October 22, 2023
Early Darolutamide Treatment Yields Significant Responses in Metastatic Prostate Cancer
By Dibash Kumar Das, PhD
New research from the ARASENS clinical trial has unveiled promising results regarding prostate-specific antigen (PSA) outcomes in patients with metastatic hormone-sensitive prostate cancer (mHSPC). The study explored the effects of darolutamide (DARO) in combination with androgen-deprivation therapy (ADT) and docetaxel (DOC) on patients with both high-volume (HV) and low-volume (LV) mHSPC. The study was presented at the ESMO 2023 Congress, held in Madrid, Spain (Abstract 1784P).
ARASENS previously gained recognition for its significant achievement in reducing the risk of death (N Engl J Med 2022; doi: 10.1056/NEJMoa2119115). “In ARASENS, DARO in combination with ADT and chemotherapy DOC significantly reduced risk of death in patients with mHSPC by 32.5 percent, compared to ADT and chemotherapy DOC alone,” emphasized study author Fred Saad, MD, FRSC, Professor in the Department of Surgery and the Raymond Garneau Chair in Prostate Cancer at the Université de Montréal in Quebec, Canada.
The post hoc analysis also revealed that overall survival (OS) outcomes were strikingly similar for patients with HV and LV disease. These findings prompted a closer examination of PSA outcomes within these patient subgroups.
In this clinical trial, patients with mHSPC were randomly assigned to receive either DARO 600 mg twice daily or a placebo alongside ADT and DOC. PSA levels were monitored at regular intervals. The study aimed to assess the proportion of patients who achieved undetectable PSA levels (less than 0.2 ng/mL) and their time to PSA progression. Additionally, researchers explored the association between achieving undetectable PSA levels and time to PSA progression and OS.
The results based on a cohort of 1,305 patients were striking. Patients who received DARO exhibited a rapid, deep, and durable PSA response. A notable achievement was the early response observed as soon as 12 weeks into the treatment. In the HV subgroup, 43.1 percent of patients on DARO achieved an undetectable PSA at 24 weeks, compared to only 21.7 percent in the placebo group. Similarly, in the LV subgroup, 66.9 percent of patients on DARO reached an undetectable PSA level at 24 weeks, compared to 31.5 percent on placebo.
The benefits continued to increase over time, with significantly more patients on DARO achieving undetectable PSA levels at 52 weeks and, indeed, at any time throughout the trial. Notably, time to PSA progression was prolonged in patients who received DARO compared to the placebo group, both in the HV and LV subgroups.
The improvement in time to PSA progression was notable, with HRs of 0.30 in HV patients and HR of 0.09 in LV patients. These results translated into 4-year PSA progression-free rates of 65.8 percent for HV patients and 91.7 percent for LV patients in the DARO group.
Perhaps most encouraging was the finding that patients who achieved undetectable PSA levels through DARO treatment experienced significant improvements in time to PSA progression and OS compared to those who did not. This was seen across both HV and LV subgroups, with HRs reflecting this substantial advantage. “No notable adverse events were associated with this regimen and there were no new significant additional toxicities noted,” Saad noted.
In light of the study's results, the implications for real-world clinical practice in managing mHSPC, encompassing both high-volume and low-volume cases, are compelling. Saad's conclusions emphasize the potential impact of early treatment intensification using DARO in combination with ADT and chemotherapy DOC.
“Early treatment intensification with darolutamide in combination with ADT and chemotherapy docetaxel allows patients with high- and low-volume mHSPC to achieve rapid, deep, and durable PSA responses that are associated with improved time to PSA progression and overall survival,” Saad noted. “In fact, the PSA rates achieved in the low-risk/volume patients are among the highest ever seen and these patients have excellent long-term clinical outcomes.
“Furthermore, undetectable PSA levels have been associated with several positive disease outcomes, including metastasis-free survival and overall survival in prostate cancer. These latest post-hoc findings from ARASENS confirm darolutamide’s value in treating patients with mHSPC across volume of disease,” Saad concluded.
Dibash Kumar Das is a contributing writer.