Phase II results released for another PARP Inhibitor

July 6, 2010

In a small Phase II study published in The Lancet and funded by drug maker AstraZeneca, another PARP inhibitor, olaparib, appears to work as predicted, at least in some patients. 

The drug, an orally active poly(ADP-ribose) polymerase (PARP) inhibitor, appears to have caused cancer cell death in a "proof-of-concept trial" in women with BRCA1 and BRCA2 mutations and metastatic breast cancer.  Twenty-seven women with confirmed BRCA mutations and metastatic breast cancer were given oral olaparib at the maximum tolerated dose (400 mg twice daily), and a second group of 27 women was given a lower dose (100 mg twice daily). Patients had been given a median of three previous chemotherapy regimens. An objective response (a decrease in tumor size based on standard criteria) was seen in 11 of the 27 patients in the maximum dose group, and six of the 27 patients in the lower dose group.  Most high grade adverse events were seen in the high dose group: fatigue 4/27 with grade 3 or 4, nausea 4/27 with grade 3 or 4, vomiting 3/27 with grade 3 or 4, and anemia 3/27 with grade 3 or 4.

The concept is that olaparib, and other PARP inhibitors, cause cancer cell death when BRCA mutations are present in tumors.  The drugs inhibit a protein called poly(ADP-ribose) polymerase (PARP). Both PARP and the BRCA proteins are involved in DNA repair. Cells seem to be able to do without one or the other, but the theory is that inhibiting PARP in a tumor that lacks a BRCA gene is too much for the cells, and will cause them to die.

Further results from larger, more advanced studies will be needed to evaluate the impact of these drugs on overall survival.  Read the Advocate Reports from ASCO on PARP Inhibitors.