Update Sustains OS Benefit of Chemohormonal Therapy in High-Volume Prostate Cancer

Adding docetaxel to androgen-deprivation therapy (ADT) improved overall survival (OS) by nearly 17 months in men with high-volume metastatic hormone-sensitive prostate cancer. Investigators for the multicenter phase III CHAARTED trial noted that the survival benefit did not extend to men with low-volume disease.¹

In this updated analysis, the median OS was 57.6 months for the chemohormonal therapy arm versus 47.2 months for ADT alone (hazard ratio [HR], 0.72; 95% CI, 0.59-0.89; P = .0018) at a median follow-up of 53.7 months. For patients with high-volume disease (n = 513), the median OS was 51.2 months with chemohormonal therapy versus 34.4 months with ADT alone (HR, 0.63; 95% CI, 0.50-0.79; P <.001).

Investigators confirmed the clinical benefit observed with chemohormonal therapy regardless of whether they had relapsed after prior local therapy of the prostate with or without curative intent.

There was no OS benefit observed for men with low-volume disease (n = 277; HR, 1.04; 95% CI, 0.70-1.55; P = .86).

A total of 790 patients were randomly assigned to either ADT plus docetaxel every 3 weeks for 6 cycles (n = 397) or ADT alone (n = 393) from July 2006 to November 2012. Stratification was performed prospectively according to high or low burden of metastatic disease.

Median age for the combination group was 64 years and 63 years among patients receiving ADT alone. Additionally, about 65% of patients had high-volume disease, approximately 60% had a Gleason score of 8 or higher, and 73% of patients had received no prior local therapy for prostate cancer.

This report represents data with a cutoff date for survival of April 23, 2016.

At the time of this analysis, there were 188 deaths in the combination arm and 211 deaths in the ADT alone arm.

The time to castration-resistant prostate cancer (CRPC) was 19.4 months in the combination arm versus 11.7 months in the ADT alone arm (HR, 0.61; 95% CI, 0.52-0.73; P <.001). For high-volume disease, the median time to CRPC was 14.9 months (HR, 0.58; 95% CI, 0.47-0.71; P <.001) for the combination arm versus 8.6 months for the ADT alone arm. For low-volume disease, it was 31.0 months for the combination arm versus 22.7 months for the ADT alone arm (HR, 0.70; 95% CI, 0.50-0.96; P = .03).

The median time to clinical progression also favored the combination arm, 33.0 months versus 19.8 months (HR, 0.62; 95% CI, 0.51-0.75; P <.001). As with survival, patients with high-volume disease had superior outcomes (27.3 vs 13.0 months; HR, 0.53; 95% CI, 0.42-0.67; P <.001).

Patients with low-volume disease did not derive a similar benefit. The median time to clinical progression was 42.5 months in the combination arm versus 44.3 months in the ADT alone arm (HR, 0.86; 95% CI, 0.6-1.25; P = .43).

These updated results confirm findings first presented at the 2014 ASCO Annual Meeting and published in 2015, which showed that the chemohormonal combination could extend OS.² The median OS with the combination was 57.6 versus 44.0 months with ADT alone (HR, 0.61; 95% CI, 0.47-0.80; P <.001).

In patients with high-volume disease, the median OS was 49.2 months with the combination versus 32.2 months with ADT alone (HR, 0.60; 95% CI, 0.45-0.81; P <.001) in the previously reported results. In patients with low-volume disease, the median OS had not yet been reached at the time of the analysis (HR, 0.60; 95% CI, 0.32-1.13; P = .11).

References

1. Kyriakopoulos CE, Chen Y, Carducci MA, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer: long-term survival analysis of the randomized phase III E3805 CHAARTED trial [published online January 31, 2018]. J Clin Oncol. doi: 10.1200/JCO.2017.75.3657.
2. Sweeney CJ, Chen YH, Carducci M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med. 2015; 373:737-46. doi: 10.1056/NEJMoa1503747.