Oh William K, Cheng Wendy Y, Miao Raymond, Vekeman Francis, Gauthier-Loiselle Marjolaine, Duh Mei Sheng, Drea Edward, Szatrowski Ted P
Division of Hematology and Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
Analysis Group, Inc., Boston, MA.
Urol Oncol. 2018 Nov;36(11):500.e1-500.e9. doi: 10.1016/j.urolonc.2018.08.002. Epub 2018 Sep 7.
This retrospective observational study assessed if second-line chemotherapy vs. androgen receptor-targeted agents (ARTAs; abiraterone/enzalutamide) is associated with improved outcomes in metastatic castration-resistant prostate cancer (mCRCaP) patients who experience early progression on first-line ARTAs in a US community setting.
Patients with mCRCaP (n = 345) who progressed ≤ 12 months after first-line ARTA and received second-line chemotherapy (docetaxel/cabazitaxel; n = 147) or ARTA (n = 198) between May 2011 and October 2014 were identified. Overall survival (OS), prostate-specific antigen (PSA) response and progression, and clinical response were compared for second-line chemotherapy vs. ARTA, using one-sided tests from second-line therapy initiation. Multivariate analyses were adjusted for: year, age, metastases, opioid use, Eastern Cooperative Oncology Group performance score, PSA, hemoglobin, alkaline phosphatase, lactate dehydrogenase (LDH), and albumin levels.
Patients receiving second-line chemotherapy vs. ARTA were younger (median: 74 vs. 79 years) and had a poorer prognosis in terms of PSA, LDH, alkaline phosphatase, albumin and hemoglobin levels, opioid use, and Halabi risk score (P < 0.05). Response rates were higher for chemotherapy vs. ARTA (PSA: adjusted odds ratio = 2.27, P = 0.005; clinical: adjusted odds ratio = 1.78; P = 0.020) and time to PSA progression was longer (adjusted hazard ratio [aHR] = 0.66; P = 0.010). A trend favored chemotherapy vs. ARTA for OS (aHR = 0.81, P = 0.148). Among patients with poor prognostic features, those receiving chemotherapy had significantly improved OS (Halabi intermediate-/high-risk score: aHR = 0.55, P = 0.009; hemoglobin < 11 g/dl: aHR = 0.41, P = 0.002; LDH > upper limit of normal: aHR = 0.18, P = 0.014; albumin < lower limit of normal: aHR = 0.42, P = 0.020).
Following early progression on first-line ARTA, second-line chemotherapy may be more beneficial in mCRCaP compared with second-line ARTA in patients with a poor prognosis.
这项回顾性观察性研究评估了在美国社区环境中，转移性去势抵抗性前列腺癌（mCRCaP）患者在一线雄激素受体靶向药物（ARTA；阿比特龙/恩杂鲁胺）治疗早期进展后，接受二线化疗与ARTA治疗相比，是否能带来更好的治疗结果。
确定了2011年5月至2014年10月期间，mCRCaP患者（n = 345），这些患者在一线ARTA治疗后≤12个月出现疾病进展，并接受了二线化疗（多西他赛/卡巴他赛；n = 147）或ARTA（n = 198）治疗。从二线治疗开始，采用单侧检验比较二线化疗与ARTA治疗的总生存期（OS）、前列腺特异性抗原（PSA）反应与进展情况以及临床反应。多变量分析对以下因素进行了调整：年份、年龄、转移情况、阿片类药物使用情况、东部肿瘤协作组体能状态评分、PSA、血红蛋白、碱性磷酸酶、乳酸脱氢酶（LDH）和白蛋白水平。
接受二线化疗的患者与接受ARTA治疗的患者相比更年轻（中位年龄：74岁对79岁），在PSA、LDH、碱性磷酸酶、白蛋白和血红蛋白水平、阿片类药物使用情况以及哈拉比风险评分方面预后较差（P < 0.05）。化疗组的反应率高于ARTA组（PSA：调整后的优势比 = 2.27，P = 0.005；临床反应：调整后的优势比 = 1.78；P = 0.020），且PSA进展时间更长（调整后的风险比[aHR] = 0.66；P = 0.010）。OS方面有化疗优于ARTA的趋势（aHR = 0.81，P = 0.148）。在预后特征较差的患者中，接受化疗的患者OS显著改善（哈拉比中/高风险评分：aHR = 0.55，P = 0.009；血红蛋白 < 11 g/dl：aHR = 0.41，P = 0.002；LDH > 正常上限：aHR = 0.18，P = 0.014；白蛋白 < 正常下限：aHR = 0.42，P = 0.020）。
在一线ARTA治疗早期进展后，对于预后较差的mCRCaP患者，二线化疗可能比二线ARTA治疗更有益。
