FROM JAMA ONCOLOGY
Extending docetaxel chemotherapy significantly improved overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC), regardless of whether they received lenalidomide, according to a retrospective analysis of 1,059 patients from a randomized, phase III trial.
“We found a robust and independent effect on overall survival by the number of docetaxel cycles administered in the setting of mCRPC,” wrote Ellen de Morree of Erasmus MC Cancer Institute (Rotterdam, the Netherlands) and her associates (JAMA Oncol. 2016 Aug 25. doi: 10.1001/jamaoncol.2016.3000 ).
The association was independent of performance status (Eastern Cooperative Oncology Group score) or baseline levels of lactate dehydrogenase level, hemoglobin, and albumin, they noted. “These data indicate that patients who appear to have clinical, radiological, or biochemical benefit by docetaxel should continue beyond 6 cycles as long as they tolerate their treatment well,” they concluded.
This study, the first to investigate the optimal number of docetaxel cycles in mCRPC, analyzed data from the multicenter Mainsail trial, in which patients received docetaxel, prednisone, and lenalidomide (DPL) or docetaxel, prednisone, and a placebo (DP) until they developed progressive disease or unacceptable adverse effects. Although dose intensity was similar between the two trial arms, DPL patients developed myelotoxicity with lenalidomide and therefore received a median of only six treatment cycles, while DP patients received a median of eight cycles. That difference enabled this analysis, the investigators noted.
Cumulative dose of docetaxel, duration of lenalidomide treatment, and allocated treatment regimen were significant predictors of overall survival in the univariate analysis. Overall survival was associated with treatment arm in a multivariable analysis that did not account for number of docetaxel cycles (hazard ratio, 1.6; 95% confidence interval, 1.2 to 2.1; P less than .001). But that changed after the addition of a number of docetaxel cycles to the model, the researchers said. In this final model, treatment with eight or more cycles of docetaxel led to substantially improved overall survival (hazard ratio, 1.9; P less than .001), regardless of lenalidomide treatment (HR, 1.1; 95% CI, 0.9 to 1.2; P = .4). Sensitivity analyses confirmed the association – patients who received more than 10 cycles of docetaxel had a median overall survival of 33 months (30-37 months), versus 27 months (24-30 months) with 8-10 cycles and about 23 months (18-27 months) with 5-7 cycles (P less than .001).
