The explosion of new therapies for men with metastatic castration resistant prostate cancer (mCRPC) raises serious questions about the optimal sequencing of these new treatments as well as whether cross-resistance occurs between these drugs.
It was recently reported that chemotherapy with docetaxel (D) is not effective in in men who did not have a ? 50% PSA decline on prior Zytiga treatment (Ann Oncol 2012; 23(11):2943-7). To evaluate this, Azad etal. looked at the activity of D in men with mCRPC who had previously taken Zytiga.
They drew their subject pool from two Canadian cancer registries.
Outcomes from D treatment were compared between Zytiga responders (? 50% PSA decrease with prior Zytiga) and Zytiga non-responders (< 50% PSA decrease with prior Zytiga). Progression-free survival (PFS) (Prostate Cancer Working Group 2 criteria) and overall survival (OS) were estimated using the Kaplan-Meier method.
In the anaylisis they had 40 eligible men, 14 (35%) were classified as Zytiga responders and 26 (65%) as Zytiga non-responders (including 16 men who had no PSA decline on Zytiga). The median number of cycles of D administered to Zytiga responders and non-responders was 6 (range: 1-10) and 4 (range: 1-13) respectively. Thirty (75%) men had also received D prior to Zytiga. Notably, among 39 men evaluable for PSA response, no difference was seen in the proportion of Zytiga responders and non-responders who had PSA falls ? 50% (p=0.72; Fisher’s exact test) or ? 30% (p=0.75; Fisher’s exact test) on D.
Analysis of the overall survival which went from the date of initiation of D also revealed similar median PFS (p=0.54; log-rank) and median OS (p=0.93; log-rank) in both groups.
They concluded thatPSA response rates to D did not differ between Zytiga responders and non-responders. These data suggest that the anti-tumor activity of D in mCRPC may be independent of prior response to Zytiga and that chemotherapy is still a therapeutic option in men who do not respond to Zytiga.
Given the contradiction of the data additional studies in cross resistance of Zytiga and D as well as additional studies evaluating the optimal sequencing of Zytiga and D in mCRPC are warranted.
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.
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