Factors in the sequencing of late-stage prostate cancer treatments

A paper in the International Journal of Cancer offers information on the sequencing of cabazitaxel (CAB) and abiraterone acetate (ABI) in men with metastatic, castration-resistant prostate cancer (mCRPC) who have already progressed after treatment with docetaxel.

The co-called cabazitaxel and abiraterone sequential treatment (CAST) study was based on a retrospective analysis of data from men with docetaxel-resistant mCRPC who started on either CAB or ABI prior to December 2012 at 12 institutions in The Netherlands.

The primary outcome of the CAST study was overall survival; secondary outcomes included progression-free survival (PFS), biochemical progression-free survival (bPFS), and best clinical and PSA response.

Here are the core results of the study by Wissing et al.:

  • 63/132 patients were treated with CAB, then ABI before July 10, 2013.
  • 69/132 patients were treated with ABI, then CAB before July 10, 2013.
  • Average (median) overall survival was
    • 19.1 months for the CAB-ABI patients.
    • 17.0 months for the ABI-CAB patients.
    • This difference was not statistically significant (p = 0.369).
  • Average (median) PFS was
    • 8.1 months for the CAB-ABI patients.
    • 6.5 months for the ABI-CAB patients.
    • This difference was statistically significant (p = 0.050).
  • Average (median) bPFS was
    • 9.5 months for the CAB-ABI patients.
    • 7.7 months for the ABI-CAB patients.
    • This difference was also statistically significant (p = 0.024).
  • There were minor differences in toxicities based on therapy sequence.
    • Toxicity from cabazitaxel could be severe.
    • Toxicity from abiraterone acetate was milder.

This retrospective analysis suggests that:

  • Primary progression on either cabazitaxel or abiraterone did not preclude a response to the other agent.
  • Tumor response to each agent, but particularly to cabazitaxel, was lower when the agent was administered as higher-line therapy.

In other words, giving cabazitaxel prior to abiraterone acetate has a very slightly greater benefit in terms of progression-free and biochemical progression-free survival, but a greater risk for earlier adverse events. Conversely, giving abiraterone acetate prior to cabazitaxel has less benefit in terms of these measure of survival, but less risk for the early onset of adverse events.

As we have seen many times before in the management of prostate cancer, there is no definitive evidence that giving these two drugs in a particular order is beneficial. The real question appears to be the individual patient’s perspective on quality as opposed to quantity of life.

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