Re: [新聞] 智擎最新胰臟癌新藥進度已刪文

看板Stock (股票)作者IanLi (IanLi)時間11年前 (2015/01/19 14:03)推噓14(15推 1噓 29→)

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Second-Line nal-IRI (MM-398) Shows Consistent Improvement in Clinical Outcomes in Metastatic Pancreatic Cancer 移轉性胰臟癌第二線用藥，奈米化微脂體修飾抗癌妥 (nal-IRI:nanoliposomal irinotecan) MM-398在臨床上有一致性的改善 Jan 16, 2015 http://gicasym.org/ 2015 Gastrointestinal Cancers Symposium Daily News A deeper dive of data from NAPOLI-1, a randomized, controlled, open-label phase III trial conducted in patients with gemcitabine-refractory metastatic pancreatic cancer, bolsters support for use of MM-398 plus 5-fluorouracil (5-FU)/leucovorin over 5-FU/leucovorin in the second-line setting (Abstract 234). Patients who received at least 80% of planned treatment during the first 6 weeks of the study achieved a 3.8-month improvement in survival when MM-398 was added to the chemotherapy backbone, according to data presented by Li-Tzong Chen, MD, PhD, of the National Institute of Cancer Research and the National Health Research Institutes in Taiwan. 抗藥性 ( gemcitabine, 中文商品名健擇，抗腫瘤作用之核苷酸類似物) 移轉性胰臟癌三期臨床實驗，在深入分析控制組與對照組數據之後，5-fluorouracil(5-fluorouracil, 5-FU 服樂癌注射劑) 與 leucovorin(若克瘤注射液，可保護正常細胞並防止葉酸拮抗劑引起嚴重之毒性) 化學療法與增加MM-398的合併療法相比，在前六週至少 80%使用本研究規畫的處方，在增加使用MM-398一組存活期應加 3.8個月，數據來自於陳立宗領導的國家衛生研究院與癌症研究所研究計畫。 MM-398 is a nanoliposomal formulation of irinotecan encapsulated in a lipid sphere, which enables the drug to circulate longer compared with standard irinotecan. Additionally, the nanoliposomal technology is said to promote drug uptake by tumor cells, where irinotecan is then converted to its active form, SN-38. MM-398是由微脂體包覆抗癌藥irinotecan的球體結構，如此能夠延長藥物週期，並能夠增加癌細胞對藥物的吸收有效轉成活化型態的 SN-38分子。 NAPOLI-1, a pivotal trial evaluating MM-398, enrolled 417 patients with metastatic pancreatic cancer who progressed on first-line gemcitabine across 76 sites in 14 countries worldwide. Following stratification by ethnicity, Karnofsky performance status, and baseline albumin level, patients were randomly assigned in a 1:1:1 ratio to MM-398 monotherapy, 5-FU/leucovorin (control), or MM-398 plus 5-FU/leucovorin. 之前的研究畫NAPOLI-1，收納了接受過移轉性胰臟癌一線療法 (gemcitabine)，來在於14國76個點的 417位病人，透過總族和體能表現指標分類，與分析了血蛋白基線，分成MM-398單獨療法，5-FU/leucovorin療法 (控制組) 和5-FU/leucovorin結合MM-398三組。 MM-398 monotherapy fell out of favor, as it did not demonstrate superior efficacy compared with 5-FU/leucovorin and produced greater toxicity on its own than when used in combination with 5-FU/leucovorin. As such, efficacy and safety of combination treatment with MM-398 plus 5-FU/leucovorin held greater interest. MM-398單獨療法因為比常用 5-FU/leucovorin療法沒有顯著的療效優勢，且比和 5-FU/leucovorin療法合併使用毒性高而未被偏愛。但 5-FU/leucovorin療法結合MM-398後的療效和安全性引起高度興趣。 The NAPOLI-1 investigators previously reported that second-line treatment with MM-398 plus 5-FU/leucovorin significantly improved overall survival (OS), progression-free survival (PFS), and the overall response rate (ORR) and led to greater decreases in CA19-9 levels compared with 5-FU/leucovorin alone in the intent-to-treat (ITT) population. More specifically, a comparison of MM-398 plus 5-FU/leucovorin versus 5-FU/leucovorin revealed: NAPOLI-1 研究結果指出在意向分析之下 (intent-to-treat, ITT)， 5-FU/leucovorin療法結合MM-398後，在總存活期 (overall survival, OS) 與無惡化存活期 (progression- free survival, PFS) 和整體療效 (overall response rate , ORR)都有顯著改善 (significantly)，此外並降大大地低了 CA19-9腫瘤指標。達到下述成果： Median OS of 6.1 months versus 4.2 months (stratified hazard ratio [HR] 0.57; 95% CI [0.41, 0.80]; p = 0.0009) 總存活期中位數由 4.2個月改善到6.1個月 Median PFS of 3.1 months versus 1.5 months (p = 0.0001) ORR of 16% versus 1% (p < 0.001) 無惡化存活期中位數由1.5個月改善至3.1個月 At least 50% CA19-9 reduction in 36% versus 12% (p = 0.0009) CA19-9腫瘤指標降低達50%的由12%增加到36% “The Forest plot sensitivity analyses also favored the MM-398 combination over 5-FU/leucovorin across all the prognostic subanalyses,” Dr. Chen said. Variables evaluated included the stratification factors (ethnicity, Karnofsky performance status, and baseline albumin), as well as tumor location, liver metastases, disease stage at diagnosis, time since initial histological diagnosis, number of prior lines of therapy, time since last prior therapy, and CA19-9 levels. 陳博士指出：「在森林圖的敏感性分析也偏好MM-398結合5-FU /leucovorin的療法。」，在各種變數分析和病情如腫瘤位置與肝功能和病情分期與病史，之前的治療史與腫瘤指標。 New support for the ITT data comes from an analysis of the per-protocol (PP) population, defined as patients who received at least 80% of the target dose of chemotherapy in the first 6 weeks of the study and who did not violate any inclusion/exclusion criteria. The PP group for the MM-398 and control arms represents approximately 60% of patients originally assigned to these arms. Although early progression, clinical deterioration, death, and consent withdrawal accounted for some attrition, dose reductions or interruptions stemming from adverse events primarily accounted for why patients failed to make the PP group. 新的數據來自按照計劃接受分派的治療 (per-protocol, PP) 分析結果，療程定義為六週內至少施用 80%的目標劑量，沒有違反任何相容不相容的標準。MM-398和控制組，在排除之前階段中臨床惡化或死亡等原因退出，或劑量有減少或中斷，接受分派的治療尚包含 60%成員。 The more recent PP analysis of MM-398 plus 5-FU/leucovorin versus 5-FU/leucovorin alone showed a greater survival difference between groups than the original ITT analysis. Median OS in the PP subset extended to 8.9 months with MM-398 versus 5.1 months without (stratified HR 0.47; 95% CI [0.29, 0.77]; p = 0.0018). 近期的按照計劃接受分派的治療的分析顯示，MM-398結合5-FU /leucovorin複合療法相較5-FU/leucovorin單獨療法的結果比意向分析預期還好，在有結合使用MM-398，總存活期中位數由 5.1個月增加到 8.9個月。 The toxicity profile of MM-398 when added to 5-FU/leucovorin appeared manageable. In the safety population, the most frequent adverse events of grade 3 or higher occurring more often with versus without addition of MM-398 included neutropenia (20% vs. 2%), fatigue (14% vs. 4%), diarrhea (13% vs. 5%), vomiting (11% vs. 3%), and nausea (8% vs. 3%). MM-398在藥物毒性部分，與 5-FU/leucovorin並用時是能夠控制的。安全分析群體中最常見的三級以上不良反應結合MM-398 是較常發生，嗜中性白血球低下( neutropenia) 由2%增為20% ，疲倦 ( fatigue) 由4%增為 14%，腹瀉 ( diarrhea) 由 5% 增為 13%，嘔吐 (vomiting) 由3%增為 11%，反胃 (nausea) 由3%增為8%。 Discussant Laura Williams Goff, MD, of Vanderbilt University Medical Center, who reviewed the NAPOLI-1 findings, noted that MM-398 yielded “a provocative partial response rate in the second-line patient population of 16% in the combination arm,” which stacks up favorably compared with 8% partial response rates previously reported with FOLFIRI in second-line pancreatic cancer. In accord, Dr. Goff believes that MM-398 represents an exciting new option for further development in pancreas cancer. 評論家Laura Williams Goff 對NAPOLI-1結果關注到「第二線用藥的患者在結合MM-398療法 16%有強烈的反應。」相較於之前的 FOLFIRI只有8%有更好的結果。Goff博士相信MM-398能成為未來胰臟癌治療研發選擇。 MM-398 has received a Fast Track designation with the U.S. Food and Drug Administration based on its activity in combination with 5-FU/leucovorin in pancreatic cancer previously treated with gemcitabine-based therapy. MM-398由於結合 5-FU/leucovorin的療效，已經被美國食品藥物管理局 (USFDA) 批准新藥快速審查資格。 -------------------------------------------------------------------------- 心得 MM-398是屬於類新藥，主要是改善irinotecan的毒性與增加藥物在體內的療效。而在實驗數據MM-398單獨使用並不理想，屬於改善既有療法反不佳的後備療法，必須搭配 5-FU/leucovorin的化療療法，成為新的混合化療法，但不良副作用成倍數增加影響生活品質，是否有改善方法需要注意。在總存活期中位數與無惡化存活期中位數能夠增加接近一倍，算是胰臟癌治療上的一大進步，因為胰臟癌不易早期發現，而發現後一年存活率不到四分之一，五年存活率約5%，所以能延長存活期中位數數個月，也是一個治療上顯著的成效。 -- 責任聲明：本內容僅供參考，投資需審慎考量本身之需求與投資風險，吾恕不負任何法律責任，亦不作任何保證。內容數據取材於公開資訊觀測站，或各公司財務資訊專區，或相關網站資料引述；資料數據有誤請指正，並以資料出處為準，若資料內容有未盡完善之處，恕不負責。此外，非經本人同意，不得將本篇內容加以複製或轉載。 -- ※ 發信站: 批踢踢實業坊(ptt.cc), 來自: 111.243.188.228 ※ 文章網址: https://www.ptt.cc/bbs/Stock/M.1421647424.A.33E.html

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