Given all the newly approved drugs available to us to treat advanced prostate cancer there now are many questions about the optimal sequencing of these drugs and whether earlier use of one causes cross-resistance to another.
Recently, it was reported that chemotherapy with docetaxel is inactive in men with metastatic castrate resistant prostate cancer (mCRPC) who did not have a at least a 50% PSA decline while on abiraterone (Zytiga) (Ann Oncol 2012; 23(11):2943-7).
To see if these results might be replicated researchers evaluated the activity of docetaxel in men with mCRPC who had previously received Zytiga.
Cancer registries at two Canadian centers were used to identify subjects. The outcomes from docetaxel treatment were compared between Zytiga responders (those who had a greater than 50% PSA decrease with prior Zytiga exposure) and Zytiga non-responders (those men who had a less than 50% PSA decrease with prior Zytiga exposure).
Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method.
Of 40 eligible men, 14 (35%) were classified as Zytiga responders and 26 (65%) as non-responders (including 16 men who had no PSA decline on Zytiga). The median number of cycles of docetaxel (chemotherapy) administered to Zytiga responders and non-responders was 6 (range: 1-10) and 4 (range: 1-13) respectively.
Thirty (75%) of the men had also received docetaxel prior to Zytiga. Notably, among 39 of the men evaluable for PSA response, no difference was seen in the proportion of Zytiga responders and non-responders who had PSA falls greater than 50%.
Their analysis of survival outcomes from date of initiation of docetaxel also revealed similar median PFS (p=0.54; log-rank) and median OS (p=0.93; log-rank) in both groups.
Now the translation: Men in this study did not have a PSA response difference regardless if they were Zytiga responders or if they were non-responders. These data suggest that the anti-tumor activity of docetaxel chemotherapy in men with mCRPC may be independent of prior responses to Zytiga and that chemotherapy is still a therapeutic option in men who do not respond to Zytiga.
J Clin Oncol 32, 2014 (suppl 4; abstr 97); Arun Azad, Renee Lester, Daniel Yick Chin Heng, Bernhard J. Eigl, Kim N. Chi.
Joel T. Nowak, M.A., M.S.W.