Medical Oncology Unit 2, Medical Oncology Department, Fondazione IRCCS Istituto Nazione dei Tumori, Milan, Italy.
Radiology Department, Fondazione IRCCS Istituto Nazione dei Tumori, Milan, Italy.
Cancer. 2018 Oct 15;124(20):4056-4063. doi: 10.1002/cncr.31685. Epub 2018 Sep 14.
We present the results of an academic phase 2 study on imatinib plus everolimus in patients who have progressive advanced chordoma.
In January 2011, 43 adult chordoma patients were enrolled in the study and received imatinib 400 mg/day and everolimus 2.5 mg/day until progression or limiting toxicity. Eligible patients had progressed in the 6 months before study entry. PDGFRB, S6, and 4EBP1 expression and phosphorylation were evaluated by way of immunohistochemistry and/or western blotting. The primary endpoint was the overall response rate (ORR) according to Choi criteria. Secondary endpoints were RECIST 1.1 response, progression-free survival (PFS), overall survival (OS), correlation between S6/4EBP1 phosphorylation and response.
Thirteen of 43 patients were pretreated with imatinib. Among 40 of the 43 patients who were evaluable by Choi criteria, the best responses were 9 with partial response (ORR, 20.9%), 24 with stable disease (SD) (ORR, 55.8%), and 7 with progressive disease (ORR, 16.3%). Forty-two patients were evaluable by RECIST criteria, with 1 partial response (ORR, 2.3%), 37 stable disease (ORR, 86%), and 4 progressive disease (ORR, 9.3%). The median PFS according to Choi criteria was 11.5 months (range, 4.6-17.6 months), and 58.8% and 48.1% of patients were progression-free at 9 and 12 months, respectively. The median PFS by RECIST criteria was 14 months; the median OS was 47.1 months. When assessable, S6/4EBP1 was phosphorylated in a high and moderate/low proportion of tumor cells in responsive and nonresponsive patients, respectively. Toxicity caused a temporary and definitive treatment discontinuation in 60.5% and 30.2% of patients, respectively.
Imatinib plus everolimus showed a limited activity in progressing advanced chordoma. Interestingly, the amount of tumor cells activated for mammalian target of rapamycin effectors correlated with the response. Toxicity was not negligible.
我们报告了一项关于伊马替尼联合依维莫司治疗进展性晚期脊索瘤患者的学术 2 期研究结果。
2011 年 1 月，43 例成人脊索瘤患者入组该研究，接受伊马替尼 400mg/天和依维莫司 2.5mg/天治疗，直至疾病进展或出现不可耐受的毒性。符合条件的患者在研究入组前 6 个月内疾病进展。通过免疫组化和/或 Western blot 评估 PDGFRB、S6 和 4EBP1 的表达和磷酸化。主要终点为 Choi 标准的总缓解率（ORR）。次要终点为 RECIST 1.1 缓解率、无进展生存期（PFS）、总生存期（OS）、S6/4EBP1 磷酸化与缓解的相关性。
43 例患者中有 13 例曾接受伊马替尼治疗。43 例可按 Choi 标准评价的患者中，最佳缓解为 9 例部分缓解（ORR，20.9%）、24 例疾病稳定（SD）（ORR，55.8%）和 7 例疾病进展（ORR，16.3%）。42 例可按 RECIST 标准评价，1 例部分缓解（ORR，2.3%）、37 例疾病稳定（ORR，86%）和 4 例疾病进展（ORR，9.3%）。按 Choi 标准的中位 PFS 为 11.5 个月（范围，4.6-17.6 个月），9 个月和 12 个月时无进展生存率分别为 58.8%和 48.1%。按 RECIST 标准的中位 PFS 为 14 个月，中位 OS 为 47.1 个月。在可评估的情况下，在有反应和无反应患者中，肿瘤细胞中 S6/4EBP1 磷酸化的比例分别为高和中/低。毒性导致 60.5%和 30.2%的患者暂时和永久停止治疗。
伊马替尼联合依维莫司在进展性晚期脊索瘤中表现出有限的活性。有趣的是，肿瘤细胞中被哺乳动物雷帕霉素效应器激活的比例与缓解相关。毒性不容忽视。
