Avanafil in treatment of post-surgical ED for men with localized prostate cancer

Data published on line in the Journal of Urology last December suggest that the new PDE5 inhibitor known as avanafil or Stendra® is supposedly effective in combating erectile dysfunction (ED) in just over one-third of men with ED at 6 months after bilateral, nerve-sparing radical prostatectomy.

The study by Mulhall et al. offers data from a three-arm, randomized, placebo-controlled clinical trial, conducted in 298 patients who were enrolled at 53 clinical trial sites in the USA. The trial was designed to assess the effectiveness and safety of avanafil in men with moderate to severe ED at 6 or more months after bilateral, nerve-sparing radical prostatectomny, and the patients were not permitted to use any other form of penile rehabilitation technique or device during the course of the trial. In addition, patients had to have had a pathological stage of ≤ T2bN0M0 at prostatectomy and a Gleason score of ≤ 4 + 3 = 7.

After a 4-week, non-treatment “run-in” period, during which the patients were asked to make at least four attempts to have sexual intercourse, eligible patients with a ≥ 50 percent failure rate  were randomized to treatment with avanafil at doses of 100 mg or 200 mg or a placebo. The study drug was to be taken about 30 minutes prior to initiation of sexual activity and up to two doses could be taken within a 24-hour period (if taken at least 12 hours apart). The study was conducted over a period of 12 weeks. Primary study endpoints included successful vaginal insertion (SEP2), successful intercourse (SEP3) and change in score on the erectile function domain of the IIEF-EF questionnaire.

Here are the core study results:

  • 71.5 percent of the 298 patients enrolled had severe ED at baseline (with a mean IIEF-EF score of 9.2).
  • The mean success rate for successful intercourse during the non-treatment, run-in period was < 5 percent.
  • Just 16.1 percent of patients were ≥ 65 years of age
  • 80.5 percent of the patients had had a robot-assisted radical prostatectomy.
  • The three treatment groups were largely comparable with respect to medical history; however, more patients in the avanafil 100 mg group had a history of hypertension.
  • 252/298 patients initially enrolled (84.6 percent) completed the study.
  • 46 patients did not complete the study, including
    • 8.1 percent of patients in the avanafil 200 mg group
    • 14.1 percent of patients in the avanafil 100 mg group
    • 24.0 percent of patients in the placebo group
  • After 12 weeks on treatment, the trial showed
    • Significantly greater increases in SEP2 and SEP3 and change in mean IIEF-EF domain score with avanafil 100 mg and 200 mg, compared with placebo (p <0.01).
    • 28/77 sexual attempts (SEP3), i.e., 36.4 percent, were successful at ≤ 15 minutes after dosing with avanafil (at either dose level), as compared to only 2/44 sexual attempts (4.5 percent) after treatment with the placebo.
  • Avanafil was generally well tolerated.
    • No serious advese events were reported.
    • < 2 percent of patients discontinued from the study due to an adverse event.

Mulhall et al. conclude that avanafil was “effective and well tolerated in improving EF post-prostatectomy” at both 100 and 200 mg. They further comment that the drug appeared to have “a rapid onset of action and sustained duration of effect.”

7 Responses

  1. Any idea how this compares with results from the other PDE5s?

  2. Boy howdy, that’s a study about Avanafil that tells one everything one needs to know about robot-assisted radical prostatectomy and the ability of “young” men to heal from it.

    And, while I certainly understand the methodology of random assignment, I wonder how many of these 300 men fully understood they were giving precious time that cannot be regained to start a full regimen of rehabilitation? I’ve got to wonder if they realized they were greatly reducing the likelihood of full functioning for the rest of their life for a pharmaceutical company and journal article publication.

    Happy Valentine’s Day!

  3. Dear Tracy:

    I should point out that there is absolutely no suggestion in the trial protocol that the men enrolled in this trial could not previously have tried other forms of PDE5 inhibitor, and the trial protocol clearly states that participants can be using other forms of stimulant than PDE5 inhibitors during the trial.

    The protocol does state that it excludes men who have any allergy or hypersensitivity to PDE5 inhibitors or any of the components of these drug products and men with a history of dose-limiting adverse events during prior treatment with a PDE5 inhibitor or who have discontinued use of a PDE5 inhibitor due to lack of efficacy at the highest tolerated dose.

    In other words, you can’t make the assumption that these men hadn’t previously been using a different PDE5 inhibitor as part of a penile rehabilitation regimen, and the full text of the paper (which I have not seen) probably includes detailed data on this matter.

  4. Jonathon:

    That would require a direct comparative trial of avanafil against competitive PDE5 inhibitors like sildenafil or tadalafil. I do not believe any such trials have been conducted.

  5. Tracy:

    One other comment … Respectfully, this trial doesn’t tell us anything at all about the risk for severe ED after either RALP or any other form of RP. All that it tells us is that of the 298 men who enrolled in this trial, 71.5% had severe ED. But the trial was designed to enroll such men, so men who did not have ED after a RALP or other RP wouldn’t have tried to enroll in it!

    And this does not mean that I am trying to play down the risk for ED after surgery for prostate cancer, which is quite certainly high. I am merely pointing out that you cannot draw any meaningful conclusion from these data about that risk.

  6. “and the patients were not permitted to use any other form of penile rehabilitation technique or device during the course of the trial.”

  7. Oooops … Mea culpa … Missed the “not.”

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