Data from the TRAPEZE trial are “unsurprising” in mCRPC


The only late-breaking, prostate cancer-specific paper to be presented at the annual meeting of the American Society of Clinical Oncology (ASCO) this year was from the TRAPEZE study carried out in the UK.

The results of this this study were reported by James et al. this morning, and can reasonably be described as “unsurprising.”

TRAPEZE was initially designed as a four-arm study in which men with metastatic, castration-resistant prostate cancer (mCRPC) were randomized to one of the following four different forms of therapy:

  • Chemotherapy with six cycles of docetaxel + prednisolone (trial arm A)
  • Chemotherapy with six cycles of docetaxel + prednisoolne and zoledronic acid (trial arm B)
  • Chemotherapy with six cycles of docetaxel + prednisolone and a single dose of strontium-89 (trial arm C)
  • Chemotherapy with six cycles of docetaxel + prednisolone and both other agents (trial arm D)

In assessing the results of this trial, it is important to remember that zoledronic acid (alson know as zoledronate or Zometa) was approved because of its ability to reduce skeletal-related events (SREs) in men being treated for metastatic prostate with androgen deprivation therapy. Similarly, strontium-89 (an injectable form of radiation therapy) was approved as a palliative agent to control pain from metastases and to reduce the need for subsequent bone treatments.

It appears that enrollment of patients to Arm 4 of this trial may have been prematurely terminated. (This is not clear from the abstract and unfortunately your correspondent missed the first two slides of Dr. James’ presentation.)

Here are the results presented by Dr. James this morning:

  • TRAPEZE enrolled and randomized a total of 757 patients.
    • The median age of these patients at randomization was 68.7 years.
    • The median PSA of the patients was 144 ng/ml.
    • 40 percent of these men had an ECOG performance score of 0.
    • 52 percent of them had an ECOG performance score of 1.
    • 8 percent of them had an ECOG performance score of 2.
    • 45 percent of the patients had previously received radiation therapy.
  • Compared to treatment with Arm 1
    • Clinical progression-free survival was not apparent among patients in Arm 2 (p = 0.46).
    • A small but statistically significant clinical progression-free survival benefit — of about a month — was apparent among patients in Arm 3 (hazard ratio [HR] = 0.845; p = 0.036).
    • Patients in Arm 2 did demonstrate a significant improvement– of about 5 months — in time to occurrence of SREs (HR = 0.76; p = 0.008).
    • There was no evidence of any improvement in overall survival of patients in either Arm 2 or Arm 3.
    • No data were presented for patients in Arm 4.

James et al. conclude that:

  • Six cycles of docetaxel + predisolone + a single injection of strontium-89 did (very slightly) improve clinical progression-free survival (but not overall survival) compared to just docetaxel + prednisolone.
  • Six cycles of docetaxel + predisolone + zoledronic acid had no effect on either clinical progression-free survival or overall survival compared to docetaxel + prednisolone alone.
  • The addition of zoledronic acid to therapy with docetaxel + prednisone did significantly improve median time to initiation of skeletal-related events, but that this happened mostly after progression on chemotherapy, suggesting a role for zoledronic acid as post-chemotherapy maintenance treatment.

Commenting on this study in his session review, Oliver Sartor, MD, seemed to agree with these conclusions, noting that the very small effect on strontium-89 on progression-free survival was probably not of any practical significance but that the effect of zoledronic acid on delay of onset of skeletal-related effects almost certainly was clinically meaningful.

2 Responses

  1. Considering that in head-to-head trials Xgeva/denosumab delayed SREs (skeletal-related events) with clinically meaningful improvement of 27.6 months vs Zometa/zoledronate 19.4 months, it would appear that prescribing docetaxel/Taxotere accompanied by prednisone and denosumab/Xgeva would be even more promising.

  2. For anyone interested, I’ve posted the slides on my Twitter feed (@Prof_Nick_James) , as well as pictures of Oliver Sartor’s discussion. Not sure this is a fair assessment of the results. The key point is that we collected clinical SRE data, not radiological ones as in the zoledronic acid (ZA) licencing trial. Hence the big reduction seen is the first demonstration of unequivocal clinical gain from ZA, an agent the National Health Service (in the UK) does not support for prostate cancer. The trial also shows that docetaxel prevents about 50% of patients from having clinical SREs or symptomatic skeletal events (SSEs) as they are more accurately described. The final component, strontium-89, prolonged disease-free survival by about a month.

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