June 22, 2021

Treating metastatic prostate cancer

An indirect comparative effectiveness study using published data suggests that the targeted therapy olaparib should be re-evaluated for treating metastatic prostate cancer.

by Leigh MacMillan

The role of olaparib in treating men with metastatic castration-resistant prostate cancer (mCRPC) should be reconsidered, a new report in JAMA Network Open suggests. 

Christopher Wallis, MD, PhD, and colleagues conducted an indirect comparative effectiveness study of olaparib (an inhibitor of the DNA repair enzyme PARP) versus cabazitaxel in men with mCRPC using previously published data from the PROfound and CARD trials. They took advantage of the fact that both trials used a similar comparator group (re-challenge with novel androgen axis signaling inhibitors). 

PROfound included 387 patients with mCRPC who had variants in one of 15 genes involved in homologous recombination DNA repair (HRR). CARD included 255 mCRPC patients.   

In the indirect comparison, olaparib was associated with superior radiographic progression-free survival (rPFS) only for patients with mutations in BRCA1, BRCA2 or ATM genes. In patients with 12 other HRR gene variants, cabazitaxel was 83% more likely to result in superior rPFS. There was no difference in overall survival for patients treated with olaparib and cabazitaxel across any tested subgroup.  

The authors note that numerous active studies will aid in reassessing national guidelines for the use of PARP inhibitors in mCRPC.