ORLANDO, FL—As clinicians incorporate the use of docetaxel into the treatment algorithm for metastatic castration-resistant prostate cancer, the extended survival benefit experienced in the “real world” of actual practice appears to mimic the results observed in pivotal clinical trials, researchers reported here at the Genitourinary Cancers Symposium (Abstract 77).
“In this population-based analysis, the introduction of docetaxel as a standard of care was associated with a 2.8-month improvement in overall survival,” reported Robert R. Zielinski, MBBS, a prostate cancer research fellow at the British Columbia Cancer Agency in Vancouver.
The 21 percent hazard ratio reduction seen in his study of metastatic prostate cancer in British Columbia virtually matched the 21 percent reduction in the TAX-327 study by Ian Tannock et al that established docetaxel as a treatment for metastatic prostate cancer (NEJM 2004; 35:1502-1512).
Zielinksi reported a 6.8 percent absolute improvement in the number of men alive at two years with docetaxel treatment, which translated to a 43 percent relative improvement in men alive after two years.
The researchers scrutinized the British Columbia database to establish two cohorts of patients receiving palliative radiotherapy for the treatment of metastatic castration-resistant prostate cancer. One group were men treated prior to TAX-327, and the second received treatment after the report was published. The goal was to determine if the impact in the clinic matched the outcomes in the clinical trials.
The results showed exactly that: “This study demonstrates the generalizability of the TAX-327 study results to the population at large,” Zielinski reported in his poster presentation. He noted that the improvement in survival in the population occurred despite that fact that fewer than half of the patients eligible for docetaxel therapy in the post-TAX-327 era were treated with docetaxel.
“The pivotal TAX-327 study reported an updated hazard reduction for death of 0.79 for docetaxel versus mitoxantrone,” the researchers reported, noting that despite this benefit, the rates of utilization for docetaxel chemotherapy in metastatic castration-resistant prostate cancer patients remain about 30 percent internationally.
“Even with this selective use, we sought to determine whether the introduction of docetaxel has improved overall survival at a population level and whether docetaxel is an independent factor predicting improved overall survival.”
The study established that treatment with docetaxel, after multivariate analysis, was independently associated with a 35 percent reduction in the risk of death.
The researchers reviewed the medical records of men with castration-resistant prostate cancer who received palliative radiotherapy during the period of 1998 to 2001, and a second group of patients who received palliative radiotherapy from 2006 to 2009. The cohorts reflected the eras prior to and following the introduction of docetaxel as standard therapy.
The practice of palliative radiotherapy in British Columbia has remained stable across the two eras, Zielinski said, reporting that the rates of radiotherapy within three years of death were 43 and 42 percent in 1998-2001 and 2010. Ten percent of each cohort were randomly selected in an attempt to identify potential confounding factors across the two eras.
The median age of the 919 patients in the 1998-2001 cohort was 76; that for the 957 patients in the 2006-2009 era was 77. The time from diagnosis to radiotherapy to bone metastases was 3.9 years in the 1998-2001 cohort and 3.1 years in the 2006-2009 cohort.
In the 1998-2001 period, seven percent of the men received docetaxel; by 2006-2009, that had increased to 37 percent. About 30 percent of the 1998-2001 cohort had metastatic disease at diagnosis compared with 33 percent of those diagnosed during 2006-2009.
In terms of the characteristics of the 10 percent of patients randomly selected, 61 percent of the 1998-2001 cohort of 93 men had a Gleason score of 8 or greater, as did 68 percent of the 94 men in the 2006-2009 group.
The median survival after the first palliative radiotherapy to the bone was 10.3 months in the 2006-2009 group compared with 7.5 months in the 1998-2001 cohort, representing a 21 percent reduction in the relative risk of death.
Despite Evolving Therapeutic Landscape with New Agents…
“Even as the therapeutic landscape for castration-resistant prostate cancer evolves with new agents, these data support the continued use of docetaxel in appropriately selected patients,” Zielinski said.
Asked for his opinion for this article, Ian Thompson, MD, Professor and Chair of Urology at the University of Texas Health Science Center at San Antonio, called the study reassuring. “These are interesting observations and they fit with what the randomized trials have shown. When you look at what happens in the real world you are never really sure why one person got a drug and another person didn't.
“But in the trials that established docetaxel, the eligibility criteria were quite similar to the patients you see in the clinic. So it's not surprising that the real world results were similar to the trials.”
© 2013 Lippincott Williams & Wilkins, Inc.