AR-V7 and resistance to treatment with enzalutamide, abiraterone


We have previously commented on early reports that prostate cancer patients carrying the androgen receptor subtype known as AR-V7 (the “isoform” encoded by splice variant 7) exhibit a high level of resistance to treatment with both enzalutamide (Xtandi) and abiraterone acetate (Zytiga).

The full details of the data from these studies have now been published by Antonarakis et al. in this week’s issue of the New England Journal of Medicine.

Basically, Antonarakis et al. report that they studied data from 31 men who had been treated with enzalutamide and another 31 who had been treated with abiraterone acetate. Here are their core findings:

  • Among the men treated with enzalutamide
    • 12/31 (39 percent) had detectable AR-V7 in circulating tumor cells.
    • Compared to AR-V7-negative patients, the AR-V7-positive patients had
      • Lower PSA response rates (0 vs. 53 percent, P = 0.004)
      • Shorter average (median) PSA-based progression-free survival times (1.4 vs. 6.0 months; P < 0.001),
      • Shorter average (median) clinical or radiographic progression-free survival times (2.1 vs. 6.1 months; P < 0.001)
      • Shorter average (median) overall survival times (5.5 months vs. not reached; P = 0.002)
  • Among the men treated with abiraterone acetate
    • 6/31 (19 percent) had detectable AR-V7 in circulating tumor cells
    • Compared to AR-V7-negative patients, the AR-V7-positive patients had
      • Lower PSA response rates (0 vs. 68 percent, P = 0.004)
      • Shorter average (median) PSA-based progression-free survival times (1.3 months vs. not reached; P < 0.001),
      • Shorter average (median) clinical or radiographic progression-free survival times (2.3 months vs. not reached; P < 0.001)
      • Shorter average (median) overall survival times (10.6 months vs. not reached; P = 0.006)

Testing for the presence of the AR-V7 isoform of the androgen receptor was carried out using a sophisticated biochemical test known as a quantitative reverse-transcriptase-polymerase chain reaction (RT-PCR) assay. Availability of this test is currently limited, and so the short-term, clinical implications of these data are not currently known. Since both of these drugs are extremely expensive, any patient considering treatment with either enzalutamide or abiraterone acetate might be wise to get pre-tested for the presence of the AR-V7 isoform. However, before such a policy can be fully implemented, we probably need to see data from larger prospective studies to confirm these early data, and regular pre-testing would necessitate ease of access to the appropriate RT-PCR assay test for clinicians working in community settings.

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