma basic and translational biology: A report from the Children's Oncology Group

“…88,89 Although numerous therapeutic strategies have some preclinical evidence supporting further investigation, very few have a level of evidence that would meet traditional standards for justifying a clinical trial. This has created a situation in which there are more patients who are interested in enrolling in clinical trials than there are trials available, as evidenced by the rapid accrual of recent trials that have far exceeded enrollment expectations.…”

“…Such efforts have long been hampered by the lack of an acceptable historical control. 88,89 Other emerging lines of work could significantly affect how we conduct clinical trials in OS. 86 This transition to a more relevant, easily measured efficacy threshold circumvents the problems inherent to the application of more widely used Cancer October 15, 2019 response measures inherent to OS.…”

“…Using these standards, trials can be conducted in under 3 years. 88,89 Other emerging lines of work could significantly affect how we conduct clinical trials in OS. For instance, Bayesian trial designs might have particular value in rapidly evaluating multiple treatments for rare tumors like OS.…”