A groundbreaking study has revealed that the use of granulocyte colony stimulating factor (G-CSF) and dose modification of docetaxel significantly improved patient outcomes in the treatment of metastatic hormone-sensitive prostate cancer (mHSPC). This modified approach allowed 97% of patients to receive an effective dose of docetaxel—defined as a relative dose intensity (RDI) greater than 80%—when combined with androgen deprivation therapy and darolutamide (Nubeqa) or a placebo. These findings were presented at the ASCO 2025 Genitourinary Cancers Symposium.
According to the research, G-CSF use predominantly occurred after the first dose of docetaxel, serving as secondary prophylaxis. The study aimed to evaluate the impact of docetaxel dose intensity and G-CSF use on the safety and efficacy of this therapy regimen.
Key Trial Findings
In the ARASENS trial, involving 1279 patients with mHSPC, 98.3% of patients in the darolutamide group achieved an RDI of greater than 80%, while 89.2% had an RDI of more than 85%, and 82.4% had an RDI exceeding 90%. In the placebo group, the rates were 97.6%, 88.4%, and 81.4%, respectively. Notably, the presence of darolutamide did not influence the docetaxel dose intensity received.
G-CSF Utilization
Dose modification of docetaxel was necessary for 800 patients (63%), with 556 patients (43%) requiring G-CSF for secondary prophylaxis. Among those undergoing dose modification, 47% received G-CSF. Importantly, the addition of darolutamide did not increase the need for G-CSF or docetaxel modification.
The study further broke down G-CSF usage within subgroups based on RDI levels and treatment assignment (darolutamide or placebo). In patients receiving darolutamide, those with an RDI of greater than 85% had similar G-CSF usage rates compared to those with an RDI of 85% or less.
Geographic Variations in G-CSF Use
Overall, patients with a lower RDI (85% or less) were more likely to use G-CSF compared to those with an RDI of greater than 85%. The use of G-CSF was particularly high in the Asia Pacific region, with 69.6% of patients in the darolutamide group with an RDI of 85% or less requiring G-CSF, compared to 39.4% with an RDI of over 85%. In contrast, North American patients showed a smaller difference, with 25% and 31% in the darolutamide group having lower and higher RDI, respectively.
Survival and Progression Data
The survival analysis indicated that overall survival (OS) was similar in both the darolutamide and placebo groups after 24 weeks, regardless of the docetaxel RDI. Median OS was not reached in both docetaxel RDI groups within the darolutamide group, exhibiting an HR of 1.41. In the placebo group, median OS was not reached for those with a lower RDI, while it was 45.8 months for those with a higher RDI, with an HR of 1.17.
Similarly, the time to prostate-specific antigen progression (TTPSA) was consistent between patients receiving darolutamide and placebo, irrespective of their docetaxel RDI. The median TTPSA was not reached in both RDI groups for darolutamide recipients, while it was 21.7 months for those with a lower RDI and 19 months for those with a higher RDI in the placebo group.
Patients’ Baseline Characteristics
Baseline characteristics were generally consistent across treatment groups, except for regional differences. For example, patients with an ECOG performance status of 0 were more prevalent in those with higher RDI in both treatment arms. Baseline factors also included initial diagnosis Gleason score, median prostate-specific antigen concentration, median alkaline phosphatase, and whether the disease was de novo or recurrent.
Safety Profile
The study reported low rates of docetaxel discontinuation across all groups. For patients with a lower RDI using darolutamide, 7.2% discontinued docetaxel, while 92.8% required dose modification. Higher RDI patients with darolutamide had an 8.1% discontinuation rate and 26% required dose adjustment. In the placebo group, patients with a lower RDI had a 10.8% discontinuation rate, with 97.3% needing dose modification, compared to 10.5% and 25.3% in patients with a higher RDI.
Grade 3 or greater treatment-related adverse events (TRAEs) were more frequent in patients with a lower docetaxel RDI. Neutropenia was reported in 66.7% of darolutamide recipients versus 70.3% of placebo patients, and febrile neutropenia in 21.6% and 17.6% respectively. Importantly, almost all instances of febrile neutropenia were grade 3, with 91.3% of patients affected.
Despite high TRAE rates, the overall discontinuation rates were low, indicating that appropriate use of G-CSF enabled effective docetaxel administration and that darolutamide did not negatively impact docetaxel tolerance.
Implications and Future Directions
These results highlight the importance of dose modification and G-CSF use in ensuring adequate and safe docetaxel treatment for patients with mHSPC. The study underscores that while TRAEs are common, they are manageable. Future research could focus on refining G-CSF dosing strategies to further minimize adverse effects while maintaining high treatment efficacy.
For healthcare providers and patients alike, these findings provide valuable insights that could improve treatment outcomes and quality of life for individuals with metastatic hormone-sensitive prostate cancer.
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