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Lenalidomide combination fails to improve survival in castration-resistant prostate cancer
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The addition of lenalidomide to docetaxel and prednisone was associated with a significantly greater mortality rate in patients with metastatic castration-resistant prostate cancer, according to phase 3 study results.
Daniel P. Petrylak, MD, professor of oncology and urology at Yale School of Medicine and a HemOnc Today Editorial Board member, and colleagues evaluated data from 1,046 chemotherapy-naive patients with metastatic castration-resistant prostate cancer.
Daniel P. Petrylak
Researchers randomly assigned 525 patients to receive docetaxel and prednisone plus lenalidomide (Revlimid, Celgene). The other 521 patients received docetaxel and prednisone plus placebo.
After a median follow-up of 8 months, 221 patients had died (lenalidomide arm, n = 129; placebo arm, n = 92). The number of deaths that occurred during treatment or within 28 days of receiving the final dose was similar in both groups (lenalidomide, n = 18; placebo, n = 13).
Death more than 28 days after receipt of the final dose — primarily due to disease progression — occurred more frequently in the lenalidomide arm (21% vs. 15%).
Median OS was significantly shorter in the lenalidomide arm (17.7 months vs. not yet reached; HR = 1.53; 95% CI, 1.17-2).
Grade 3 or worse adverse events occurred in 73% of patients assigned lenalidomide and 58% of patients assigned placebo. More patients assigned lenalidomide experienced grade 3 to grade 4 neutropenia (22% vs. 16%), febrile neutropenia (12% vs. 4%), diarrhea (7% vs. 2%) and pneumonia (5% vs. 1%).
The trial was closed prematurely due to futility.
“The lack of efficacy of lenalidomide might result from several factors, including drug administration, toxicity and mechanisms of resistance to anti-angiogenic agents,” Petrylak and colleagues wrote. “Addition of lenalidomide to a standard regimen of docetaxel plus prednisone did not provide any benefit in terms of OS in chemotherapy-naive patients with metastatic castration-resistant prostate cancer; in fact, OS was significantly better in the placebo group than in the lenalidomide group. Further studies of this combination are not warranted.”
In an accompanying editorial, Francesco Boccardo, MD, of the department of medicine at the University of Genoa Medical School and of the academic unit of medical oncology at San Martino-National Cancer Research Institute, described the study results as an “expected failure.”
“Different messages or lessons can be drawn from this study,” Boccardo wrote. “The investigators rightly conclude that further research into this combination is not warranted, and recognize that more stringent methodology should be required to proceed to larger studies, including early-phase data to ensure target inhibition to clinical effect, selection of appropriate endpoints for randomized phase 2 and phase 3 studies, and identification of rigorous stopping rules that would protect patients from undue exposure to toxicity and ineffective treatment. However, the true lesson of this study is that biomedical research cannot ignore the best interests of the patients, nor should the developmental pathways for drugs be rushed inappropriately.” –by Cameron Kelsall
Disclosure: The researchers report consultant/advisory roles or employment with, equity ownership in, and research funding or honoraria from Celgene, Sanofi Aventis, US Oncology Research and Veridex.
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