ASCO 2015: First Effective Adjuvant Chemotherapy for High-Risk, Localized Prostate Cancer
“For the first time, improvement in overall survival was observed with tolerable adjuvant chemotherapy for localized, high-risk prostate cancer,” Howard Sandler, MD, Professor of Radiation Oncology at Cedars-Sinai Medical Center in Los Angeles, announced at a press briefing at the 2015 ASCO Annual Meeting in Chicago. In a phase III clinical trial, patients who received docetaxel chemotherapy along with standard hormone and radiation therapy had a 4-year overall survival rate of 93% compared with 89% in the standard therapy group.
“This study is the first indication that chemotherapy has a role in the adjuvant treatment of localized prostate cancer, and we also expect to see an even bigger survival advantage over time,” said Dr. Sandler, the study’s lead author. “This finding could improve outcomes for thousands of men. At the same time, chemotherapy carries a modest increase in side effects, so it is important that physicians discuss the balance of benefits and risks with their patients.” Dr. Sandler presented detailed results at an oral abstract session on genitourinary (prostate) cancer (Abstract LBA5002).
Subset of Very High-Risk Cancer
Locally advanced or high-risk localized prostate cancer has a relatively poor prognosis. Among the most common cancers—lung, breast, colorectal, and prostate—prostate cancer is the only disease without an established adjuvant chemotherapy regimen. The study tested the hypothesis that “chemotherapy using docetaxel, a chemotherapy known to be beneficial in metastatic, hormone-resistant cancer, would improve outcomes in nonmetastatic, hormone-sensitive prostate cancer,” Dr. Sandler explained.
The study, RTOG 0521, assessed 563 men with high-risk, locally advanced prostate cancer. “This is actually a subset of very high-risk prostate cancer patients,” Dr. Sandler noted. “The worst, most aggressive cancers would be the best candidates for this,” he said. “Intermediate- or low-risk subsets, I would not recommend that they receive chemotherapy.”
Patients were randomly assigned to treatment with standard therapy (androgen suppression for 2 years plus external radiation therapy for 8 weeks) or standard therapy followed by docetaxel. Docetaxel was given for 18 weeks, starting a month after radiation therapy.
Reduction in Early Deaths
The difference in the overall survival (the study’s primary endpoint) of 93% with docetaxel and 89% without was statistically significant, with a hazard ratio of 0.70 (P = .04). At a median follow-up of 5.5 years, 52 deaths occurred in the standard therapy group compared with 36 deaths in the docetaxel group.
“This is a study that looked at early death from prostate cancer. The follow-up time of 4 years is relatively short in the lifetime of a prostate cancer patient being treated with curative intent. So a reduction in these early deaths is quite significant,” noted ASCO expert Charles J. Ryan, MD. Dr. Ryan is Professor of Clinical Medicine and Urology and Leader of the Genitourinary Medical Oncology Program at the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco.
Reduced Risk of Relapse
Docetaxel reduced the risk of relapse; the 5-year disease-free survival rate was 66% in the standard therapy group vs 73% in the docetaxel group. There was also a reduction in the incidence of distant metastases.
“The potential role of docetaxel in hormone-sensitive prostate cancer is consistent with and supported by our data and other studies, such as STAMPEDE and CHAARTED,” Dr. Sandler noted.
“These results are clinically relevant and that they come from a federally funded trial is also incredibly important,” commented ASCO spokesperson and press briefing moderator Don S. Dizon, MD. “The implications are wide, especially for those diagnosed with high-risk, locally advanced prostate cancer.” Dr. Dizon is Clinical Co-Director of Gynecologic Oncology and Director of the Oncology Sexual Health Clinic at Massachusetts General Hospital, Boston.
Continued Follow-up for Long-Term Benefit
Patient follow-up will continue to determine the long-term benefit of adjuvant chemotherapy in this setting, and an analysis of quality-of-life data will be performed at a later time. Dr. Sandler noted that future studies will explore the impact of adjuvant therapies among men with high-risk, localized prostate cancer.
This study received funding from The National Institutes of Health, Sanofi, and AstraZeneca. Dr. Sandler reported consulting or advisory roles with Medivation/Astellas, AstraZenenca, Janssen Pharmaceuticals, Bayer, and Eviti; other relationship with Caribou Publishing; research funding from Myriad Genetics; consulting or advisory role and research funding from Sanofi.
For full disclosures of the study authors, view the study abstract at abstract.asco.org.
Watch The ASCO Post Evening News for an interview with Dr. Sandler recorded live at the 2015 ASCO Annual Meeting.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
