Longer continuous docetaxel treatment confers OS benefit in prostate cancer

A greater number of docetaxel cycles improved OS in men with metastatic castration-resistant prostate cancer, according to a post-hoc analysis of the phase 3 Mainsail trial.

“Docetaxel combined with prednisone is the current first-line chemotherapy for metastatic castration-resistant prostate cancer,” Ronald de Wit, MD, PhD, group leader for experimental systemic therapies for urogenital cancer at Erasmus MC Cancer Institute in Rotterdam, Netherlands, and colleagues wrote. “To date, the optimal number of docetaxel cycles has not been established.”

The Mainsail trial — which closed early due to futility — evaluated the addition of lenalidomide (Revlimid, Celgene) to docetaxel and prednisone. Results showed that the addition of lenalidomide led to inferior OS and increased incidence of toxic events.

The experimental arm of the Mainsail trial included six cycles of docetaxel, whereas the control arm included eight cycles. de Wit and colleagues sought to determine whether the cumulative dose of docetaxel — reflected by the total number of cycles administered — contributed to the OS difference.

The study included data from 1,059 men (median age, 69 years; range, 43-90), who received treatment until disease progression or unacceptable toxicity.

The researchers performed additional univariate and multivariate analyses on the intention-to-treat population. Sensitivity analyses excluded patients who ceased treatment due to disease progression and those who completed fewer than five cycles of treatment.

Whether the total number of docetaxel cycles acted as an independent factor for OS served as the study’s primary outcome measure.

The experimental arm included 244 men who received eight or more cycles of docetaxel and 289 men who received fewer than eight cycles. The control arm included 296 men who received eight or more cycles and 230 men who received fewer than eight cycles.

A univariate analysis showed an association between improved OS and a greater number of docetaxel cycles (P < .001), cumulative docetaxel dose (P < .001), lenalidomide duration (P < .001) and allocated treatment arm (P = .03).

Results of a multivariate analysis showed fewer than eight cycles vs. more than eight cycles was associated with poorer OS (HR = 1.9; 95% CI, 1.66-2.19), regardless of treatment arm (HR for docetaxel and prednisone vs. lenalidomide, docetaxel and prednisone = 1.06; 95% CI, 0.92-1.21).

A sensitivity analysis showed that continuous docetaxel treatment beyond four cycles served as an independent prognostic factor for improved OS, regardless of treatment arm. Median OS was 33 months among patients who received 10 or more cycles, compared with 26.9 months for patients who received eight to 10 cycles, and 22.8 months for patients who received five to seven cycles (P < .001).

Longer continuous treatment — evaluated according to 10 or more cycles, eight to 10 cycles, and five to seven cycles — remained predictive of better OS when analyzed by treatment arm (experimental, 31.6 months vs. 24.4 months vs. 18.8 months; control, 34.7 months vs. 29.7 months vs. 23.6 months).

The researchers identified the post-hoc study design as a potential limitation.

“These data indicate that patients who appear to have clinical, radiological or biochemical benefit by docetaxel should continue beyond six cycles as long as they tolerate their treatment well,” de Wit and colleagues wrote. “A prospective study, potentially in the setting of metastatic hormone-sensitive prostate cancer, may lend further prospective evidence.” – by Cameron Kelsall

Disclosure: The study was funded by Celgene. de Wit reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.