Эффективность последовательной терапии энзалутамидом и доцетакселом сравнима с применением абиратерона в лечении рака простаты

Survival appears comparable whether docetaxel (DTX) treatment is preceded by enzalutamide (ENZ) or abiraterone acetate plus prednisolone (ABI) in men with castration-resistant prostate cancer (CRPC). Manabu Kamiyama, MD, PhD, of the University of Yamanashi Graduate School of Medical Sciences in Yamanashi, Japan, and colleagues reported these results from a subanalysis of the ENABLE trial in International Journal of Urology. Direct comparisons of ENZ-DTX vs ABI-DTX sequential therapy in CRPC have been limited. The ENABLE trial was an investigator-initiated randomized controlled trial conducted between 2015 and 2019. Men (N=184) with CRPC were randomly assigned to receive 160 mg ENZ (n=92) or 1000 mg ABI (n=92) daily with 10 mg prednisolone followed by the physician’s choice of therapy. In this subanalysis, the subset of men who received DTX after ENZ (n=20) or ABI (n=21) were evaluated for time to PSA progression (TTPP), defined as a PSA increase of at least 25% and at least 2 ng/mL above the nadir at week 13. The ENZ-DTX and ABI-DTX recipients comprised men aged a median 72 years with baseline PSA at diagnosis of 124.2 (range, 5.4-4730) and 67.9 (range, 0.9-1899) ng/mL, of whom 55% and 52% had regional lymph node metastasis, respectively.  The median TTPP was 7.1 months with ENZ-DTX and 4.1 months with ABI-DTX ( P =.1388) and radiographic progression-free survival (rPFS) was 12.0 months with ENZ-DTX and 7.0 months with ABI-DTX ( P =.1408) – both nonsignificant differences. Neither median overall survival (median, 22.7 vs 32.1 months; P =.2247) nor prostate cancer-specific survival (PCSS; median, 22.7 vs 32.1 months; P =.1724) differed between the ENZ-DTX and ABI-DTX groups, respectively. After DTX, 18 patients received cabazitaxel, 11 received crossover ABI or ENZ, 8 received estradiol, 4 received radium-223, 1 received flutamide, and 1 received dexamethasone. The investigators observed that PCSS from DTX initiation was significantly prolonged among the subset of patients who received subsequent androgen receptor signaling inhibitors (ARSIs; median, 21.6 months) relative to those who did not (median, 13.8 months; P =.0157) and among the subset of patients who received crossover ABI or ENZ (median, 25.3 months) relative to those who did not (median, 13.8 months; P =.0481). The rates of any grade adverse events were 65% and 57% and grade 3 or higher adverse events were 0% and 10% among ENZ-DTX and ABI-DTX recipients, respectively. The major limitation of this analysis was the small sample sizes, especially among subsequent treatment groups. The study investigators concluded, “The ENABLE study for PCa compared the efficacy of ENZ-DTX and ABI-DTX treatment sequences. Both groups demonstrated similar efficacy in terms of OS and PCSS. The use of additional ARSIs after ARSI-DTX sequential therapy may represent a potential treatment option, as prolonged PCSS from the initiation of DTX was observed.” Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. References: Kamiyama M, Izumi K, Mitxui T, et al. Sequential enzalutamide-docetaxel versus abiraterone-docetaxel therapy in castration-resistant prostate cancer: a subanalysis of the ENABLE study. Int J Urol. 2026;33(8):e70599. doi:10.1111/iju.70599