早有证据阿西替尼效果比不上阿瓦斯丁，希望探讨原因

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本帖最后由 dgarden 于 2013-7-21 22:27 编辑

阿西替尼在非小细胞肺癌实验中作为辅助药物失败

主要内容是阿西替尼的中位无进展生存期为5.7月，阿瓦斯丁为6.1月；总生存期阿西替尼为10.6月，阿瓦斯丁为13.3月。

VIENNA – A once-promising small molecule did not improve treatment efficacy when added to standard platinum-based therapy for advanced non-small cell lung cancer (NSCLC), researchers reported.

A phase II trial of the tyrosine kinase inhibitor axitinib (Inlyta), combined with platinum-based doublet chemotherapy, was stopped early because of disappointing efficacy results, according to Chris Twelves, MD, of St James' University Hospital in Leeds, England, and colleagues.

In addition, the treatment was associated with a higher rate of adverse events leading to dose reductions and temporary halts to therapy compared with bevacizumab, when each one was added to platinum-based therapy, Twelves told a poster session at the annual meeting of the European Society for Molecular Oncology here.

The drug, approved for advanced renal cell carcinoma, blocks receptors for the vascular endothelial growth factor (VEGF), Twelves noted.

The monoclonal VEGF antibody bevacizumab (Avastin) is known to improve outcomes in NSCLC when added to platinum-based chemotherapy, and an early study showed axitinib as a single agent was active against advanced disease.

To study the issue in more detail, Twelves and colleagues enrolled 118 treatment-naive patients with advanced or recurrent nonsquamous NSCLC for a randomized open-label trial.

All patients were treated with a standard regimen of paclitaxel (Taxol) and carboplatin (Paraplatin), combined with either bevacizumab or axitinib.

The primary endpoint of the study was the rate of progression-free survival, while secondary endpoints included overall survival, objective response rates, the length of response, safety, and patient-reported outcomes.

But the axitinib arm of the study was stopped in April 2010 after a preliminary analysis showed numerically inferior progression-free and overall survival, as well as a higher rate of adverse events, compared with the bevacizumab arm, Twelves reported.

The final results showed no significant efficacy difference between the two arms, the researchers found:

Median progression-free survival among axitinib patients was 5.7 months, compared with 6.1 months for bevacizumab, yielding a nonsignificant hazard ratio of 1.093 in favor of bevacizumab.
Median overall survival for axitinib was 10.6 months, compared with 13.3 for bevacizumab, leading to a nonsignificant hazard ratio of 1.117 in favor of bevacizumab.
The objective response rates were 29.3% and 43.3% for axitinib and bevacizumab, respectively.
The median duration of response was 4.4 months for axitinib and 7 months for bevacizumab.

Also, axitinib was harder to tolerate than the older drug, Twelves and colleagues found.

Many of the treatment-emergent adverse events were higher in the axitinib arm, including diarrhea (47% versus 34%), decreased appetite (43% versus 22%), nausea (36% versus 32%), and neutropenia (31% versus 27%).

On the other hand, rates of hypertension were similar between arms, at 43% for axitinib and 42% for bevacizumab. Axitinib patients also showed less hair loss (36% versus 46%) and fatigue (34% versus 39%).

More axitinib patients stopped therapy because of adverse events -- 41%, compared with 31% in the bevacizumab arm.

原文链接 http://www.medpagetoday.com/MeetingCoverage/ESMO/35172