Amongst sufferers with hormone-sensitive prostate most cancers, another dosing routine of docetaxel — 50 mg/m2 as soon as each two weeks as a substitute of 75 mg/m2 as soon as each three weeks — plus Nubeqa (darolutamide) and androgen deprivation remedy (ADT) was related to statistically important and clinically significant enhancements in extreme, life-threatening and deadly aspect impact charges as nicely neutropenia and demise of any cause, research outcomes have proven.
The findings, from the part 3 ARASAFE research, had been offered on the 2025 European Society for Medical Oncology Congress in Berlin by Dr. Marc-Oliver Grimm, professor and chair of urology at Jena College Hospital in Jena, Germany.
By the use of background, Grimm defined that the usage of ADT, Nubeqa and docetaxel is FDA authorised for sufferers with mHSPC primarily based on findings from the part 3 ARASENS trial. In that routine, the docetaxel dosage is 75 mg/m2 as soon as each three weeks. Nevertheless, Grimm identified that toxicity reminiscent of neutropenic problems may restrict the usage of this routine in contrast with androgen receptor pathway inhibitor/ADT doublet remedy. For ARASAFE, Grimm and his co-authors sought to judge toxicity in triplet remedy with Nubeqa/ADT/docetaxel with docetaxel dosages of fifty mg/m2 as soon as each two weeks and 75 mg/m2 as soon as each three weeks.
Glossary
Neutropenia: a situation the place the variety of neutrophils (a kind of white blood cell that helps combat infections) is decrease than regular. This could make it simpler to get infections.
General Survival: the size of time from the beginning of therapy that sufferers are nonetheless alive. It’s a method medical doctors measure how nicely a therapy works.
Leukopenia: a situation the place there are fewer white blood cells than regular. White blood cells assist defend the physique from infections.
Prostate-Particular Antigen (PSA): a protein made by the prostate gland. PSA ranges are sometimes checked with a blood check to assist detect or monitor prostate most cancers.
“We hypothesized that triplet remedy with [Nubeqa], ADT and 50 mg[/m2] each two weeks reduces grade 3 (extreme) to five (deadly) adversarial occasions in comparison with the usual 75-mg[/m2] schedule,” Grimm mentioned. Grimm additionally pointed to earlier analysis indicating that ADT plus docetaxel 50 mg/m2 as soon as each two weeks was related to higher time to therapy failure and fewer grade 3 to 4 (life-threatening) negative effects in sufferers with metastatic castration-resistant prostate most cancers.
In ARASAFE, a complete of 250 sufferers with mHSPC had been randomly assigned to Nubeqa 600 mg twice every day plus ADT plus six cycles of docetaxel 75 mg/m2 as soon as each three weeks (three-week cycle, 129 sufferers) or to Nubeqa 600 mg twice every day plus ADT plus six cycles of docetaxel 50 mg/m2 as soon as each two weeks (four-week cycle, 121 sufferers). Complete anticipated docetaxel dose was 450 mg/m2 within the 75 mg/m2 arm versus 600 mg/m2 within the 50 mg/m2 arm.
Main finish factors included grade 3 to five negative effects and grade 3 to 4 neutropenia or demise of any cause. Secondary finish factors included time to castration-resistant prostate most cancers, total survival, time to ache development, time to first symptomatic skeletal occasion, time to initiation of subsequent systemic antineoplastic remedy, time to worsening of disease-related bodily signs and high quality of life.
Median age at baseline was 68 years within the 75 mg/m2 arm versus 67 years within the 50 mg/m2 arm. Excessive-volume illness was current in 108 (83.7%) sufferers within the 75 mg/m2 arm versus 104 (86%) sufferers within the 50 mg/m2 arm. Imply variety of docetaxel doses was 5.6 within the 75 mg/m2 arm versus 10.7 within the 50 mg/m2 arm. Imply cumulative docetaxel dose was 842.8 mg within the 75 mg/m2 arm versus 1073.5 mg within the 50 mg/m2 arm.
Grimm reported that the research reached its major finish factors: The grade 3 to five aspect impact price was 78.9% within the 75 mg/m2 arm versus 61.2% within the 50 mg/m2 arm. Moreover, the grade 3 to 4 neutropenia/demise of any cause price was 64.1% within the 75 mg/m2 arm versus 24% within the 50 mg/m2 arm.
Grimm additionally reported that the charges of neutropenia, leukopenia and febrile neutropenia favored the 50 mg/m2 dosage over the 75 mg/m2 dosage.
The investigators utilized prostate-specific antigen (PSA) response at week 26 as a putative surrogate for oncologic end result. Grimm reported that the median PSA degree within the 75 mg/m2 arm was 0.16 ng/mL versus 0.26 ng/mL within the 50 mg/m2 arm. PSA ranges of 0.2 ng/mL or decrease had been noticed in 63 (48.8%) sufferers within the 75 mg/m2 arm versus 50 (41.3%) sufferers within the 50 mg/m2 arm.
“In abstract, ARASAFE demonstrates a statistically extremely important and clinically significant discount within the incidence of grade 3 to five [side effect] price and the speed of grade 3 to 4 neutropenia or demise no matter cause for the experimental method. This was achieved regardless of increased complete doses of docetaxel within the experimental arm. Due to this fact, the ARASAFE method could also be thought of a possible new commonplace of care,” Grimm mentioned in his concluding remarks.
REFERENCES
- “3-weekly docetaxel 75 mg/m2 vs 2-weekly docetaxel 50 mg/m2 together with darolutamide + ADT in sufferers with mHSPC: Outcomes from the randomised part III ARASAFE trial,” by Dr. Marc-Oliver Grimm, et al. Offered at: European Society for Medical Oncology Congress. October 17-21, 2025. Berlin, Germany. LBA92.
- “FDA approves darolutamide tablets for metastatic hormone-sensitive prostate most cancers,” FDA; https://www.fda.gov/medicine/resources-information-approved-drugs/fda-approves-darolutamide-tablets-metastatic-hormone-sensitive-prostate-cancer
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