Rodríguez Antolín Alfredo, Romero Otero Javier, Duarte Ojeda José, García González Lucía, Sopeña Sutil Raquel, González Padilla Daniel, García Rojo Esther, Justo Quintas Juan, Miñana López Bernardino
Servicio de Urología. Hospital Universitario 12 de Octubre. Madrid. España.
Arch Esp Urol. 2018 Mar;71(3):267-275.
The treatment of metastatic prostate cancer has remained unchanged for more than 70 years, based on androgen deprivation therapy (ADT). In 2015, following the CHAARTED and STAMPEDE trials, it was established that the addition of 6 cycles of docetaxel to ADT was associated with significantly increased survival. In June 2017, the LATITUDE trial and the G arm of the STAMPEDE trial showed that the addition of Abiraterone with Prednisone (5 mg/day) to ADT was also associated with a significant increase in survival in metastatic patients. The present study analyzes these two trials.
LATITUDE demonstrated a 38% reduction in the risk of death (HR=0.62, 95% CI, 0.61-0.76) in almost all sub-groups. Risk reduction for radiological progression was 53% (HR=0.47, 95% CI 0.39-0.55). Secondary objectives such as prostate specific antigen progression, time to chemotherapy or a new skeletal event are also significantly delayed. STAMPEDE also showed that the combination of Abiraterone and Prednisone is associated with a 37% increase in survival (HR=0.63, 95% CI, 0.52- 0.76, p<0.001) in metastatic patients, but not in nonmetastatic patients. Progression-free survival was greatly improved in this arm (HR=0.29, 95% CI 0.25-0.34, p<0.001). The side effects reported show the known pattern of mineral corticosteroid excess with increased blood pressure, hypokalemia, and of liver enzymes elevation.
The indirect comparison of docetaxel and abiraterone studies confirms that both populations and results are comparable. Two comparative indirect metanalysis (>6000 patients) gave marginal superiority to abiraterone. In favor of abiraterone we have that it is an oral, comfortable medication with a good tolerance profile and side effects that are easy to manage, useful in patients who are old and fragile, in whom chemotherapy may not be indicated; the downsides are prolonged exposure to the drug and its current price. Future trials, currently in progress, will determine the ideal patient profile, or a potential association of both therapies.
基于雄激素剥夺疗法(ADT),转移性前列腺癌的治疗70多年来一直未变。2015年,在CHAARTED和STAMPEDE试验之后,确定在ADT基础上加用6个周期的多西他赛可显著提高生存率。2017年6月,LATITUDE试验和STAMPEDE试验的G组表明,在ADT基础上加用阿比特龙与泼尼松(5毫克/天)也可显著提高转移性患者的生存率。本研究对这两项试验进行分析。
LATITUDE试验表明,几乎所有亚组的死亡风险降低了38%(风险比[HR]=0.62,95%置信区间[CI],0.61 - 0.76)。影像学进展的风险降低了53%(HR=0.47,95% CI 0.39 - 0.55)。前列腺特异性抗原进展、化疗时间或新的骨骼事件等次要目标也显著延迟。STAMPEDE试验也表明,阿比特龙与泼尼松联合使用可使转移性患者的生存率提高37%(HR=0.63, 95% CI, 0.52 - 0.76, p<0.001),但对非转移性患者无效。该组的无进展生存期有显著改善(HR=0.29, 95% CI 0.25 - 0.34, p<0.001)。报告的副作用显示出已知的盐皮质激素过量模式,即血压升高、低钾血症和肝酶升高。
多西他赛和阿比特龙研究的间接比较证实,研究人群和结果具有可比性。两项比较性间接荟萃分析(>6000例患者)显示阿比特龙略占优势。阿比特龙有利的方面在于它是一种口服、使用方便的药物,耐受性良好,副作用易于控制,适用于年老体弱、可能不适合化疗的患者;不利的方面是药物暴露时间长和目前的价格。目前正在进行的未来试验将确定理想的患者类型或两种疗法的潜在联合应用。