KEY TAKEAWAYS
- The ARASENS phase 3 study analyzed the impact of DARO combined with ADT and docetaxel in metastatic hormone-sensitive prostate cancer pts vs. only ADT and docetaxel.
- The study confirmed that mHSPC patients who were administered DARO, ADT, and docetaxel experienced lasting, deep drops in PSA levels.
In the ARASENS study, the combination of darolutamide (DARO) with androgen-deprivation therapy (ADT) and docetaxel reduced the death risk by 32.5% (HR 0.68; 95% CI 0.57–0.80; P<0.0001) compared to just ADT + docetaxel in patients (pts) having metastatic hormone-sensitive prostate cancer (mHSPC). This report presented data on prostate-specific antigen (PSA) outcomes from ARASENS.
The study involved mHSPC pts, who were equally divided to receive either DARO 600 mg twice daily or a placebo (PBO), along with ADT + docetaxel. Serum PSA was checked at the beginning and every 12 weeks. The study assessed the cases of undetectable PSA (<0.2 ng/mL), ≥50% and ≥90% PSA reductions from baseline (PSA50, PSA90), and times to PSA progression and PSA50/PSA90. Later analyses examined how undetectable PSA at 24 and 36 weeks influenced overall survival (OS) and time to PSA progression.
Of the 1305 patients analyzed (DARO, 651; PBO, 654), the average PSA levels at the start were 30.3 and 24.2 ng/mL, respectively. Those on DARO showed a swift 90% PSA drop, with 67.6% achieving this within 12 weeks, 82.0% in 24 weeks, and 84.9% at any given time. This contrasts with 42.8%, 54.4%, and 59.0% in the PBO group. DARO led to a significant PSA reduction, with the lowest median PSA being 0.020 ng/mL, compared to 0.495 ng/mL for PBO. Over double the number of DARO pts had undetectable PSA at 24 weeks (48.7% vs 23.9%), which grew at 36 and 52 weeks (57.1% and 60.2%). Those DARO pts with undetectable PSA at 24 and 36 weeks saw enhanced overall survival (with specific ratios) and extended time before PSA rise, indicating a consistent PSA response.
The study showed that mHSPC patients on DARO + ADT + docetaxel witnessed rapid, sustained, and deep PSA responses. This is linked with better overall survival and extended time to PSA progression when contrasted with PBO + ADT + docetaxel.
Source: https://www.auajournals.org/doi/10.1097/JU.0000000000003257.01
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT02799602
Saad, Fred; Tombal, Bertrand; Hussain, Maha; Fizazi, Karim; Sternberg, Cora N.; Crawford, E. David; Nordquist, Luke T.; Tutrone, Ronald; Shore, Neal D.; Belkoff, Laurence; Kapur, Shivani; Jhaveri, Jay; Ortiz, Jorge; Srinivasan, Shankar; Verholen, Frank; Smith, Matthew R. MP29-01 RAPID, DURABLE, AND DEEP PROSTATE-SPECIFIC ANTIGEN RESPONSE FOLLOWING ADDITION OF DAROLUTAMIDE TO ANDROGEN-DEPRIVATION THERAPY AND DOCETAXEL IN ARASENS, Journal of Urology: April 2023 – Volume 209 – Issue Supplement 4 doi: 10.1097/JU.0000000000003257.01
