XL184在II期临床实验中对上皮性卵巢癌显示出疗效
本帖最后由 seacat 于 2014-1-22 18:38 编辑Abstract:
Background: Cabozantinib (Cabo) is an oral, potent inhibitor of MET and VEGFR2. MET over-expression has been observed in advanced ovarian cancer (OC). Anti-VEGF pathway agents have shown clinical benefit in pts w/ OC. Simultaneous targeting of the MET and VEGF signaling pathways with Cabo may therefore be a promising treatment strategy.
Methods:
Epithelial OC pts with progressive measurable disease (mRECIST) received Cabo at 100 mg qd PO over a 12 wk Lead-in stage. Up to 2 prior regimens are allowed for platinum-resistant (R), and up to 3 prior regimens for platinum-sensitive (S) pts.
Tumor response was assessed every 6 wks. Treatment ≥ wk 12 was based on response: pts with PR continued open-label Cabo, pts with SD were randomized to Cabo vs placebo, and pts with PD discontinued.
Primary endpoint was ORR per mRECIST in the Lead-in stage, and progression free survival (PFS) in the randomized period. Accrual in any cohort could be halted for either high rates of ORR or PD.
Results:
Accrual was halted at 68 pts based on an observed high rate of clinical activity. The median number of prior systemic treatments was 2. Most common related AEs ≥Grade 3 were hand-foot syndrome (10%), diarrhea (8%) and fatigue (4%). Dose reductions and permanent discontinuations for AEs occurred in 43% and 10% of pts, respectively. Of 51 pts evaluable for mRECIST RR at 12 wks, 28 are R, 17 are S, and 6 have unknown status. mRECIST RR at 12 wks: overall = 12/51(24%), R = 5/28(18%); S= 5/17(29%). Five additional PRs await confirmation.
The overall DCR (PR+SD) at wk 12 is 58% (30/51). After a median f/u of 4 mos (range: 1 to 11 mos), the median duration of response and median PFS have not been reached. CA125 responses (assessed by GCIG criteria) in 40 pts with ≥1 post-baseline result: 7/40 (18%). Median maximum increase in hemoglobin (Hb) in anemic pts (Hb < 11 g/dL) was 1.9 g/dL (N=8 in pts w/ ≥ 6 wk f/u; range, 1.1-3.2 g/dL). All maximum Hb changes occurred w/in the first 12 wks. Randomization in this cohort was halted & pts unblinded due to observed efficacy.
Conclusions: Cabo exhibits clinical activity in ovarian cancer pts with advanced disease, regardless of prior platinum status, as reflected by high rates of response.
我的评论：12周疾病控制率（PR+SD）58%，客观反应率（PR）24%，无论铂类是否敏感都有较高反映率，铂类耐药组反应率5/28（18%），铂类敏感组反应率5/17（29%）。
主要副作用是手足综合症、疲乏，40%的病人要减量，10%停药。
实验剂量是100mg/d，亚洲人估计要减量，单药80mg/d较为稳妥。
请教海猫一般184对骨转有效率高。对肺部肿瘤控制效果怎么样，肺癌骨转单用184可以吗？ 珈蓝夜听雪 发表于 2014-1-27 22:10
请教海猫一般184对骨转有效率高。对肺部肿瘤控制效果怎么样，肺癌骨转单用184可以吗？
只要分子类型适合管你肺部，脑部，通通有效。 seacat 发表于 2014-1-27 23:47
只要分子类型适合管你肺部，脑部，通通有效。
理解了，谢谢海猫 http://www.yuaigongwu.com/thread-10991-1-1.html，海猫，我家用184单药有效，下一步该如何走呢？求建议？谢谢海猫{:soso_e163:} 学习了，多谢楼主 了解了，多谢 jack_7777 发表于 2014-9-14 21:50
海猫 您好,
看了坛内很多网友帖子, 对赠药都看的很淡, 好像诱惑力不大, ( 想想也对, &# ...
可以换药，换特罗凯。
只要药物有效，就不会新增转移。至于预防XX，不用想太多，有这么好的办法，为啥不直接预防得肺癌？