CHICAGO—Adding docetaxel-prednisone chemotherapy to standard androgen ablation and radiation therapy reduces the risk of death for men with high-risk, localized prostate cancer, according to data from the Phase III RTOG 0521 study.
As reported here at the American Society of Clinical Oncology Annual Meeting (Abstract LBA5002), the four-year overall survival rates after 5.5 years of follow-up were 89 percent in the standard-therapy group versus 93 percent in the group who received added docetaxel group. Similarly, five-year disease-free survival rates were 66 and 73 percent, respectively.
“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 the study's lead author, Howard Sandler, MD, Professor and Chair of Radiation Oncology and Cancer Therapeutics at Cedars-Sinai Medical Center in Los Angeles. “This finding could improve outcomes for thousands of men.”
He said he and his colleagues hypothesized that the addition of adjuvant docetaxel (at a dose of 75 mg/m2) and prednisone (10 mg) to 24 months of androgen suppression (LHRH agonist before radiotherapy, oral antiandrogens through the end of radiotherapy) and three-dimensional conformal radiotherapy/intensity-modulated radiation therapy (3DCRT/IMRT) would increase overall survival.
RTOG 0521 was designed to detect improvement in four-year overall survival in patients in any of three categories:
- Gleason score 7-8, any T-stage, and PSA greater than 20 ng/mL;
- Gleason score 8, stage T2 or higher, any PSA level; or
- Gleason score 9-10, any T-stage, and any PSA level.
All men enrolled had PSA levels of at least 150 mg/ml. In four years the trial enrolled 563 patients who were evaluable for response, at sites in the U.S., Canada, and Australia: 281 were randomly assigned to androgen suppression-radiotherapy and 282 to androgen suppression-radiotherapy-docetaxel. Median age was 66, median PSA was 15.1 ng/mL, 53 percent of the men had Gleason scores of 9 to 10, and 27 percent had clinical T3-4 tumors.
Sandler said the trial was designed with a short overall survival assessment period, and additional follow-up is warranted to determine the long-term benefit of chemotherapy added to the current standard of care of long-term androgen-suppression and radiotherapy.
The study was supported by grants from the National Cancer Institute and Sanofi, with additional support from AstraZeneca for patients participating in Australia.
Consistent withCHAARTED and STAMPEDE
“The potential role of docetaxel in hormone-sensitive prostate cancer is consistent with, and supported by our data and other studies, including CHAARTED (2014) and STAMPEDE (2015),” Sandler said.
Patient follow-up will continue to determine the long-term benefit of adjuvant chemotherapy in this setting, he said, and an analysis of quality-of-life data will be performed at a later time.
Disagreement from Ian Tannock
The Discussant for the presentation, Ian Tannock, MD, PhD, Emeritus Professor of Medical Oncology at Princess Margaret Cancer Centre and the University of Toronto, Canada, though, disagreed with the implied recommendation of RTOG 0521, that docetaxel should routinely be added to standard androgen ablation-radiotherapy treatment.
“Given that RTOG 0521 reported a difference in overall survival of 93 percent versus 89 percent, using one-sided statistics, is this sufficient evidence to recommend docetaxel plus androgen-deprivation therapy after radiotherapy for men with M0 disease?” he asked rhetorically during his talk. It is expected that adding one active treatment—i.e., docetaxel in this case—to others, will lead to an improvement in disease-free survival.
“But disease-free survival improvement does not lead inevitably to improved overall survival.
“Men who don't receive docetaxel might live longer after disease progression. And if you look at the breast cancer literature there are many examples where adjuvant trials lead to disease-free survival but you don't get an improvement in overall survival. And in my view, for men with localized M0 disease if there is no effect on overall survival, then chemo delay is toxicity delay, and is the preferred strategy.
“Here is my recommendation: Men with localized M0 prostate cancer who receive local treatment with radiotherapy should not, in 2015, be routinely offered docetaxel in addition to androgen-deprivation therapy.”
Still, he said that this opinion might well change with longer follow-up on all three major trials: RTOG 0521, STAMPEDE, and GETUG-12.