Ability to project long-term response to treatment with abiraterone acetate + prednisone


A report published yesterday on the OncLive web site discusses a presentation by Dr. Howard Scher at the 2013 European Cancer Congress in Amsterdam. Dr. Scher reported that a panel of biomarkers could identify men with metastatic, castration-resistant prostate cancer (mCRPC) who were responding well or less well to treatment with abiraterone + prednisone.

According to the report, Dr. Scher provided data in his presentation to support the two following concepts:

  • The number of circulating tumor cells (CTCs) in combination with serum levels of lactate dehydrogenase (LDH) can predict how well abiraterone acetate + prednisone has worked at 12 weeks after initiation of therapy
  • If the combination of abiraterone acetate + prednisone has not provided a substantial clinical benefit at 12 weeks, no further improvement in patient outcome can reasonably be expected.

The data presented by Dr. Scher were based on a pre-specified, individual risk assessment of 711 patients with (we think) chemotherapy-naive  mCRPC who participated in the second major randomized Phase III clinical trial of abiraterone acetate + prednisone vs. a placebo + prednisone (the COU-AA-302 trial). Whether it was the COU-AA-302 trial or the COU-AA-301 trial in men who had previously received docetaxel-based chemotherapy is not clear from the report.

Dr. Scher is quoted as having said in an interview that

[T]he probability of being alive at 2 years was 46 percent for patients in a good risk category, while if patients were in a high-risk category at the same time point, the probability of being alive was 2 percent.

During the clinical trial, these 711 patients had a variety of markers measured on a regular basis, specifically including their CTC level (monthly), their LDH level, and their PSA level (only after 12 weeks). The patients were divided into three groups:

  • “High-risk” if their CTC count was ≥ 5 and their LDH level was  > 250 IU/l
  • “Intermediate-risk” if their CTC count was ≥ 5 but their LDH level was ≤ 250 IU/l
  • “Low-risk if their CTC count was ≤ 4 and their LDH level was within the normal range.

They then demonstrated that, at 12 weeks after initiation of treatment with abiraterone acetate:

  • 46 percent of patients with low-risk disease according to the above criteria were still alive after 2 years on treatment.
  • Just 2 percent of patients with high-risk disease were still alive after 2 years on treatment.

The authors applied the Prentice criteria in the assessment of whether this combination of biomarkers offered an accurate method to predict actual 2-year survival (as demonstrated in the individual trial results).

These data appear to provide us with a way to determine which patients should be maintained on abiraterone acetate for a period longer than 12 weeks and which patients should be advised to consider an alternative management strategy after such a time period. Dr. Scher was very clear about this in a second statement given during an interview, pointing out that the difference between 46 percent survival and 2 percent survival

… is a huge difference, and it’s telling us that the 12-week post-treatment measurement of this biomarker gives you a pretty good estimate of a patient’s prognosis. We would argue that if patients are still in a high-risk category at the 12-week point, physicians should consider doing something else.

2 Responses

  1. Thank you. I have a question. My friend has been on abiraterone for about a couple years now. What can we expect for him?

  2. Dear Samuel:

    We really have no clear idea yet what the upper limit is for good response to a drug like abiraterone acetate. If your friend is still responding well after 2 years on therapy, then all we can really say is “Good for him” and that we hope he goes on responding well for at least another 2 years, by which time we might have another breakthrough drug available for him to be able to use.

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