Department of Oncology, University of Turin, AOU San Luigi, Orbassano, Italy.
San Camillo Forlanini Hospital, UOSD Pneumologia Oncologica, Roma, Italy.
Lung Cancer. 2019 Aug;134:210-217. doi: 10.1016/j.lungcan.2019.06.028. Epub 2019 Jun 27.
Despite the scant docetaxel's tolerability, second-line association with nintedanib still represents a standard-of-care for non-squamous non-small cell lung cancer (nsNSCLC), giving to rapidly-progressing patients the greatest survival advantage. The SENECA trial is a phase IIb, open-label, study evaluating whether nintedanib/docetaxel can be equally effective and safe regardless docetaxel schedule.
Recurrent nsNSCLC patients were stratified into cohort 1 and 2, according to relapse-time (within or over 3 months) from end of first-line chemotherapy. They were treated with docetaxel (T1: 33 mg/mq on days 1 and 8 in a 21-days cycle; T2: 75 mg/mq q3wks) plus nintedanib, allowing maintenance in case of disease-control. Primary endpoint was progression-free survival (PFS) by investigator's assessment; secondary endpoints: overall survival (OS), safety and quality-of-life.
Between January 2016-April 2018, 212 patients were evaluated: 30 resulted screening-failures, 12 were excluded for lack of compliance. According to investigator's choice, 85 patients received T1 docetaxel and 85 T2; 138 (81.2%) were stratified in C1, 32 (18.8%) in C2, with a median relapse-time of 0.54 and 9.29 months, respectively. Baseline characteristics were balanced between groups. After 35.5 months follow-up, no survival differences appear between cohorts and treatments; toxicity seems to be slightly higher in T2, especially for chemotherapy-related events. Perception of quality-of-life remains stable and docetaxel schedule doesn't modify patients' load.
The SENECA trial confirms efficacy of second-line nintedanib/docetaxel for nsNSCLC, regardless time of recurrence and docetaxel schedule; higher toxicities for q3wks docetaxel, without alterations in quality-of-life, have been described, underling the possibility, adopting the weekly schedule, to maintain efficacy with better tolerability.
尽管多西他赛的耐受性较差，但二线联合尼达尼布仍是非鳞状非小细胞肺癌（nsNSCLC）的标准治疗方法，为快速进展的患者带来最大的生存优势。SENECA 试验是一项 IIb 期、开放标签的研究，旨在评估尼达尼布/多西他赛无论多西他赛方案如何，是否同样有效和安全。
根据一线化疗结束后复发时间（3 个月内或超过 3 个月），将复发性 nsNSCLC 患者分为队列 1 和队列 2。他们接受多西他赛（T1：第 1 天和第 8 天每 21 天周期 33mg/mq；T2：每 3 周 75mg/mq）加尼达尼布治疗，如果疾病得到控制，则允许维持治疗。主要终点是研究者评估的无进展生存期（PFS）；次要终点：总生存期（OS）、安全性和生活质量。
2016 年 1 月至 2018 年 4 月，共评估了 212 名患者：30 名因筛选失败，12 名因不遵医嘱而被排除。根据研究者的选择，85 名患者接受 T1 多西他赛，85 名患者接受 T2 多西他赛；138 名（81.2%）患者被分层为 C1，32 名（18.8%）患者被分层为 C2，中位复发时间分别为 0.54 个月和 9.29 个月。两组基线特征平衡。在 35.5 个月的随访后，两组和两种治疗方案之间没有出现生存差异；T2 组的毒性似乎略高，尤其是与化疗相关的事件。生活质量的感知仍然稳定，多西他赛方案不会改变患者的负担。
SENECA 试验证实了二线尼达尼布/多西他赛治疗 nsNSCLC 的疗效，无论复发时间和多西他赛方案如何；q3wks 多西他赛毒性更高，但生活质量没有改变，这表明采用每周方案可以在提高耐受性的同时保持疗效。
