No Activity With Olaparib After Failure of Systemic Therapy in CRC

Single-agent olaparib delivered after failure of standard systemic therapy did not demonstrate activity in patients with colorectal cancer.
Single-agent olaparib delivered after failure of standard systemic therapy did not demonstrate activity in patients with colorectal cancer.

Single-agent olaparib delivered after failure of standard systemic therapy did not demonstrate activity in patients with colorectal cancer, regardless of microsatellite status, according to a study published in The Oncologist.1

In an open-label, phase 2 trial, researchers led by Lawrence Leichman, MD, of the New York University Langone Medical Center tested olaparib in 33 patients with disseminated, measurable colorectal cancer who failed standard therapies and had centrally confirmed tumor MSI status.

Twenty patients were microsatellite stable, and 13 had high-level microsatellite instability. Primary end point was tumor response while secondary end points were safety/toxicity, progression-free survival, and overall survival.

Among the patients, all of whom received at least one 28-day cycle of olaparib, none had a complete or partial response. The most commonly reported treatment-related adverse events were nausea (48%), fatigue (36%), and vomiting (33%), and median progression-free survival for all patients was 1.84 months.

There were no statistically significant differences in median progression-free or overall survival for patients in the microsatellite stable group compared to those with high-level microsatellite instability.

“Future trials, testing PARP inhibitors in patients with colorectal cancer should focus on the use of DNA-damaging chemotherapy and/or radiation therapy, combined with PARP inhibitors, remembering the toxicity reported in the present study,” the authors concluded.

REFERENCE

1. Leichman L, Groshen S, O'Neil BH, et al. Phase II study of olaparib (AZD-2281) after standard systemic therapies for disseminated colorectal cancer [published online ahead of print January 19, 2016]. The Oncologist. doi:10.1634/theoncologist.2015-0319.

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