Presenting Author: Kirollos Hanna, PharmD, BCPS, BCOP, FACCC, FAPO, FHOPA, Mayo Clinic College of Medicine, Rochester, MN, and Minnesota Oncology, St. Paul, MN
BACKGROUND: In the ARANOTE study,1 darolutamide plus androgen-deprivation therapy (ADT) reduced the risk for radiologic progression or death versus placebo plus ADT by 46% (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.41-0.71; P<.0001) in patients with metastatic hormone-sensitive prostate cancer (mHSPC).
OBJECTIVE: To report ARANOTE’s post-hoc analyses correlating prostate-specific antigen (PSA) response with overall outcomes and by baseline PSA level.
METHODS: Patients with mHSPC were randomized 2:1 to darolutamide 600 mg twice daily plus ADT or to placebo plus ADT. The achievement of undetectable PSA (<0.2 ng/mL) at any time was evaluated. Radiologic progression-free survival, the time to metastatic castration-resistant prostate cancer (mCRPC), and the time to PSA progression were evaluated in patients who did or did not achieve PSA <0.2 ng/mL and by baseline PSA group, which was defined as lower than the first quartile (quartile 1, <4.1 ng/mL), between quartile 1 and the median (4.1-<21.3 ng/mL), and equal to or higher than the median (≥21.3 ng/mL).
RESULTS: In 669 patients (darolutamide, 446; placebo, 223), the median baseline PSA was 21.4 and 21.2 ng/mL, respectively. More patients receiving darolutamide achieved a PSA of <0.2 ng/mL (62.6%) versus those receiving placebo (18.5%). Patients achieving a PSA of <0.2 ng/mL at any time in both groups had lower ECOG performance status and baseline PSA values than those who did not. Patients receiving darolutamide achieved a PSA of <0.2 ng/mL versus those who did not have lower risk for radiologic progression or death (81%, HR, 0.19; 95% CI, 0.13-0.27), progression to mCRPC (84%, HR, 0.16; 95% CI, 0.12-0.23), and PSA progression (92%, HR, 0.08; 95% CI, 0.05-0.12), which indicates a durable response. Regardless of the baseline PSA group, more patients receiving darolutamide versus placebo achieved a PSA of <0.2 ng/mL at any time, with higher rates of PSA of <0.2 ng/mL in patients with a low baseline PSA of <4.1 ng/mL (darolutamide, 87.6% vs placebo, 43.5%; 4.1-<21.3 ng/mL, 64.8% vs 14%; ≥21.3 ng/mL, 50.5% vs 10.2%). Patients receiving darolutamide with a low baseline PSA (<4.1 ng/mL) had a longer time to radiologic progression or death, time to mCRPC, and time to PSA progression versus patients with a baseline PSA of ≥21.3 ng/mL; outcomes were similar for patients with a baseline PSA of 4.1 to <21.3 ng/mL versus ≥21.3 ng/mL. Safety with darolutamide was consistent with previous data and was independent of PSA response or baseline PSA. Patients who received darolutamide had lower rates of discontinuation as a result of TEAEs than patients who received placebo.
CONCLUSION: More patients receiving darolutamide achieved undetectable PSA at any time versus placebo, regardless of baseline PSA. Undetectable PSA response with darolutamide correlated with clinical benefit in terms of radiologic progression or death and longer times to mCRPC and PSA progression.
- Saad F, Vjaters E, Shore N, et al. Darolutamide in combination with androgen-deprivation therapy in patients with metastatic hormone-sensitive prostate cancer from the phase III ARANOTE trial. J Clin Oncol. 2024;42:4271-4281.