Autio Karen A, Antonarakis Emmanuel S, Mayer Tina M, Shevrin Daniel H, Stein Mark N, Vaishampayan Ulka N, Morris Michael J, Slovin Susan F, Heath Elisabeth I, Tagawa Scott T, Rathkopf Dana E, Milowsky Matthew I, Harrison Michael R, Beer Tomasz M, Balar Arjun V, Armstrong Andrew J, George Daniel J, Paller Channing J, Apollo Arlyn, Danila Daniel C, Graff Julie N, Nordquist Luke, Dayan Cohn Erica S, Tse Kin, Schreiber Nicole A, Heller Glenn, Scher Howard I
Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Weill Cornell Medical College, New York, NY, USA.
Eur Urol Open Sci. 2021 Nov 17;34:70-78. doi: 10.1016/j.euros.2021.09.015. eCollection 2021 Dec.
Phase 2 trial endpoints that can be utilized in high-risk biochemical recurrence (BCR) after prostatectomy as a way of more rapidly identifying treatments for phase 3 trials are urgently needed. The efficacy of abiraterone acetate plus prednisone (AAP) in BCR is unknown.
To compare the rates of complete biochemical responses after testosterone recovery after 8 mo of AAP and degarelix, a gonadotropin-releasing hormone antagonist, alone or in combination.
Patients with BCR (prostate-specific antigen [PSA] ≥1.0 ng/ml, PSA doubling time ≤9 mo, no metastases on standard imaging, and testosterone ≥150 ng/dl) after prostatectomy (with or without prior radiotherapy) were included in this study.
Patients were randomized to AAP (arm 1), AAP with degarelix (arm 2), or degarelix (arm 3) for 8 mo, and monitored for 18 mo.
The primary endpoint was undetectable PSA with testosterone >150 ng/dl at 18 mo. Secondary endpoints were undetectable PSA at 8 mo and time to testosterone recovery.
For the 122 patients enrolled, no difference was found between treatments for the primary endpoint (arm 1: 5.1% [95% confidence interval {CI}: 1-17%], arm 2: 17.1% [95% CI: 7-32%], arm 3: 11.9% [95% CI: 4-26%]; arm 1 vs 2, = 0.93; arm 2 vs 3, = 0.36). AAP therapy showed the shortest median time to testosterone recovery (36.0 wk [95% CI: 35.9-36.1]) relative to degarelix (52.9 wk [95% CI: 49.0-56.0], < 0.001). Rates of undetectable PSA at 8 mo differed between AAP with degarelix and degarelix alone ( = 0.04), but not between AAP alone and degarelix alone ( = 0.12). Limitations of this study include a lack of long-term follow-up.
Rates of undetectable PSA levels with testosterone recovery were similar between arms, suggesting that increased androgen suppression with AAP and androgen deprivation therapy (ADT) is unlikely to eradicate recurrent disease compared with ADT alone.
We evaluated the use of abiraterone acetate plus prednisone (AAP) and androgen deprivation therapy (ADT), AAP alone, or ADT alone in men with biochemically recurrent, nonmetastatic prostate cancer. While more men who received the combination had an undetectable prostate-specific antigen (PSA) level at 8 mo on treatment, once men came off treatment and testosterone level rose, there was no difference in the rates of undetectable PSA levels. This suggests that the combination is not able to eradicate disease any better than ADT alone.
迫切需要可用于前列腺切除术后高风险生化复发（BCR）的2期试验终点，以便更快速地确定3期试验的治疗方法。醋酸阿比特龙加泼尼松（AAP）在BCR中的疗效尚不清楚。
比较AAP和促性腺激素释放激素拮抗剂地加瑞克单独或联合使用8个月后睾酮恢复后完全生化反应的发生率。
设计、设置和参与者：本研究纳入了前列腺切除术后（有或无既往放疗史）出现BCR（前列腺特异性抗原[PSA]≥1.0 ng/ml，PSA加倍时间≤9个月，标准影像学检查无转移，睾酮≥150 ng/dl）的患者。
患者被随机分为AAP组（第1组）、AAP联合地加瑞克组（第2组）或地加瑞克组（第3组），治疗8个月，并监测18个月。
主要终点是在18个月时PSA不可检测且睾酮>150 ng/dl。次要终点是8个月时PSA不可检测以及睾酮恢复时间。
对于纳入的122例患者，各治疗组在主要终点方面未发现差异（第1组：5.1%[95%置信区间{CI}：1-17%]，第2组：17.1%[95% CI：7-32%]，第3组：11.9%[95% CI：4-26%]；第1组与第2组比较，P = 0.93；第2组与第3组比较，P = 0.36）。与地加瑞克相比，AAP治疗的睾酮恢复中位时间最短（36.0周[95% CI：35.9-36.1]）（地加瑞克为52.9周[95% CI：49.0-56.0]，P < 0.001）。AAP联合地加瑞克组与单独使用地加瑞克组在8个月时PSA不可检测的发生率存在差异（P = 0.04），但单独使用AAP组与单独使用地加瑞克组之间无差异（P = 0.12）。本研究的局限性包括缺乏长期随访。
各治疗组中睾酮恢复时PSA不可检测的发生率相似，这表明与单独使用雄激素剥夺疗法（ADT）相比，AAP联合ADT增加雄激素抑制不太可能根除复发性疾病。
我们评估了醋酸阿比特龙加泼尼松（AAP）和雄激素剥夺疗法（ADT）、单独使用AAP或单独使用ADT在生化复发、非转移性前列腺癌男性中的应用。虽然更多接受联合治疗的男性在治疗8个月时前列腺特异性抗原（PSA）水平不可检测，但一旦男性停止治疗且睾酮水平升高，PSA不可检测的发生率并无差异。这表明联合治疗并不比单独使用ADT更能根除疾病。
