Related Experiment Video
Updated: Apr 21, 2026
A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate
Published on: May 3, 2021
Phase II study of olaparib in patients with refractory Ewing sarcoma following failure of standard chemotherapy
Edwin Choy1, James E Butrynski, David C Harmon
1Division of Hematology Oncology, Massachusetts General Hospital, Boston, MA, USA. echoy@mgh.harvard.edu.
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.
Insights
Olaparib, a PARP inhibitor, showed no significant efficacy in advanced Ewing sarcoma patients. The drug was safe and well-tolerated, but did not provide durable disease control.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Preclinical studies indicated that PARP inhibition has antitumor activity against Ewing sarcoma cells.
- This study aimed to clinically evaluate olaparib, a PARP inhibitor, in advanced Ewing sarcoma (EWS) patients who had progressed after chemotherapy.
Purpose of the Study:
- To assess the efficacy and tolerability of olaparib in patients with advanced Ewing sarcoma.
- To determine if olaparib could provide clinical benefit in a heavily pre-treated patient population.
Main Methods:
- A nonrandomized phase II trial enrolled adult patients with measurable metastatic EWS.
- Patients received olaparib 400 mg orally twice daily until disease progression or intolerance.
- Tumor response was assessed using RECIST 1.1 criteria, and adverse events were graded per CTCAE v4.0.
Main Results:
- Twelve patients were enrolled and evaluable; no objective responses (PR/CR) were observed.
- Four patients had stable disease (SD) with durations ranging from 10.9 to 17.9 weeks.
- The median time to disease progression was 5.7 weeks, leading to discontinuation of further enrollment.
Conclusions:
- Olaparib was safe and well-tolerated in this cohort of advanced Ewing sarcoma patients.
- The study did not demonstrate significant responses or durable disease control with olaparib monotherapy.
- The rapid progression highlights the aggressive nature of advanced EWS; further combination studies are ongoing.
Related Concept Videos
02:56Treatment Resistent Cancers
02:56Treatment Resistant Cancers