ALK 阳性晚期非小细胞肺癌患者中克唑替尼与化疗的颅内疗效：PROFILE 1014 研究结果。
Intracranial Efficacy of Crizotinib Versus Chemotherapy in Patients With Advanced ALK-Positive Non-Small-Cell Lung Cancer: Results From PROFILE 1014.
机构信息
Benjamin J. Solomon, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Federico Cappuzzo, Istituto Toscano Tumori, Livorno; Jolanda Paolini, Jennifer Tursi, and Tiziana Usari, Pfizer Oncology, Milan, Italy; Enriqueta Felip, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Barcelona, Spain; Fiona H. Blackhall, The Christie Hospital and Institute of Cancer Sciences, Manchester University, Manchester, United Kingdom; Daniel B. Costa, Beth Israel Deaconess Center, Boston, MA; Tarek Mekhail, Florida Hospital Cancer Institute, Orlando, FL; Keith D. Wilner and Paulina Selaru, Pfizer Oncology, La Jolla, CA; Dong-Wan Kim, Seoul National University Hospital, Seoul, South Korea; Kazuhiko Nakagawa, Kinki University, Osaka, Japan; Yi-Long Wu, Guangdong Lung Cancer Institute, Guangzhou, China; and Tony S.K. Mok, State Key Laboratory of South China, Hong Kong Cancer Institute, The Chinese University of Hong Kong, Shatin, China.
出版信息
J Clin Oncol. 2016 Aug 20;34(24):2858-65. doi: 10.1200/JCO.2015.63.5888. Epub 2016 Mar 28.
PURPOSE
Intracranial efficacy of first-line crizotinib versus chemotherapy was compared prospectively in the phase III PROFILE 1014 study in ALK-positive non-small-cell lung cancer.
PATIENTS AND METHODS
Patients were randomly assigned to receive crizotinib (250 mg twice daily; n = 172) or chemotherapy (pemetrexed 500 mg/m(2) plus cisplatin 75 mg/m(2) or carboplatin at area under the curve 5 to 6, every 3 weeks for ≤ six cycles; n = 171). Patients with stable treated brain metastases (tBM) were eligible. Intracranial efficacy was assessed at baseline and every 6 or 12 weeks in patients with or without known brain metastases (BM), respectively; intracranial time to tumor progression (IC-TTP; per protocol) and intracranial disease control rate (IC-DCR; post hoc) were measured. The intent-to-treat population was also assessed.
RESULTS
Of 343 patients in the intent-to-treat population, 23% had tBM at baseline. A nonsignificant IC-TTP improvement was observed with crizotinib in the intent-to-treat population (hazard ratio [HR], 0.60; P = .069), patients with tBM (HR, 0.45; P = .063), and patients without BM (HR, 0.69; P = .323). Among patients with tBM, IC-DCR was significantly higher with crizotinib versus chemotherapy at 12 weeks (85% v 45%, respectively; P < .001) and 24 weeks (56% v 25%, respectively; P = .006). Progression-free survival was significantly longer with crizotinib versus chemotherapy in both subgroups (tBM present: HR, 0.40; P < .001; median, 9.0 v 4.0 months, respectively; BM absent: HR, 0.51; P < .001; median, 11.1 v 7.2 months, respectively) and in the intent-to-treat population (HR, 0.45; P < .001; median, 10.9 v 7.0 months, respectively).
CONCLUSION
Compared with chemotherapy, crizotinib demonstrated a significantly higher IC-DCR in patients with tBM. Improvements in IC-TTP were not statistically significant in patients with or without tBM, although sensitivity to detect treatment differences in or between the two subgroups was low.
目的
在 III 期 PROFILE 1014 研究中，ALK 阳性非小细胞肺癌患者一线克唑替尼与化疗的颅内疗效进行了前瞻性比较。
方法
患者随机接受克唑替尼（250 mg，每日 2 次；n = 172）或化疗（培美曲塞 500 mg/m2+顺铂 75 mg/m2或卡铂 AUC 5-6，每 3 周 1 次，最多 6 个周期；n = 171）。有稳定治疗脑转移（tBM）的患者符合条件。有或无已知脑转移（BM）的患者分别在基线和每 6 或 12 周评估颅内疗效；根据方案测量颅内肿瘤进展时间（IC-TTP）和颅内疾病控制率（IC-DCR）。还评估了意向治疗人群。
结果
意向治疗人群中 343 例患者中，23%在基线时患有 tBM。意向治疗人群中，克唑替尼治疗组观察到 IC-TTP 有非显著改善（风险比 [HR]，0.60；P =.069），tBM 患者（HR，0.45；P =.063）和无 BM 患者（HR，0.69；P =.323）。在 tBM 患者中，12 周（分别为 85%和 45%；P <.001）和 24 周（分别为 56%和 25%；P =.006）时，克唑替尼的 IC-DCR 显著高于化疗。在两个亚组（tBM 存在：HR，0.40；P <.001；中位数，9.0 v 4.0 个月，分别；BM 不存在：HR，0.51；P <.001；中位数，11.1 v 7.2 个月，分别）和意向治疗人群（HR，0.45；P <.001；中位数，10.9 v 7.0 个月，分别）中，克唑替尼的无进展生存期明显长于化疗。
结论
与化疗相比，克唑替尼治疗 tBM 患者的 IC-DCR 显著更高。尽管在这两个亚组中或之间检测治疗差异的敏感性较低，但 tBM 患者和无 tBM 患者的 IC-TTP 改善均无统计学意义。
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