BACKGROUND: Preclinical studies have documented antitumor activity of PARP 
inhibition both in vitro and in vivo, against Ewing sarcoma cells. This study 
aimed to translate that observation into a clinical trial to assess the efficacy 
and tolerability of olaparib, a PARP inhibitor, in patients with advanced Ewing 
sarcoma (EWS) progressing after prior chemotherapy.
METHODS: In this nonrandomized phase II trial, adult participants with 
radiographically measureable metastatic EWS received olaparib tablets, 400 mg 
orally twice daily, until disease progression or drug intolerance. Tumor 
measurements were determined by CT or MRI at 6 and 12 weeks after starting 
olaparib administration, and then every 8 weeks thereafter. Tumor response 
determinations were made according to RECIST 1.1, and adverse event 
determinations were made according to CTCAE, version 4.0. A total of 22 
participants were planned to be enrolled using a conventional 2-step phase II 
study design. If no objective responses were observed after 12 participants had 
been followed for at least 3 months, further accrual would be stopped.
RESULTS: 12 participants were enrolled, and all were evaluable. There were no 
objective responses (PR/CR), 4 SD (duration 10.9, 11.4, 11.9, and 17.9 wks), and 
8 PD as best response. Of the SD, 2 had minor responses (-9% and -11.7% by 
RECIST 1.1). The median time to disease progression was 5.7 weeks. Further 
enrollment was therefore discontinued. No significant or unexpected toxicities 
were observed with olaparib, with only a single case each of grade 3 anemia and 
grade 3 thrombocytopenia observed.
CONCLUSIONS: This study is the first report of a prospective phase II trial to 
evaluate the safety and efficacy of a PARP inhibitor in patients with advanced 
Ewing sarcoma after failure of standard chemotherapy. Olaparib administration 
was safe and well tolerated when administered to this small heavily pre-treated 
cohort at the 400 mg BID dose, although the median duration of dosing was for 
only 5.7 weeks. No significant responses or durable disease control was seen, 
and the short average interval to disease progression underscores the 
aggressiveness of this disease. Other studies to combine cytotoxic chemotherapy 
with PARP inhibition in EWS are actively ongoing.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01583543.