Two abstracts presented during the Genitourinary (Prostate) Cancer Oral Abstract Session on Sunday, May 31, showed significantly improved overall survival (OS) when docetaxel chemotherapy was added to standard hormone therapy in patients with advanced, hormone-naive prostate cancer (Abstract 5001) and hormone therapy plus radiation therapy in men with high-risk localized prostate cancer (Abstract LBA5002).
Dr. Howard M. Sandler
Nicholas D. James, MD, PhD, of the University of Warwick and Queen Elizabeth Hospital Birmingham, United Kingdom, presented the first OS results from the randomized, controlled STAMPEDE trial, a multistage, multi-arm assessment of therapies for men with advanced, hormone-naive prostate cancer.
The trial was designed to continuously adapt the standard of care (SOC) aspect of the trial as new treatment options emerge. Dr. James presented results of four of the trial’s arms, which randomly assigned 2,962 men at a 2:1:1:1 ratio to SOC alone (at least 3 years of androgen-deprivation therapy with radiation when needed), SOC plus six cycles of docetaxel, SOC with zoledronic acid for 2 years, or SOC with docetaxel and zoledronic acid.
Sixty-one percent of the men had metastatic disease, and the rest had locally advanced, non-metastatic prostate cancer. Patients were followed for a median of 42 months.
There were 165 deaths in the SOC plus docetaxel arm compared with 405 in the SOC alone arm. Men assigned to docetaxel had a significantly improved median OS of 77 months compared with 67 months for men in the SOC arm (hazard ratio [HR] 0.76, 95% CI [0.63, 0.91]; p = 0.003). In addition, docetaxel improved failure-free survival compared with SOC alone (37 vs. 21 months; HR 0.62, 95% CI [0.54, 0.71]; p < 0.0000000001).
“Docetaxel should be considered for routine practice in suitable men with newly diagnosed metastatic disease,” Dr. James said. “It should be considered for selected men with high-risk, non-metastatic disease in view of substantial prolongation of failure-free survival.”
When the researchers looked at just those patients with metastatic disease, they found a 22-month improvement in OS compared with SOC alone (65 vs. 43 months; HR 0.73, 95% CI [0.59, 0.89]; p = 0.002).
The addition of zoledronic acid to SOC did not improve failure-free survival (HR 0.93; 95% CI [0.82, 1.05]; p = 0.26) and OS (HR 0.93, 95% CI [0.79, 1.11]; p = 0.44) compared with SOC alone. The combination of zoledronic acid plus docetaxel did result in an improvement in OS compared with SOC alone (72 vs. 67 months; HR 0.81, 95% CI [0.68, 0.97]; p = 0.02), but the regimen was not more effective than the addition of docetaxel alone.
Thirty-one percent of patients in the SOC and SOC plus zoledronic acid arms experienced grades 3-5 adverse events, with the rate of adverse events increasing to slightly more than 50% in the two chemotherapy arms.
Howard M. Sandler, MD, of Cedars-Sinai Medical Center, presented the results of the phase III RTOG 0521 trial, a federally funded trial that compared outcomes in 562 men with high-risk, localized prostate cancer treated with androgen suppression and radiation therapy with or without the addition of adjuvant chemotherapy with docetaxel and prednisone.
The men were randomly assigned to standard therapy alone, defined as radiation therapy plus 2 years of androgen suppression, or standard therapy followed by six 21-day cycles of docetaxel/prednisone starting 4 weeks after radiation.
After a median of 6 years follow-up, there were 36 deaths in the chemotherapy arm compared with 52 in the standard therapy arm. The 4-year OS was 93% for the docetaxel/prednisone arm compared with 89% in the standard therapy arm (HR 0.70, 95% CI [0.51, 0.98]; p = 0.04).
Patients assigned to the docetaxel/prednisone arm had an improved 5-year disease-free survival rate of 73% compared with 66% for patients assigned standard therapy alone. The addition of docetaxel/prednisone resulted in a reduction in deaths from prostate cancer (23 vs. 16) and deaths due to other or unknown causes (36 vs. 27).
“For the first time, improvements in overall survival were observed with tolerable adjuvant chemotherapy for high-risk, localized, hormone-sensitive prostate cancer,” Dr. Sandler said. “Additionally, the cumulative incidence of distant metastasis was reduced.”
The discussant of these two abstracts, Ian Tannock, MD, PhD, of Princess Margaret Cancer Centre, University of Toronto, Canada, viewed the STAMPEDE trial as a success and recommended that men with high-risk metastatic prostate cancer—especially those presenting with metastases at or soon after diagnosis who are eligible to receive chemotherapy—should be offered six cycles of docetaxel in addition to androgen deprivation therapy.
However, Dr. Tannock also emphasized that “these trials do not represent men that we more commonly see with slowly progressing disease who develop metastases several years after diagnosis, whether they get local treatment or not.”
In his review of RTOG 0521, Dr. Tannock questioned the trial’s use of one-sided statistics, and pointed out that the difference in OS was not significant if conventional statistics were employed, resulting in a p value of 0.08. In addition, the trial did not meet its own prespecified criteria for a positive trial, which was a 4-year OS rate between 86%-93% with an HR of 0.49—an HR that he said would have been very unlikely to ever be achieved.
Based on this, Dr. Tannock said he would be, but was not yet, willing to recommend docetaxel in addition to androgen deprivation therapy for men with localized nonmetastatic prostate cancer who are scheduled to receive radiation therapy; however, he noted that his opinion might change with longer follow-up of this and other similar studies.
Watch the session: Visit the ASCO Virtual Meeting website.