High burden prostate cancer patients benefit form androgen deprivation and Taxotere combination.
For patients with metastatic hormone-sensitive prostate cancer, metastatic burden affects outcome. We examined efficacy and safety from the ARASENS trial for subgroups by disease volume and risk.
Patients with metastatic hormone-sensitive prostate cancer were randomly assigned to darolutamide or placebo plus androgen-deprivation therapy and docetaxel. High-volume disease was defined as visceral metastases and/or ≥ 4 bone metastases with ≥ 1 beyond the vertebral column/pelvis. High-risk disease was defined as ≥ 2 risk factors: Gleason score ≥ 8, ≥ 3 bone lesions, and presence of measurable visceral metastases.
Of 1,305 patients, 1,005 (77%) had high-volume disease and 912 (70%) had high-risk disease. Darolutamide increased overall survival (OS) versus placebo in patients with high-volume (hazard ratio [HR], 0.69; 95% CI, 0.57 to 0.82), high-risk (HR, 0.71; 95% CI, 0.58 to 0.86), and low-risk disease (HR, 0.62; 95% CI, 0.42 to 0.90), and in the smaller low-volume subgroup, the results were also suggestive of survival benefit (HR, 0.68; 95% CI, 0.41 to 1.13). Darolutamide improved clinically relevant secondary end points of time to castrationresistant prostate cancer and subsequent systemic antineoplastic therapy versus placebo in all disease volume and risk subgroups. Adverse events (AEs) were similar between treatment groups across subgroups. Grade 3 or 4 AEs occurred in 64.9% of darolutamide patients versus 64.2% of placebo patients in the high-volume subgroup and 70.1% versus 61.1% in the low-volume subgroup. Among the most common AEs, many were known toxicities related to docetaxel.
In patients with high-volume and high-risk/low-risk metastatic hormonesensitive prostate cancer, treatment intensification with darolutamide, androgen-deprivation therapy, and docetaxel increased OS with a similar AE profile in the subgroups, consistent with the overall population.
We know that combination PARP and antiandrogen is better than antiandrogen alone. I have wondered if we need antiancrogen on those patients. This shows that, YES, we do. The combination also was better than PARP inhibitor monotherapy in those patients carrying HRRm.
It might be costly to get the PET scans but helps with prognosis and directing patients to palliative care since positive lesions in all predicts shorter overall survival.
The role for immunotherapy in combination with multitargeted therapy in prostate cancer, for patients who had previous docetaxol, or had visceral disease (liver) showed more benefit from the combination vs. second novel hormonal therapy. Recall that patients who had exposure to docetaxol can be treated with pluvicto. Genomic and genetic testing is encouraged for those patients as PARP targeted mutations can be found (homologous recombination-repair mutations).
SBRT improves PFS in addition to antiandrogen therapy. The question is, with oligomets, do we need systemic therapy in all patients? Or will SBRT be sufficient?
I encourage our FCS radiation oncologists to provide their input on this study, as well.
Our radiation oncologists will find this article particularly interesting – more radiation is NOT better.
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