Differing chemotherapies and their effects in the treatment of mCRPC


The results of two recent, large clinical trials may have some impact on the clinical use of cabazitaxel (Jevtana) in the treatment of late-stage prostate cancer.

The PROSELICA trial was designed to see whether a slightly lower dose of cabazitaxel (at 20 mg/m2 every 3 weeks, C20) might be as effective as the standard, original approved dose of cabazitaxel (25 mg/m2 every 3 weeks, C25) but have a slightly lower risk for side effects in the treatment of men with metastatic, castration-resistant prostate cancer (mCRPC) who had already been treated in docetaxel (Taxotere).

What Eisenberger et al. have now reported is that:

  • 1,200 patients were randomly assigned to this trial.
    • 602 patients were treated with C25.
    • 598 patients were treated with C20.
  • Baseline characteristics for the 1,200 patients were similar in both arms.
  • Average (median) overall survival was
    • 14.5 months for the patients treated with C25.
    • 13.4 months for the patients treated with C20.
  • There were significant differences between the PSA responses to the two different dose levels.
    •  42.9 percent of patients on C25 met the PSA cutoff criteria for an effective response.
    • 29.5 percent of patients on C20 met the PSA cutoff criteria.
  • Average (median) time to PSA progression was
    • 6.4 months for the patients on C25
    • 5.7 months for the patients on C20
  • Health-related quality of life did not differ between cohorts.
  • Rates of Grade 3 or Grade 4 treatment-emergent adverse events were
    • 54.5 percent for the patients on C25
    • 39.7 percent for the patients on C20

Eisenberger et al. conclude that:

  • The “efficacy of cabazitaxel in postdocetaxel patients with mCRPC was confirmed.”
  • The non-inferiority end point was met.
  • Cabazitaxel at a dose of  20 mg/m2 maintained ≥ 50 percent of the overall survival benefit of cabazitaxel at a dose of  20 mg/m2 versus mitoxantrone in the original TROPIC trial.
  • Secondary efficacy end points favored a cabazitaxel dose of  25 mg/m2.
  • Fewer adverse events were observed with a cabazitaxel dose of  20 mg/m2.

In contrast, the FIRSTANA trial was designed to test the efficacy and safety of docetaxel (at a dose of 75 mg/m2 every 3 weeks) versus C25 and versus C20 in as first-line chemotherapy in chemotherapy-naive men with mCRPC. In other words this was a three-arm, head-to-head trial.

Oudard et al. have now reported that:

  • 1,168 patients were randomly assigned to this trial (roughly 390 to each arm of the trial).
  • Baseline characteristics for the patients in each of the three arms were similar.
  • Average (median) overall survival was
    • 24.3 months for the patients treated with D75
    • 25.2 months for the patients treated with  C25
    • 24.5 months for the patients treated with C20
  • Average (median) progression-free survival was
    • 5.3 months for the patients treated with D75
    • 5.1 months for the patients treated with C25
    • 4.4 months for the patients treated with C20
  • Rates of Grade 3 and Grade 4 treatment-emergent adverse events were
    • 46.0 percent for the patients treated with D75
    • 60.1 percent for the patients treated with C25
    • 41.2 percent for the patients treated with C20
  • Adverse effects such as peripheral neuropathy, peripheral edema, alopecia, and nail disorders were more frequent with D75.
  • Adverse effects such as febrile neutropenia, diarrhea, and hematuria were more frequent with C25.

Oudard et al. conclude that:

  • C20 and C25 were not superior to D75 in terms of effect on overall survival in patients with chemotherapy-naïve mCRPC.
  • Tumor response was numerically higher with C25 versus D75 in patients with chemotherapy-naïve mCRPC.
  • Pain-related progression-free survival was numerically improved with D75 versus C25.
  • Cabazitaxel and docetaxel demonstrated different toxicity profiles, with less overall toxicity with C20.

What’s the overall bottom-line from these two studies? Frankly it’s hard to tell.

All three forms of treatment seem to have similar levels of effectiveness when it comes to overall survival. Conversely, cabazitaxel at the experimental dose level of 20 mg/m2 every 3 weeks seems to come with the lowest risk for side effects. The decision about what type of chemotherapy to use in an individual patient at a specific place along the course of his disease may indeed come down to a discussion about risk and benefit between the individual patient and his doctors.

3 Responses

  1. (Mike, it looks like the latter two lines for the following should be for C25 and C20 vs D75)

    “Rates of Grade 3 and Grade 4 treatment-emergent adverse events were

    46.0 percent for the patients treated with D75
    60.1 percent for the patients treated with D75
    41.2 percent for the patients treated with D75”

  2. Thank you Jim. Duly corrected.

  3. Dr. Nicholas Vogelzang’s Comments on Cabazitaxel (Jevtana®) Versus Docetaxel

    The FIRSTANA study that compared cabazitaxel and docetaxel does not seem to indicate much of an advantage to either drug, to my layman’s (now savvy survivor) eyes. However, a patient going to the well-known prostate cancer medical oncologist Dr. Nick Vogelzang for one of these drugs will be getting cabazitaxel, according to his comments at the PCRI/Us Too 2016 Conference on Prostate Cancer in LA last September (with the next edition coming next week, again in LA). It is interesting to see how these issues play out in an actual practice.

    As many of us know, Dr. Vogelzang has been a prominent clinical trialist for prostate cancer treatments, as reflected in his very heavy record as an author of research papers. In 2016 he was the conference presenter for developments featuring hormone resistance and bone metastases, which of course often involves chemotherapy.

    In essence, he made this striking statement: “By the way, I’m no longer doing docetaxel. I’m doing cabazitaxel because it is better tolerated and you can get to 10 doses better.” (Disc 2: a bit after 1:13) (Quite a “by the way” statement!) He echoed that a number of times, such as when he answered a question from a patient complaining about peripheral neuropathy: “The drug that I go to for patients with neuropathy is Jevtana [cabazitaxel], a much better drug than docetaxel. And usually you can get insurance to cover it if you put in your note [to the insurer] that the patient has neuropathy. Jevtana does not generally cause neuropathy.” (Disc 4: 1:52:56-1:53:37) In response to a patient asking about the worth of adding chemotherapy to ADT and the ways to mitigate side effects, he said: “I think that Jevtana is a good start. It’s got less neuropathic toxicities than the other one [docetaxel].” (Disc 4: 1:54:01 – 1:54:25) He answered a similar question from a patient who had been on “chemo”, Lyrica, Xtandi and soon to take Provenge, whose question ended with the key line, “Will these make peripheral neuropathy worse?” Dr. Vogelzang replied “No. That’s why I’m getting away from Taxotere (docetaxel) and using Jevtana more and more. But there’s no good drug. Lyrica is the drug that’s theoretically going to work, but we need better drugs.” (Disc 4: 2:02:43 – 2:03:26)

    Cabazitaxel did not get much other attention at the conference, in contrast to a lot of mention of docetaxel, probably because cabazitaxel is newer and trials have not matured? My impression is that it hasn’t had much of a buzz generally compared to other new drugs. The only other time at the conference that comes to mind is when Dr. Charles “Snuffy” Myers addressed a fellow panelist’s question about the use of chemoyherapy in the context of a patient who had been on or was considering Zytiga or Xtandi. Dr. Myers mentioned that such use of chemotherapy with these other drugs had been a hot topic at the 2016 ASCO conference, “with [prominent prostate cancer trialists] Dr. Maha Hussain arguing for chemo and [Dr.] Howard Scher [saying] maybe Xtandi should be given a try. And actually Nick [Vogelzang] who is not here [meaning on the roundtable panel] splitting the difference.” (Disc 3: about 49:35 – 51:01) Based on Dr. Vogelzang’s other comments, that chemotherapy, for him, would have been cabazitaxel.

    While Dr. Vogelzang has been heavily involved in research on a number of prostate cancer drugs, a review of PubMed did not show that he was an author of trial reports involving cabazitaxel; I found only one review article involving cabazitaxel for which he was an author. Therefore, it seems he is basing his comments on what he is observing in his own practice.

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