I have written a lot about how we need more data about the many new drugs we have to treat men with advanced prostate cancer.  The many questions that continue to swirl around us pertain to the development of cross resistance (taking one drug causes another to not work) between these new drugs, knowing the best order to take these drugs (sequencing), knowing what drugs might work and knowing when a drug is working and or has stopped working.

To work towards answering the question about when enzalutamide (Xtandi) might work for an individual researchers have performed an evaluation of Xtandi’s effects on cancer and on androgens in blood and bone marrow, as well as associate these with clinical observations.

In a prospective phase 2 study, 60 men with metastatic castrate resistant prostate cancer (mCRPC) and bone metastases were given Xtandi as well as bone marrow biopsies before treatment and at 8 weeks after beginning treatment.

They found that the median time to treatment discontinuation was 22 weeks and that twenty-two (37%) of the men exhibited primary resistance to Xtandi (discontinuing treatment within 4 months). They also found that the maximal prostate-specific antigen (PSA) decline of greater or equal to 50% and greater than or equal to 90% occurred in 27 men (45%) and 13 men (22%) respectively.

They found that the presence of an ARV7 variant (Androgen receptor splice variant-7 is a truncated form of the androgen receptor that lacks the ligand-binding domain).was associated with primary resistance to Xtandi (p=0.018).

Because of the limited numbers of men in the study, to be on the safe side additional validation of these findings need be performed.  However, if you are having difficulty in deciding if Xtandi is your next best choice for a treatment you should discuss this data with your doctor to see if it might make sense for you to see if you have a significant presence of ARV7.

Eur Urol. 2014 May 29. pii: S0302-2838(14)00415-1. doi: 10.1016/j.eururo.2014.05.005; Efstathiou E, Titus M, Wen S, Hoang A, Karlou M, Ashe R, Tu SM, Aparicio A, Troncoso P, Mohler J, Logothetis C

PubMed Abstract
PMID: 24882673

Joel T. Nowak, M.A., M.S.W.