ADT + bevacizumab as first-line treatment of recurrent prostate cancer

Data from a small, randomized, Phase II, clinical trial have suggested a possible role for bevacizumab (Avastin) in the treatment of men with recurrent prostate cancer along with androgen deprivation therapy (ADT).

McKay et al. report data from a study which enrolled men with recurrent prostate cancer after local treatment who had an increasing PSA level of ≤ 50 ng/ml and PSA doubling time of < 18 months. Patients also had to have either no metastases or low burden, asymptomatic metastases (lymph nodes < 3 cm and five or fewer bone metastases).

It appears (from the abstract and the trial protocol) that the patients were randomized to one or the other of two possible treatments:

  • ADT (using an LHRH agonist + bicalutamide) + bevacizumab for 6 months
  • ADT (using an LHRH agonist + bicalutamide) for 6 months

The randomization was 2:1, with twice as many patients randomized to the “+ bevacizumab” arm of the study. Treatment was given for just 6 months. The primary end point was PSA relapse-free survival (RFS). Relapse was defined as a PSA of > 0.2 ng/ml for primary prostatectomy patients or a PSA of > 2.0 ng/mL for primary radiation therapy patients. The trial protocol indicates that follow-up was for a maximum of 2 years.

Here are the study findings:

  • The trial enrolled 102 patients.
    • 66 patients received ADT + bevacizumab.
    • 36 received ADT alone.
  • Average (median) RFS times were
    • 13.3 months for patients treated with ADT + bevacizumab
    • 10.2 months for patients treated with ADT alone
    • Hazard ratio (HR) = 0.47; log-rank P = 0.002).
  • Hypertension was the most common adverse event in patients receiving ADT + bevacizumab (36 percent).

McKay et al. conclude that:

ADT combined with bevacizumab resulted in an improved RFS for patients with hormone-sensitive prostate cancer. Long-term follow-up is needed to determine whether some patients have a durable PSA response and are able to remain off ADT for prolonged periods. Our data provide rationale for combining vascular endothelial growth factor–targeting therapy with ADT in hormone-sensitive prostate cancer.

The “New” Prostate Cancer InfoLink is somewhat skeptical about this study and the resulting data. We consider that this trial is a test of a possible hypothesis that would need to be validated in much larger and longer trials before it should be considered as a serious clinical opportunity for patients. The hypothesis being tested is that some men with progressive disease (and a PSA doubling time of < 18 months) after first-line therapy could be put into remission with a short course of ADT + bevacizumab. But if such a therapy is only going to work for a maximum of 2 years, is this really long-term remission?

It is not at all clear from the abstract how many of the patients were actually good candidates for any form of ADT (with or without bevacizumab) to begin with. While such treatment may have been appropriate for the subset of patients who were failing after first-line radiation therapy, it is arguable that it would have been inappropriate for any of the patients who had progressive disease after first-line surgery since the current standard of care would be radiation therapy with or without ADT.

In addition, while there was apparently no sign of any of the really serious side effects of bevacizumab observed in this trial, we know that such serious side effects occur in some patients, and can include gastrointestinal perforations, wounds that don’t heal, and serious bleeding events.

There have been numerous trials of bevacizumab now executed in the treatment of progressive and late stage prostate cancer. As far as we can tell, the beneficial effects of bevacizumab in combination with other agents appear to be very limited in the management of prostate cancer. Conversely, the risk for side effects of treatment have been significant. Even hypertension in 36 percent of the men treated with bevacizumab in this trial presents a problematic risk level.

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