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New AR-V7 test helps choose best treatment to start for metastatic castrate resistant prostate cancer

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Jim Marshall (not a doctor) said ...

When hormone therapy (ADT) is no longer enough to control a man's disease, a stronger drug is added to his treatment.

 

Doctors may choose:

  • a super-hormone like Zytiga (abiraterone) or Xtandi (enzalutamide); or
  • a chemotherapy drug like Taxotere (docetaxel)

 

But which will give the longest survival?

Before starting treatment, these researchers:

  • took blood samples.
  • separated cancer cells that were in the blood. 
  • tested to see whether the nucleus (centre) of these cancer cells showed the presence of a protein called AR-V7.

 

Half the men started on a super-hormone, the other half on chemotherapy.

 

If a man did have AR-V7 in his cancer cell nucleus he was called AR-V7-positive, if not, AR-V7-negative.

 

Men who had AR-V7 lived longer if they started on chemotherapy rather than a super-hormone.

 

Men who did not have AR-V7 lived longer if they started on a super-hormone rather than chemotherapy.

 

There are a number of different AR-V7 tests available, and different studies have shown variable results.

But this study used a specially developed test in the hope it was more accurate to look at where in the cancer cell the AR-V7 occurred.

 

A few days ago researchers have just published their first results in a respected journal. Before this becomes standard practice doctors will have to accept that these results are correct, and that the differences reported are big enough to matter.

Then the test will need to pass regulatory bodies like the FDA (Food and Drug Administration) in the USA and the TGA (Therapeutic Goods Administration) in Australia. Finally, it will be up to insurers to decide if the price the company sets for the test is worth the benefit.

 

So, not anytime yet.

Meanwhile, less accurate AR-V7 tests are available around the world, and your oncologist may have to rely on these for now.

... end Jim

 

JAMA Oncol. 2018 Jun 28. doi: 10.1001/jamaoncol.2018.1621. [Epub ahead of print]

Assessment of the Validity of Nuclear-Localized Androgen Receptor Splice Variant 7 in Circulating Tumor Cells as a Predictive Biomarker for Castration-Resistant Prostate Cancer.

Scher HI1,2, Graf RP3, Schreiber NA1, Jayaram A4,5, Winquist E6,7, McLaughlin B1, Lu D3, Fleisher M8, Orr S3, Lowes L6,7, Anderson A3, Wang Y3, Dittamore R3, Allan AL6,7, Attard G4,5, Heller G9.

Author information

Abstract

IMPORTANCE:

A blood test to determine whether to treat patients with metastatic castration-resistant prostate cancer (mCRPC) with an androgen receptor signaling (ARS) inhibitor or taxane is an unmet medical need.

 

OBJECTIVE:

To determine whether a validated assay for the nuclear-localized androgen receptor splice variant 7 (AR-V7) protein in circulating tumor cells can determine differential overall survival among patients with mCRPC treated with taxanes vs ARS inhibitors.

 

DESIGN, SETTING, AND PARTICIPANTS:

This blinded correlative study conducted from December 31, 2012, to September 1, 2016, included 142 patients with histologically confirmed mCRPC and who were treated at Memorial Sloan Kettering Cancer Center, The Royal Marsden, or the London Health Sciences Centre. Blood samples were obtained prior to administration of ARS inhibitors or taxanes as a second-line or greater systemic therapy for progressing mCRPC.

 

MAIN OUTCOMES AND MEASURES:

Overall survival after treatment with an ARS inhibitor or taxane in relation to pretherapy AR-V7 status.

 

RESULTS:

Among the 142 patients in the study (mean [SD] age, 69.5 [9.6] years), 70 were designated as high risk by conventional prognostic factors. In this high-risk group, patients positive for AR-V7 who were treated with taxanes had superior overall survival relative to those treated with ARS inhibitors (median overall survival, 14.3 vs 7.3 months; hazard ratio, 0.62; 95% CI, 0.28-1.39; P = .25). Patients negative for AR-V7 who were treated with ARS inhibitors had superior overall survival relative to those treated with taxanes (median overall survival, 19.8 vs 12.8 months; hazard ratio, 1.67; 95% CI, 1.00-2.81; P = .05).

 

CONCLUSIONS AND RELEVANCE:

This study suggests that nuclear-localized AR-V7 protein in circulating tumor cells can identify patients who may live longer with taxane chemotherapy vs ARS inhibitor treatment.

 

PMID: 29955787

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