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Results from the large STAMPEDE trial suggest that the combination of zoledronic acid and celecoxib along with standard of care could improve failure-free survival in prostate cancer patients starting hormone therapy whose disease has metastasized.
Results from the large STAMPEDE trial suggest that the combination of zoledronic acid and celecoxib along with standard of care could improve failure-free survival in prostate cancer patients starting hormone therapy, but only in those whose disease has metastasized. There was no significant effect in the overall study population. Results were presented at the 2016 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, held January 7–9 in San Francisco (abstract 162).
“The hypothesis we’re testing in STAMPEDE is if we add additional therapy at the time of diagnosis in men at risk of dying from prostate cancer and starting hormone therapy, we may well see a survival gain, and we may maximize that gain by starting these agents early,” said Nicholas D. James, BSc, MBBS, PhD, of the University of Warwick Queen Elizabeth Hospital in Birmingham, United Kingdom.
The trial had a number of treatment arms, results of several of which have been presented or published earlier. Previous work has suggested that inhibition of COX-2 with agents such as celecoxib could inhibit the growth and invasiveness of prostate cancer cells, and epidemiologic studies have suggested a protective effect against prostate cancer from nonsteroidal anti-inflammatory drugs.
In this presentation, James showed data comparing a standard of care group only (SOC; 622 patients), an SOC plus celecoxib group (312 patients), and an SOC plus celecoxib and zoledronic acid group (311 patients). After a median follow-up of 63 months, 36% of the full cohort had died from prostate cancer, 9% died of other causes, and 55% remained alive.
In the celecoxib group, the median failure-free survival was 22 months, compared with 19 months in the SOC only group. The 5-year failure-free survival rates were 29% and 26%, respectively, and the hazard ratio (HR) for failure-free survival with celecoxib was 0.88 (95% CI, 0.75–1.04; P = .122).
Similarly, the median overall survival was 69 months with celecoxib and 68 months with SOC, and the 5-year overall survival rate was 54% in both groups. The HR for overall survival was 1.00 (95% CI, 0.82–1.22; P = .986). There was a trend toward some benefit in only the metastatic patients, but this was still not significant.
In the combination celecoxib and zoledronic acid group, however, that benefit did reach significance. In only metastatic patients, the HR for failure-free survival was 0.77 (95% CI, 0.63–0.93; P = .008), and the HR for overall survival was 0.78 (95% CI, 0.62–0.99; P = .040).
In all patients, the combination therapy did not significantly improve failure-free survival, at 24 months vs 19 months for SOC and an HR of 0.85 (95% CI, 0.72–1.01; P = .058). For overall survival, the median was 74 months vs 68 months with SOC, for an HR of 0.86 (95% CI, 0.70–1.06; P = .159).
Notably, there were no major differences across groups with regard to grade 3–5 toxicities. Cardiac disorders, a major concern with COX-2 inhibitors, were seen in 3% of each of the three groups. The study did, however, exclude patients with significant cardiac problems, which may have lessened any potential effects.
James said that “at the very least we feel this data merits further evaluation, particularly because these drugs are widely used and widely available.”
The discussant for the session, A. Oliver Sartor, MD, of Tulane University Cancer Center in New Orleans, said that he doubted there will be attempts to replicate these results going forward. “I just suspect this combination is unlikely to become standard of care going forward,” he said.