CELG: A Very Negative Revlimid Trial in Prostate Cancer Caused Outrage among Clinicians
• In a late-breaker presentation on Sunday, Celgene's Phase 3 trial of Revlimid in
combination with docetaxel and prednisone was presented. The trial showed a dramatic
detriment in patients who received Revlimid. The hazard ratio comparing the Revlimid arm
and the placebo arm was 1.53 (1.17, 2), meaning a prostate cancer patient who received
Revlimid had a 53% higher chance of dying compared to a patient who received placebo. The
PFS was similar between the 2 arms: 45-week Revlimid versus 46-week placebo. The
objective response numerically favored placebo: 22.1% Revlimd versus 24.3% placebo.
• The trial received a scathing review by the discussant following the data
presentation. He pointed out that this disastrous outcome could have been avoided, since
there were few early clinical trial data to support moving the drug into a large-scale
Phase 3 trial which involved over 1,000 patients, and there were earlier data pointing to
overlapping toxicity of the drugs in the regimen. Indeed, we couldn't recall ever seeing
a large-scale Phase 3 trial that resulted in a 53% increase in the risk of patients
dying. In most cases when a Phase 3 trial fails, there is still a trend towards the drug
having benefit, just not to the degree of statistical significance. At worst, the failed
trials result in a slight detriment in outcome, but never to this degree. Indeed, the
main point of Phase 1 and Phase 2 trials is to minimize avoidable risks in a large group
of trial participants in Phase 3. We think this trial will cause many institutional
review boards to think twice before approving a Celgene-sponsored Revlimid trial in solid
tumors. Additionally, almost all solid tumor therapies involve some cytotoxic agents
administered either concurrently or in tandem with the proposed use of Revlimid. The
overlapping toxicity of Revlimid with these agents should call into question Celgene's
strategy of expanding Revlimid usage beyond hematology and into solid tumors.
