More data to come at ASCO in June

We commented earlier today on the positive data about tasquinimod that will be presented at the ASCO annual meeting. Negative data will unfortunately be presented on other drugs, but not everything is doom and gloom.

Back in March, Roche had announced that the Phase III clinical trial of docetaxel and prednisone with and without bevacizumab (Avastin) in patients with metastatic castration-resistant prostate cancer (mCRPC) had failed to meet the primary endpoint. In other words, the addition of bevacizumab to docetaxel and prednisone did not increase overall patient survival compared to docetaxel + prednisone. These data are going to be presented at ASCO, but the abstract has been withheld from publication until Sunday, June 6, so we are going to have to wait to see the actual results of this trial.

It is worth noting that a small, German, Phase II trial compared a second round of treatment with docetaxel + prednisone to treatment with docetaxel + prednisone + bevacizumab in mCRPC patients who were in relapse after a first round of treatment with docetaxel + prednisone. In this study, which involved just 59 patients, Heidenreich et al. demonstrated a 4.2-month increase in overall survival for the patients who received bevacizumab. Whether this will be enough to justify the regular use of docetaxel + prednisone + bevacizumab as second-line chemotherapy for mCRPC remains to be seen. This survival benefit is longer than the 2.4 month benefit previously reported for cabazitaxel (see this ASCO abstract for the final results of the TROPIC trial), but would need to be replicated in a randomized, double-blind phase III trial to be fully confirmed. Such a trial seems unlikely after the failure of the large Phase III trial mentioned above.

Another trial which appears to have been less successful than hoped is the Phase II clinical trial of Eisai’s investigational drug eribulin mesylate, again in men with mCRPC. This was a multicenter trial conducted by the Eastern Cooperative Oncology Group (ECOG). Patients with progressive mCRPC were treated with intravenous eribulin over 5 minutes on Days 1 and 8 of a 21-day cycle. It was a non-comparative study in which patients were stratified into three groups: chemo-naïve patients, prior-taxane-only patients, and patients treated with two prior chemotherapy regimens.

The results of this study showed the following:

  • 119 patients received treatment in this trial, and 116 were eligible for the evaluation for the primary response.
  • Median patient age was 70 years (range 45 to 88 years).
  • Only one patient remained on treatment at the time of the analysis.
  • 82/115 eligible patients had discontinued treatment due to disease progression.
  • 65/116 eligible patients had required eribulin dose modifications (planned and unplanned).
  • Only 24 percent of patients in the chemo-naïve group showed a 50 percent reduction in their PSA level (as compared to the anticipated 40 percent of patients).

The authors conclude that while eribulin demonstrated activity as a single agent in patients with taxane-naïve mCRPC, the overall response rate did not meet the anticipated levels of activity. They also noted that a clinically significant degree of myelosuppression was observed in all three patient groups. It appears that, at least at this time, there is no further intent to study the activity of eribulin in patients with CRPC.

The ASCENT2 trial is a third study which failed to show an overall survival benefit for the active drug combination (docetaxel + prednisone + high-dose calcitriol) compared to the standard of care (docetaxel + prednisone + placebo). As was the case for the bevacizumab trial, the negative result of this trial was announced some time ago (actually in November 2007) by Novacea, but the final results are being presented at the ASCO meeting for the first time.

The bottom line to data from ASCO on new treatments for men with CRPC seems to be that:

  • We are still waiting for Phase III data on abiraterone acetate in patients who have relapsed after docetaxel + prednisone.
  • We know that carbazitaxel holds considerable promise, and we can hope it will be approved some time early next year.
  • Tasquinimod has also shown some interesting data.
  • A combination of bevacizumab, docetaxel, and predisone cannot be ruled out as a “last line of defense.”

There had been some hope that the Phase III data from the major abiraterone trial might be available in time for this ASCO meeting. We are now going to have to wait and see whether these data will be announced at or before the Gentiourinary Cancers meeting in early 2011.

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