新药介绍: 第三代EGFR TKI，EGF816-诺华和ASP8273-Astellas

Asp8273副作用更小，效率更高,ORR 78%，值得期待。
有点遗憾是小日本的药，数据不是很可信。{:soso_e101:}

一点想法。到目前为止，好像好没有任何报道关于已有的第三代TKI，9291,1686,4002,是否不交叉耐药？并且，似乎均非不可逆TKI？

而这两新药EGF816和ASP8273都是不可逆TKI。是否比9291,1686,4002要强一些？第二代TKI相比第一代TKI的一大特点也是不可逆。

真心希望这5种第三代TKI都不交叉耐药。交叉耐药的机理是什么？

9291,1686,4002也都是不可逆TKI。
从ALK的第二代，第三代药物来看，可以顺序使用，至少是不完全交叉耐药。
而从9291，4002的实际使用情况看，也可以换用。

希望可以入脑

求新药的用药量，是否需要肠溶胶囊？

老马 发表于 2014-11-22 19:34
Asp8273副作用更小，效率更高,ORR 78%，值得期待。
有点遗憾是小日本的药，数据不是很可信。 ...

HM781-36B 是韩国的，有效率不是很高，而副作用太大，导致用的人比较少。

不知道小日本的药是否能比韩国的好些

顶一下

期待早点出来

In a second presentation looking at new ways of treating non-small cell lung cancer (NSCLC) that has both the EGFR and T790M mutations, researchers tod the 26th EORTC-NCI-AACR1 Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain, that an oral drug called ASP8273 has caused tumour shrinkage in patients in a phase I clinical trial in Japan.

Mutations of the epidermal growth factor (EGFR) occur in about 30-35% of Asian patients with NSCLC (and in 10-15% of Caucasian patients). EGFR inhibitors called tyrosine kinase inhibitors (TKI)2, such as erlotinib, gefitinib and afatinib, can be used to treat EGFR-mutated NSCLC. However, these patients will eventually develop resistance to EGFR TKI therapy, rendering their disease resistant to current treatments. A further mutation called T790M accounts for 60% of this acquired resistance.

ASP8273 is a new drug that inhibits the EGFR mutation and the T790M resistance mutation. Earlier research in mice had shown that it caused NSCLC to disappear completely, and so a phase I clinical trial was started in January 2014 to assess the drug's safety and efficacy in humans.

Twenty-four Japanese patients have enrolled so far to receive one of six levels of doses (25, 50, 100, 200, 400 and 600mg) once a day. A further seven patients have been enrolled into a second group to evaluate doses of 100mg, 200mg and 400mg a day (a dose escalation study), and the researchers are planning to enrol a total of 124 patients. Cancer had progressed in all the patients after prior treatment with EGFR TKI therapy, and most of them had the T790M mutation.

Dr Haruyasu Murakami, of the Shizuoka Cancer Center, Shizuoka, Japan, told the meeting: "Preliminary results from this study show a high overall response rate of 78%, with tumours shrinking in seven out of nine patients who had both the EGFR and T790M mutations. While the number of patients is still small, this response is comparable with two other drugs in development that target EGFR - CO-1689 and AZ-9291 - but ASP8273 has fewer safety concerns than these drugs."

The most common adverse reactions to ASP8273 were mild cases of diarrhoea (in half of the patients), nausea and vomiting (in a third of the patients). There were none of the severe respiratory complications, heart problems and high blood sugar levels that have occurred during the clinical trials of the other two drugs. One patient receiving 400mg a day suffered diarrhoea that was severe enough for the dose to be reduced. The four patients who received 600mg a day had dose-limiting toxicities including severe diarrhoea, colitis (inflammation of the colon) and cholangitis (infection of the bile duct). All the patients in the trial who had the T790M mutation remain in the trial without further progression of their disease.

"These data indicate that ASP8273 would be expected to have potential clinical benefits with fewer adverse side-effects compared to CO-1689 and AZ-9291," Dr Murakami said.

The researchers are continuing to recruit patients to the phase I dose escalation study. "We expect a recommended dose for a phase II trial to be determined soon and then we will start recruiting patients with both EGFR and T790M mutations immediately in Japan and other Asian countries. At present we are observing partial responses in patients receiving the 100mg dose and they are tolerating it well," he will conclude.

Professor Jean-Charles Soria, chair of the scientific committee for the EORTC-NCI-AACR Symposium and chair of the Drug Development Department at Gustave Roussy Cancer campus, France, commented: "ASP8273 is the fourth EGFR-mutant specific kinase inhibitor in development for NSCLC patients with acquired resistance to EGFR inhibition related to appearance of the T790M mutation. Activity is clearly promising and toxicity is in line with the anticipated mechanism of action, but numbers are small and follow-up is quite immature at present."