Christopher Sweeney, MBBS
Administering chemotherapy concurrently with androgen deprivation therapy (ADT), rather than saving cytotoxic treatment until after progression, improves overall survival for men with hormone-sensitive metastatic prostate cancer, a study has demonstrated.
Patients who concurrently received ADT and the chemotherapy drug docetaxel had a 3-year survival rate of 69%, as compared with a 3-year survival rate of 52.5% for men in the same population who received ADT alone, investigators found in study E3805.
“The results of this study are practice-changing,” said lead investigator Christopher Sweeney, MBBS, clinical director of Genitourinary Oncology at the Dana-Farber Cancer Institute in Boston. “We have strong scientific evidence that patients with the most advanced metastatic prostate cancer benefit from the early addition of docetaxel to ADT and not waiting until the cancer has progressed on hormonal therapy. The findings of this study are important both for improving the clinical care we deliver now and in designing new clinical trials as we strive to further improve the lives of men with metastatic prostate cancer.”
“Additionally, these findings are an example of how combining two approved and available treatments can produce a significant improvement in clinical outcome,” said Jeff Abrams, MD, clinical director of the Division of Cancer Treatment and Diagnosis at the National Cancer Institute (NCI), which sponsored the study.
The positive results were released prior to the study’s close after a planned interim analysis, at the recommendation of the independent Data and Safety Monitoring Committee overseeing the trial, according to a written statement about the findings released by the National Institutes of Health, which includes the NCI.
In the study of 790 men with metastatic prostate cancer, patients received either ADT alone or ADT with docetaxel every 3 weeks for a total of 18 weeks. In addition to recording an overall survival benefit, investigators observed that men who had a high extent of metastatic disease at the start of treatment were the most likely to benefit from the drug pairing, with a 3-year survival rate of 63.4%. Men with a high level of metastatic disease who took ADT alone had a 3-year survival rate of 43.9 %, according to the statement.
The researchers stratified the subgroups by determining at the study’s outset whose disease had spread to major organs such as the liver and/ or resulted in four or more bone lesions. Further follow-up will be performed on trial participants with less extensive metastatic disease, in order to determine their response to the treatment combination, the statement said.
In men with metastatic prostate cancer, the typical treatment sequence is initial ADT; then, after progression, newer hormonal therapies such as abiraterone and enzalutamide; and finally, after further progression, chemotherapy, Sweeney told Oncology & Biotech News
In the past, physicians have paired chemotherapy with ADT before a patient developed castration-resistant prostate cancer only on an “ad hoc basis,” and it was considered “off protocol,” Sweeney said. Based on the data generated in study E3805, physicians now have a rationale for using the pairing more regularly, Sweeney said. The NCI statement cautioned, however, that doctors should restrict their use of this combination to patients with high-extent metastatic prostate cancer who are candidates for treatment with docetaxel, since the chemotherapy is associated with some toxicities.
Since docetaxel has already been approved by the FDA for the treatment of late-stage prostate cancer, and ADT is also an approved therapy, physicians don’t have to wait for government approval before using the new strategy, Sweeney noted. “In the US, seeing as it is approved, I think the only barrier will be insurance approval,” he said.
Sweeney said that he and the study’s other investigators will present their data at scientific meetings and publish it in peer-reviewed journals this year in order to inform the oncology community, encourage their use of the new strategy, and seek the inclusion of the drug pairing in treatment guidelines for this patient population.
National Institutes of Health. NIH-funded study shows increased survival in men with metastatic prostate cancer who receive chemotherapy when starting hormone therapy. NIH website. http://1.usa.gov/1cP1Eac. Published December 5, 2013. Updated December 6, 2013. Accessed January 7, 2013.