Docetaxel with Androgen Deprivation and Radiotherapy in High-risk Localized Prostate Cancer: An ICECaP Individual Patient Data Meta-analysis.

[BACKGROUND AND OBJECTIVE] The addition of docetaxel to radiotherapy (RT) and long-term androgen deprivation therapy (ADT) is not a standard of care for the treatment of high-risk localized prostate cancer (HRLPC). We performed an individual patient data (IPD) meta-analysis to assess the addition of docetaxel to RT and ADT in HRLPC.

[METHODS] IPD from patients with HRLPC (as defined by any of the following risk factors: Gleason score ≥8, prostate-specific antigen >20 ng/ml, cT3-T4, and/or N1) treated in trials evaluating RT + ADT ± docetaxel, available in the Intermediate Clinical Endpoints in Carcinoma of the Prostate (ICECaP) repository, were collated. The primary outcome was metastasis-free survival (MFS), and the secondary outcomes were overall survival (OS), event-free survival (EFS), prostate cancer-specific mortality (PCSM), and time to metastasis (TTM). Analyses were conducted using a one-stage IPD meta-analysis. Disease risk was defined as high (one risk factor) or very high (two to three risk factors and/or N1). Multivariable Cox proportional hazards and Fine-Gray competing risk models estimated the effect of addition of docetaxel to RT + ADT on each time-to-event outcome.

[KEY FINDINGS AND LIMITATIONS] A total of 1690 patients from four trials were included. Docetaxel did not lead to an overall benefit in MFS (hazard ratio [HR] 0.89), OS (HR 0.88), and TTM (HR 0.87), but there was a significant benefit in EFS (HR 0.87) and PCSM (HR 0.70). The 5- and 10-yr MFS rates were, respectively, 79% and 57% in patients treated with RT + ADT, and 84% and 62% in those who received RT + ADT + docetaxel. There was no clear evidence of a greater benefit of docetaxel in patients with very-high-risk disease than in those with high-risk disease (MFS: HR 0.87 vs 0.97; OS: HR 0.86 vs 0.95; EFS: HR 0.83 vs 0.93; TTM: HR 0.86 vs 0.92; and PCSM: HR 0.70 vs 0.73), with no statistically significant difference in treatment effect by risk group (all p-interaction >0.1).

[CONCLUSIONS AND CLINICAL IMPLICATIONS] Addition of docetaxel to RT + ADT did not lead to a significant benefit in MFS or OS. Clinical stratification together with biomarkers should be evaluated to determine whether biologic features can identify HRLPC patients who are more likely to benefit from intensification of therapy with docetaxel.