STRIVE trial again shows benefits to enzalutamide vs. bicalutamide

Earlier this year results from the TERRAIN trial reported that adding enzalutamide (Xtandi) to LHRH agonist therapy was more effective than adding the antiandrogen bicalutamide in men with metastatic, castration-resistant prostate cancer ( M1 CRPC).

Now, at the annual meeting of the American Urological Association (AUA), the STRIVE trial has exhibited a similar set of results in men with both M1 and M0 CRPC.

In a late-breaking abstract Penson et al. (abstract no. PII-LBA10) have reported the following:

  • 396 men with either M0 or M1 CRPC were enrolled in this randomized Phase II trial.
    • 198 patients were randomized to treatment with enzalutamide 160 mg/day (in addition to continuing LHRH agonist therapy).
    • 198 patients were randomized to treatment with bicalutamide 50 mg/day (in addition to continuing LHRH agonist therapy).
  • Baseline characteristics were comparable between the two groups of patients.
  • The median age of all patients was 73 years and their median baseline PSA at study entry was 12 ng/ml.
  • Median time on treatment was
    • 14.7 months for men randomized to treatment with enzalutamide
    • 8.4 months for men randomized to treatment with bicalutamide
  • Median progression-free survival was
    • 19.4 months for men randomized to treatment with enzalutamide
    • 5.7 months for men randomized to treatment with  bicalutamide
  • Enzalutamide also demonstrated greater effectiveness than bicalutamide in terms of radiographic progression-free survival and time to PSA progression.
  • Furthermore, enzalutamide demonstated greater effectiveness that bicalutamide in the M0 and the M1 patients.
  • Serious adverse events cardiac adverse events of Grade 3 or higher were reported to be similar on the two different agents.
  • One seizure was reported in a patient treated with enzalutamide.
  • Adverse events that occurred in > 10 percent of patients and that were reported more frequently in men treated with enzalutamide compared to bicalutamide were
    • Fatigue (in 37.6 vs 28.3 percent)
    • Back pain (in 17.8 vs 15.7 percent)
    • Hot flashes (in 15.7 vs 9.6 percent)
    • Falls (in 13.7 vs 8.1 percent)
    • Hypertension (in 12.2 vs 5.1 percent)
    • Dizziness (in 12.2 vs 7.1 percent)
    • Decreased appetite (in 11.7 vs 8.6 percent)

The authors conclude that enzalutamide demonstrated significantly superior outcomes to bicalutamide in these men with M0 and M1 CRPC and that “The safety profile of ENZA was consistent with that seen in previous studies of men with mCRPC.”

Perhaps not surprisingly, enzalutamide has a somewhat higher level of side effects than bicalutamide in these men. This would be consistent with its greater effectiveness as an anti-androgen and its greater ability to lower serum testosterone levels for longer periods of time.

One Response

  1. This research is encouraging but also what we expected, as Sitemaster has noted in mentioning the previous TERRAIN trial. We have known for a long time that enzalutamide was far better at binding to androgen receptor than bicalutamide, making it much better at blocking fueling of prostate cancer cells. A major knock on bicalutamide over the years is that it is not that impressive at doing its main job, which is binding to androgen receptor.

    However, as a now savvy veteran of intermittent ADT treatment that included bicalutamide for years, I am skeptical about some features of the study. First, the article above mentions that patients in the enzalutamide arm were on treatment substantially longer than patients in the bicalutamide arm, and we know that longer treatment with ADT typically leads to more favorable results. I’m curious whether the difference in length of treatment resulted from the protocol or because of an endpoint that was reached, such as progression. If per protocol, that was a confounding feature, as it would have given enzalutamide a substantial artificial advantage. The linked site does not clarify this issue.

    Second, I’m also curious about the dose of bicalutamide. The dose of enzalutamide used was 160 mg/day, which I assume is the dose approved by the FDA. The dose of bicalutamide was only 50 mg/day, and that leads me to suspect a potent, real confounding factor. That’s because the dose for men with metastatic disease prescribed by the medical oncologists I consider experts and have followed since 2000 has always been 150 mg/day, which is 3 pills/day, with the 50 mg dose used for men without detectable metastases, like me. At least one expert uses an even higher dose of 200 or 250 mg/day, guided by the patient’s circumstances and diligent monitoring. Therefore, a dose of only 50 mg/day of bicalutamide seems simply inadequate for men with metatstatic disease, of whom there was a substantial proportion in each arm of the trial: not enough drug to adequately block the androgen receptor docking ports of the cancer cells.

    This trial was funded by the makers of enzalutamide (Xtandi), and I’m thinking they set up a trial, perhaps inadvertently (though pretty glaring) where Xtandi was bound to look good, kind of like a horse race where one horse has to bear a lot more weight. I hope I’m wrong and have overlooked or misinterpreted something. Any thoughts?

    While these are critical comments regarding Xtandi, my impression is that it is a wonderful addition to our arsenal against prostate cancer.

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