Combination therapy linked to longer OS vs ADT in veterans with mHSPC

Data published in JAMA Network Open suggest that the use of combination therapy in veterans with de novo metastatic-hormone sensitive prostate cancer (mHSPC) has increased over time and is associated with significantly longer overall survival (OS) vs androgen-deprivation therapy (ADT) monotherapy.^1,2

In both high- and low-volume disease, combination therapy with an ARPI was associated with a longer PFS vs combination therapy with docetaxel.

"Frequently new drugs work [well] in clinical trials and have little effect in the real world. In most clinical trials patients are younger (age 65-70) and predominantly White (<4% Black men) who can travel to high-end academic medical centers and are more physically fit," explained lead author Martin W. Schoen, MD, MPH, of Saint Louis University and St. Louis Veterans Affairs Medical Center, in correspondence with Urology Times^®. "Our data comes from the entire VA, which includes ~25% Black men and men who are age 70-75 with heart disease, diabetes, etc. We show that in a real world population, the new therapies are effective. This study shows that the benefits of therapies in clinical trials is translating to benefits in the real world in a large group of patients."

In total, the retrospective cross-sectional study assessed 6216 veterans who received a diagnosis of de novo mHSPC from January 2013 to December 2022. The mean age of patients was 73.9 years (SD, 9.7). Among the 6216 patients included in the analysis, 3839 (61.8%) received ADT monotherapy, 1719 (27.7%) received an ARPI combination, and 658 (10.6%) received a docetaxel combination.

Overall, data showed an increase in the use of combination therapy over time, with combination treatment with either an ARPI or docetaxel becoming the majority of treatment in 2020. In 2020, combination therapy was used in 54% of patients (344 of 637), which rose to 63.1% of patients (465 of 737) in 2022.

Combination therapy was also associated with a significantly longer OS vs ADT monotherapy. Specifically, the mean OS was 40.3 months with combination therapy compared with 33 months with ADT monotherapy (HR, 0.80; 95% CI, 0.74 to 0.87).

There was no difference in OS between ARPI-based and docetaxel-based combination regimens. The mean OS was 40.4 months with ARPI combination therapy vs 40.2 months with docetaxel combination therapy (HR, 1.06; 95% CI, 0.92 to 1.22).

The study also assessed outcomes among 1540 patients who received combination therapy and had imaging reports for volume of disease. Those with high-volume disease demonstrated a significantly shorter survival; the mean OS was 33.3 months among those with high-volume disease compared with 62.5 months among those with low-volume disease (HR, 0.51; 95% CI, 0.43 to 0.60; P < .001).

Patients with high-volume disease were also more likely to receive combination therapy with docetaxel. Overall, 33.8% of patients with high-volume disease received docetaxel combination therapy vs 22.1% of patients with low-volume disease (P < .001).

In patients with high-volume disease, data showed no difference in OS between those who received an ARPI combination vs those who received a docetaxel combination. Specifically, OS was 32.2 months among those who received an ARPI combination vs 34.7 months among those who received a docetaxel combination (HR, 1.06; 95% CI, 0.91 to 1.23).

However, in those with high-volume disease, combination therapy with an ARPI was associated with a longer progression-free survival (PFS) vs combination therapy with docetaxel. The mean PFS was 18.7 months with an ARPI combination vs 16.0 months with a docetaxel combination (HR, 0.80; 95% CI, 0.70 to 0.91).

Trends were similar in patients with low-volume disease. Data showed no difference in OS between those who received an ARPI vs docetaxel regimen (68.4 months vs 55.3 months; HR, 0.81; 95% CI, 0.58 to 1.13), but PFS was significantly longer among those who received an ARPI regimen. Specifically, the mean PFS was 39.7 months in those who received an ARPI combination vs 24.0 months in those who received a docetaxel regimen (HR, 0.57; 95% CI, 0.43 to 0.76).

"This research shows that these drugs have a dramatic effect on average patients in the VA, a group that is hard to treat," Schoen added. "This is the first large study that I am aware of that has compared chemotherapy vs hormonal therapies in matched patients in routine clinical practice."

The authors also concluded, “The data presented here suggest that an ARPI doublet combination treatment that avoids chemotherapy is a standard of care, and there is little evidence of benefit associated with a docetaxel doublet compared with an ARPI doublet."

“Future research into the role of docetaxel in triple combination is needed to elucidate the benefit of chemotherapy in mHSPC," they added.

REFERENCES

1. Schoen MW, Doherty J, Eaton D, et al. Treatment patterns and survival among veterans with de novo metastatic hormone-sensitive prostate cancer. JAMA Netw Open. 2025;8(5):e259433. doi:10.1001/jamanetworkopen.2025.9433

2. Treatment patterns, survival among veterans with de novo metastatic hormone-sensitive prostate cancer. News release. Saint Louis University. May 7, 2025. Accessed May 27, 2025. https://www.newswise.com/articles/treatment-patterns-survival-among-veterans-with-de-novo-metastatic-hormone-sensitive-prostate-cancer