終於有一種可以治療多數常見肺癌突變的療法


  【24drs.com】KRAS突變是最常見的非小細胞肺癌(NSCLC)致癌基因改變,影響約20%的案例,不過,不像比較少見的EGFR和ALK突變,對於KRAS突變NSCLC並沒有標靶療法。
  
  根據發表於美國臨床腫瘤協會(ASCO)2012年年會的研究,實驗性的標靶療法selumetinib或許可改變這個狀況。
  
  根據達那-法柏癌症研究治療中心的Pasi A. Janne博士指出,在第2期試驗中,該藥物顯示有活性,接受selumetinib的病患在各項數據上都優於安慰劑組。
  
  達那-法柏癌症研究治療中心應用癌症科學協同主任Janne博士在媒體聲明稿中表示,這是首次我們對KRAS突變肺癌佔此類疾病大宗的類型有了一種有效的療法。
  
  所有研究對象都是第IIIB-IV期疾病,未曾接受過化療,全部都接受selumetinib或安慰劑加上docetaxel這個標準化療。
  
  與安慰劑相比,Selumetinib顯示出較優的反應率(37% vs 0%;P< .0001)與延長的無惡化存活期間(5.3 vs 2.1個月;風險比,0.58;80%信心區間,0.42-0.79;單側P= .0138)。
  
  平均而言,Selumetinib組的病患存活較安慰劑組更久(9.4 vs. 5.2個月),但是差異未達統計上的顯著程度。
  
  研究作者指出,這是首次採用前瞻型研究顯示一種對KRAS-突變肺癌有效之標靶療法的臨床效益。
  
  在ASCO會議中,一名癌症專家贊同這項結果。耶魯癌症中心暨Smilow癌症醫院的Thomas Lynch醫師表示需要更多研究,但是這相當令人鼓舞。特別是無惡化與整體存活方面的結果,並且在當日會議重點中提到這篇研究。
  
  根據Janne博士表示,Selumetinib是目前唯一針對KRAS突變NSCLC的標靶療法,GlaxoSmithKline藥廠正在進行比較MEK抑制劑(GSK1120212)和docetaxel化療的第2期試驗。
  
  從2009年4月至2010年6月,在12國的67處中心篩檢了422名肺癌病患;113人為KRAS突變NSCLC,有87人被隨機納入試驗。
  
  作者們表示,基本的特徵是相當一致的,每個治療組約有50%的病患屬於WHO表現分數0,約50%是女性;治療週期中位數,安慰劑組為4、selumetinib組為5 。
  
  因副作用而中止的比率,selumetinib組多於安慰劑組(18.2% vs 11.9%)。嗜中性白血球減少症是最常見的血液學不良事件。
  
  Selenium組和安慰劑組的副作用
副作用 Selumetinib 安慰劑
嗜中性白血球減少症 67.4% 54.8%
發熱性嗜中白血性球減少症 15.9% 0.0%
呼吸困難 2.3% 11.9%
呼吸衰竭 6.8% 4.8%
虛弱 9.1% 0.0%

  Janne博士表示,這些臨床發現的臨床意義,除了治療肺癌,還包括其他有KRAS突變的所有癌症,如胰臟癌和大腸直腸癌。
  
  資料來源:http://www.24drs.com/professional/list/content.asp?x_idno=6855&x_classno=0&x_chkdelpoint=Y
  

Finally, a Treatment for Most Common Lung Cancer Mutation

By Nick Mulcahy
Medscape Medical News

June 14, 2012 (Chicago, Illinois) — KRAS mutations are the most common oncogenic alteration in nonsmall-cell lung cancer (NSCLC), with about 20% of cases affected. However, unlike for the less common EGFR and ALK mutations, there are no targeted therapies for KRAS-mutant NSCLC.

The experimental targeted therapy selumetinib (AstraZeneca) might change this situation, according to a presentation here at the 2012 Annual Meeting of the American Society of Clinical Oncology (ASCO).

The drug showed activity in a phase 2 trial in which patients receiving selumetinib fared better than those receiving placebo on a number of measures, according to Pasi A. Janne, MD, PhD, from the Dana-Farber Cancer Institute in Boston, Massachusetts.

"For the first time, we may have an effective treatment for KRAS-mutant lung cancer, which is the largest single subtype of the disease," said Dr. Janne in a press statement. He is scientific codirector of Dana-Farber's Belfer Institute for Applied Cancer Science.

All study participants had stage IIIB to IV disease and had received no previous chemotherapy. All received either selumetinib or placebo in addition to docetaxel, the standard chemotherapy.

Selumetinib demonstrated a superior response rate, compared with placebo (37% vs 0%; P < .0001), and prolonged progression-free survival (5.3 vs 2.1 months; hazard ratio, 0.58; 80% confidence interval, 0.42 to 0.79; 1-sided P = .0138).

The patients in the selumetinib group also survived longer, on average, than those in the placebo group (9.4 vs. 5.2 months), but the difference was not statistically significant.

This is the first prospective study to demonstrate the clinical benefit of a targeted therapy for patients with KRAS-mutant lung cancer, the study authors note.

More work is needed, but this is certainly encouraging.

At the ASCO meeting, a cancer expert endorsed the findings to date. "More work is needed, but this is certainly encouraging," said Thomas Lynch, MD, from the Yale Cancer Center and Smilow Cancer Hospital in New Haven, Connecticut. He was referring to the progression-free and overall survival findings in particular, and mentioned the study during a Highlights of the Day session.

Selumetinib is not the only targeted therapy currently being evaluated in KRAS-mutant NSCLC, according to Dr. Janne. GlaxoSmithKline is undertaking a randomized phase 2 trial comparing their MEK inhibitor (GSK1120212) with docetaxel chemotherapy, he told Medscape Medical News.

More Details

From April 2009 to June 2010, 422 lung cancer patients were screened at 67 centers in 12 countries; 113 had KRAS-mutant NSCLC and 87 were randomized into the trial.

The baseline characteristics "were balanced," the authors report. About 50% of patients in each treatment group had a WHO performance score of 0, and about 50% were female. The median number of treatment cycles was 4 in the placebo group and 5 in the selumetinib group.

Discontinuation because of adverse events was a bit worse with selumetinib than with placebo (18.2% vs 11.9%). Neutropenia was the most common hematologic adverse event.

Adverse Events in the Selenium and Placebo Groups
Adverse Event Selumetinib Placebo
Neutropenia 67.4% 54.8%
Febrile neutropenia 15.9% 0.0%
Dyspnea 2.3% 11.9%
Respiratory failure 6.8% 4.8%
Asthenia 9.1% 0.0%


These clinical findings have implications not only for the treatment of lung cancer, but for all cancers that harbor KRAS mutations, including pancreatic and colorectal cancer, said Dr. Janne.

The study was sponsored by AstraZeneca.

2012 Annual Meeting of the American Society of Clinical Oncology: Abstract 7503. Presented June 2, 2012.

    
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