Early PSA measures not good guide in Cabazitaxel treatment for metastatic castrate resistant prostate cancer

[JimJimJimJim]

Jim Marshall (not a doctor) said …

In advanced prostate cancer your PSA is one of a number of indicators your doctor uses to watch your progress. However, it is not the only indicator, and stopping a treatment based solely on PSA can be a mistake for two drugs used to treat advanced prostate cancer.

 

In an earlier post Dr Judd Moul, an expert oncologist, advised that the drug Zytiga (abiraterone) remained effective after the PSA began to rise. He advised that Zytiga (abiraterone) treatment should not be stopped until all three of the following are true:

• PSA rises by 25% over baseline;

• AND scans of bone show things are worse;

• AND their doctor sees clinical progression (added pain is one indicator)

Keep Abiraterone going after PSA rises advises Dr Judd Moul

 

The paper below provides advice on the use of PSA for the use of Cabazitaxel for metastatic prostate cancer.

 

The advice is clear. Early changes in PSA when using Cabazitaxel are not a good indicator that the treatment is working.

 

Your doctor will be looking to other indicators (scans, pain, other symptoms) to rate your progress.

 

The drug treatment regime approved (and free on the Pharmaceutical Benefits Scheme (PBS) in Australia at the time of writing (November 2013) is:

• Taxotere (docetaxel) then
  
• Zytiga (abiraterone) then
  
• Cabazitaxel then
  
• Mitozantrone.
  

The first three drugs can extend life. Mitozantrone merely give symptom relief.

… end Jim

J Clin Oncol. 2013 Nov 1;31(31):3944-50. doi: 10.1200/JCO.2013.50.3201. Epub 2013 Oct 7.

Prostate-specific antigen changes as surrogate for overall survival in men with metastatic castration-resistant prostate cancer treated with second-line chemotherapy.

Halabi S, Armstrong AJ, Sartor O, de Bono J, Kaplan E, Lin CY, Solomon NC, Small EJ.

Source

Susan Halabi, Andrew J. Armstrong, Ellen Kaplan, Chen-Yen Lin, and Nicole C. Solomon, Duke University, Durham, NC; Oliver Sartor, Tulane University, New Orleans, LA; Johann de Bono, Royal Marsden Hospital, Sutton, United Kingdom; and Eric J. Small, University of California at San Francisco, San Francisco, CA.

Abstract

PURPOSE:

Prostate-specific antigen (PSA) kinetics, and more specifically a ≥ 30% decline in PSA within 3 months after initiation of first-line chemotherapy with docetaxel, are associated with improvement in overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC). The objective of this analysis was to evaluate post-treatment PSA kinetics as surrogates for OS in patients receiving second-line chemotherapy.

PATIENTS AND METHODS:

Data from a phase III trial of patients with mCRPC randomly assigned to cabazitaxel plus prednisone (C + P) or mitoxantrone plus prednisone were used. PSA decline (≥ 30% and ≥ 50%), velocity, and rise within the first 3 months of treatment were evaluated as surrogates for OS. The Prentice criteria, proportion of treatment explained (PTE), and meta-analytic approaches were used as measures of surrogacy.

RESULTS:

The observed hazard ratio (HR) for death for patients treated with C + P was 0.66 (95% CI, 0.55 to 0.79; P < .001). Furthermore, a ≥ 30% decline in PSA was a statistically significant predictor of OS (HR for death, 0.52; 95% CI, 0.43 to 0.64; P < .001). Adjusting for treatment effect, the HR for a ≥ 30% PSA decline was 0.50 (95% CI, 0.40 to 0.62; P < .001), but treatment remained statistically significant, thus failing the third Prentice criterion. The PTE for a ≥ 30% decline in PSA was 0.34 (95% CI, 0.11 to 0.56), indicating a lack of surrogacy for OS. The values of R(2) were < 1, suggesting that PSA decline was not surrogate for OS.

CONCLUSION:

Surrogacy for any PSA-based end point could not be demonstrated in this analysis. Thus, the benefits of cabazitaxel in mediating a survival benefit are not fully captured by early PSA changes.

PMID: 24101043

This extract can be found on http://PubMed.com, and is in the public domain.

On PubMed.com there will be a link to the full paper (often $30, sometimes free).

 

Any highlighting (except the title) is not by the author, but by Jim Marshall.

Jim is not a doctor.