Patient preference and type of chemotherapy for mCRPC

In another presentation from the ESMO meeting in  Madrid, Spain, Fizazi et al. presented data from the randomized CABA-DOC trial  exploring patients’ preferences for either docetaxel or cabazitaxel as a first-line form of chemotherapy.

Docetaxel and cabzitaxel are the two forms of taxane chemotherapy that are approved for the treatment of metastatic, castration-resistant prostate cancer. Historically, docetaxel (Taxotere) has long been used first with cabazitaxel (Jevtana) as the second-line chemotherapeutic agent … but might the reverse order be better? Although data have suggested similar levels of efficacy of these two taxanes when they are used as first-line forms of chemotherapy, it is recognized that the two drugs do have different safety profiles.

Once again, this commentary is based on a report by Dr. Zachary Klaassen on the UroToday web site.

The CABA-DOC study was designed as a randomized, Phase III, cross-over trial, conducted at 17 different centers. Patients with well-documented mCRPC were randomized on a 1:1 basis to be treated with

  • Either docetaxel (75 mg/m2/q3w ×4) followed by cabazitaxel (25 mg/m2/q3w ×4)
  • Or cabazitaxel (25 mg/m2/q3w ×4) followed by docetaxel (75 mg/m2/q3w ×4)

Randomization was stratified based on prior abiraterone or enzalutamide therapy. The primary endpoint was patient preference between the two taxanes, assessed in patients who had received at least one cycle of each taxane and who had not experienced a progression after the first taxane.

Here are the study findings:

  • 195 patients were recruited between June 2014 and October 2016.
  • The patients’ average (median) age was 70 years.
  • The patients’ average (median) PSA level was 49 ng/ml at randomization.
  • Patients received 3.8 ± 0.7 and 3.2 ± 1.5 cycles of chemotherapy during the first and the second periods, respectively.
  • 150/195 patients were actually eligible for evaluation.
  • Among these 150 patients
    •  66 (44 percent) preferred cabazitaxel as first-line therapy.
    • 40 (27 percent) preferred docetaxel as first-line therapy.
    • 44 (29 percent) expressed no preference between the two taxanes.
    • 66 (44 percent) preferred the first taxane they were treated with.
    • 40 (27 percent) preferred the second taxane they were treated with.
    • 44 (29 percent) had no preference based on order of treatment.
  • These preferences were statistically significant (p = 0.009).
  • The two primary reasons given by patients for expressing a preference were less fatigue and improved quality of life.
  • 3/195 patients (1.5 percent) experienced toxicity-related deaths).

At the present time, given that docetaxel is generically available whereas cabazitaxel (Jevtana) is a still a branded product, cost may be a key factor in being able to access cabazitaxel as a first-line taxane in the treatment of mCRPC compared to docetaxel. On the other hand, there does seems to have been a clear difference in the degree to which patients preferred cabazitaxel as opposed to docetaxel: 25 percent more patients chose cabazitaxel as opposed to docetaxel among those who actually felt able to make a choice.

Whether this difference is sufficiently meaningful to overcome the differences in cost of treatment is still being investigated.

2 Responses

  1. This is a surprise for me. We have a Danish study in which a quarter of the patients given cabazitaxel were admitted to hospital due to toxicity and a quarter of the patients stopped further treatment with cabazitaxel. I am not aware of similar toxicity with docetaxel.

    In the recent APCCC 2017 consensus, leading experts recommend giving cabazitaxel at a dose of 20 mg/m2 body surface with growth factor support to reduce myelosuppression after cabazitaxel. There has been a trial in which overall survival for the low-dose cabazitaxel and the high-dose cabazitaxel were nearly identical. So the choice of the medical oncologists at the APCCC should be taken into account for all who sadly have a situation where it is a relevant problem.

  2. I was delighted to read about Dr. Miguel Martin receiving his ESMO award in Madrid. He was one of the first (if not the first) to recognise/acknowledge permanent alopecia caused by Taxotere/docetaxel.

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