新药Cabozantinib为肺癌、肝癌、骨转移癌治疗带来了新希望

bkcui 发表于 2011-5-26 11:59

                               
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XL184  是BMS 公司的，目前已到了3期临床了，但是没有肝癌。                     ...

BMS这个值得关注的，已经3期了。

Cabozantinib可控制多种肿瘤和骨转移
2011年5月25日消息 - Cabozantinib(XL184)的Ⅱ期临床试验结果显示，该试验新药对多种晚期癌症具有较高的疾病控制率，并且可缩小甚至消除骨转移病灶。美国亚利桑那州Pinnacle肿瘤血液医院的Michael S. Gordon博士将在6月份召开的美国临床肿瘤学会(ASCO)年会上报告上述研究结果。

该项试验设计为随机终止试验(RDT)，纳入398例进展性可测量性癌症患者，其中39%的患者在入组时已发生骨转移。在开放性研究阶段，所有患者每天服用100 mg 受试药物，共12周。病情进展(增长≥20%)患者退出试验，部分应答患者(缩小≥30%)继续服药，病情稳定患者随机分组接受cabozantinib或安慰剂治疗。

结果显示，cabozantinib对13种肿瘤中的12种具有抗肿瘤活性，并且骨扫描结果显著改善。虽然总应答率仅为9%，但cabozantinib单药治疗12周后，肝癌、前列腺癌和卵巢癌患者的疾病稳定率分别可达76%、71%和58%，黑色素瘤、乳腺癌和非小细胞肺癌的疾病控制率分别为45%、45%和40%。

令人惊讶的是，在68例骨转移患者中，59例骨转移缩小或消除。包括乳腺癌、前列腺癌和黑色素瘤在内的患者，骨扫描显示转移病灶部分或完全消失，并且在治疗6周后即可得到改善。

这是ASCO网站发布的英文摘要：

Activity of cabozantinib (XL184) in soft tissue and bone: Results of a phase II randomized discontinuation trial (RDT) in patients (pts) with advanced solid tumors.

Abstract:

Background: Cabozantinib (Cabo) is an oral, potent inhibitor of MET and VEGFR2. An RDT evaluated clinical efficacy and safety in 9 tumor types: breast (B), gastric/GEJ (G), non-small cell lung (NS), ovarian (O), pancreatic (PA), castration-resistant prostate (P), small cell lung (S), hepatocellular (H), and melanoma (M). Indications were selected based on the role of MET and VEGFR2 in tumor biology. Methods: All eligible pts had progressive measurable disease ± bone metastasis (mets). Pts received Cabo at 100 mg qd over a 12 wk lead-in stage. Tumor response (mRECIST) assessed q6 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 in the lead-in stage. Accrual in any cohort could be halted for either high rates of ORR or PD. Results: 398/483 enrolled pts were evaluable for the lead-in stage. 154/398 (39%) had bone mets at baseline (68 with bone scan f/u). Median # prior regimens was 2. Most common related AEs grade ≥ 3: fatigue (9%), hand-foot syndrome (8%), and HTN (5%). Dose reductions and permanent discontinuations for AEs occurred in 41% and 12% of pts, respectively. Soft tissue effects: ORR at wk 12: overall = 34/398 (9%); O 12/51 (24%), H 4/29 (14%), P 5/100 (5%), NS 6/60 (10%), B 2/20 (10%), S 1/21 (5%), M 4/76 (5%). 12 additional PRs await confirmation. 226/328 (69%) with ≥1 post-baseline scan had tumor regression. Highest DCR (PR + SD) at wk 12: H (76%), P (71%), and O (58%). Bone effects: 59/68 pts (P, B, and M) with bone mets and ≥1 post-baseline bone scan had partial or complete bone scan resolution, often with symptom improvement seen by wk 6. Osteoclast effects were observed across tumor types: 66/121 (55%) pts ± bone mets had declines of ≥50% in plasma C-telopeptide. Decreased serum tALP seen in P. Median max rise in hemoglobin in anemic pts (Hb < 11 g/dL) = 2.3 g/dL. All max Hb changes w/in first 12 wks. Randomization in cohorts P and O was halted and pts unblinded due to observed efficacy. Conclusions: Cabo is broadly active with cPRs in 8/9 indications, with high DCRs in H, P, and O. Complete or partial resolution of bone scan lesions was observed in 3 tumor types.

把结果整理一下，好看一点：

Most common related AEs grade ≥ 3: fatigue (9%),
                                                        hand-foot syndrome (8%),
                                                         HTN (5%).
Dose reductions and permanent discontinuations for AEs occurred in 41% and 12% of pts, rSoft tissue effects:
ORR at wk 12: overall = 34/398 (9%);
                                       O 12/51 (24%),
                                       H 4/29 (14%),
                                       P 5/100 (5%),
                                      NS 6/60 (10%),
                                      B 2/20 (10%),
                                      S 1/21 (5%),
                                       M 4/76 (5%).
12 additional PRs await confirmation. 226/328 (69%) with ≥1 post-baseline scan had tumor regression.
Highest DCR (PR + SD) at wk 12: H (76%), P (71%), and O (58%).
Bone effects: 59/68 pts (P, B, and M) with bone mets and ≥1 post-baseline bone scan had partial or complete bone scan resolution,
often with symptom improvement seen by wk 6. Osteoclast effects were observed across tumor types: 66/121 (55%) pts ± bone mets had declines of ≥50% in plasma C-telopeptide.
Decreased serum tALP seen in P.
Median max rise in hemoglobin in anemic pts (Hb < 11 g/dL) = 2.3 g/dL. All max Hb changes w/in first 12 wks.
Randomization in cohorts P and O was halted and pts unblinded due to observed efficacy

有这么好的二期结果的药物，pubmed上还少见。

能够逆转骨转，非常罕有。

憨豆精神 发表于 2011-5-29 11:15

                               
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能够逆转骨转，非常罕有。

这一点是属于太强大了，很期待这个药物。