Docetaxel added to standard of care extends survival in metastatic prostate cancer

Docetaxel should be added to standard care for men with metastatic, treatment-naive, hormone-sensitive prostate cancer, according to the results of a systemic review and meta-analysis.

However, it remains unclear whether the addition of docetaxel to standard care for men with localized prostate cancer is appropriate, researchers wrote.

Standard first-line therapy for men with locally advanced or metastatic prostate cancer consists of surgical castration through bilateral orchiectomy, or androgen deprivation therapy with luteinizing hormone-releasing hormone agonists or antagonists.

Claire L. Vale, PhD, senior research scientist in the MRC Clinical Trials Unit at University College London, and colleagues conducted a systemic review and meta-analysis of data from randomized controlled trials designed to evaluate the effects of adding docetaxel or bisphosphonates to standard treatment for men with high-risk localized or metastatic prostate cancer.

The researchers used medical databases — including MEDLINE, Embase, LILACS and the Cochrane Central Register for Controlled Trials — as well as conference proceedings, review articles and reference lists to identify relevant trials.

They extracted the HRs for the effects of docetaxel or bisphosphonates on survival — defined as the time from randomization until death from any cause — and failure-free survival, defined as the time from randomization to biochemical or clinical failure or death from any cause.

The researchers identified five eligible trials of docetaxel in men with metastatic disease. Results from three trials (n = 2,992) showed a survival benefit in the addition of docetaxel to standard of care (HR = 0.77; 95% CI, 0.68-0.87). The HR translated to an absolute improvement in 4-year survival of 9% (95% CI, 5-14).

Further, the addition of docetaxel conferred an improvement in failure-free survival (HR = 0.64; 95% CI, 0.58-0.7), translating to a 4-year absolute improvement of 16% (95% CI, 12-19).

Researchers identified 11 trials of docetaxel in men with locally advanced disease.

The results of three trials (n = 2,121) did not demonstrate a survival benefit (HR = 0.87; 95% CI, 0.69-1.09). However, results of four others (n = 2,348) suggested docetaxel conferred a significant benefit with regard to failure-free survival (HR = 0.7; 95% CI, 0.61-0.81), resulting in an absolute reduction of 4-year failure of 8% (95% CI, 5-10).

Vale and colleagues identified seven trials that evaluated bisphosphonates in men with metastatic disease.

Survival results from three of these trials (n = 2,740) suggested a survival benefit (HR = 0.88; 95% CI, 0.79-0.98). The HR translated to a 5% (95% CI, 1-8) absolute survival improvement. However, these findings were influenced considerably by the positive results of a trial that evaluated use of sodium clodronate.

The researchers observed no benefit from the addition of zoledronic acid, calculating an HR of 0.94 (95% CI, 0.83-1.07) and an absolute survival improvement of 2% (95% CI, -3 to 7).

The researchers reviewed 17 trials of bisphosphonate use in men with locally advanced disease. Results of four of these trials (n = 4,079) showed no evidence of benefit from the addition of bisphosphonates (HR = 1.03; 95% CI, 0.89-1.18) or zoledronic acid (HR = 0.98; 95% CI, 0.82-1.16).

The researchers did not conduct a formal meta-analysis of failure-free survival in this patient population due to the inconsistency of available data.

The researchers acknowledged limitations of their study, including the lack of published survival data in several studies identified by the researchers.

“For men with metastatic prostate cancer starting therapy for the first time, we found strong evidence to support the addition of docetaxel to androgen deprivation therapy as a new standard of care, and this combination should be offered to men who are fit to receive chemotherapy,” Vale and colleagues wrote. “More reliable evidence of the effect of docetaxel on OS and disease-specific survival is still needed in the localized setting and will be achieved through our planned collaborative international meta-analysis of individual participant data. ... Although additional trials are yet to be reported, the suggestion from our analyses is that any likely benefit of zoledronic acid will probably be small and not clinically meaningful.” – by Cameron Kelsall

Disclosure: Medical Research Council U.K. provided funding for this study. Vale reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.